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Sample records for diabetes impair gap

  1. Hyperglycaemia and diabetes impair gap junctional communication among astrocytes.

    Science.gov (United States)

    Gandhi, Gautam K; Ball, Kelly K; Cruz, Nancy F; Dienel, Gerald A

    2010-03-15

    Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15-25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20-24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

  2. Impairment of the glymphatic system after diabetes

    DEFF Research Database (Denmark)

    Jiang, Quan; Zhang, Li; Ding, Guangliang

    2017-01-01

    diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal...... to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus......The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how...

  3. Type 2 diabetes mellitus and exercise impairment.

    Science.gov (United States)

    Reusch, Jane E B; Bridenstine, Mark; Regensteiner, Judith G

    2013-03-01

    Limitations in physical fitness, a consistent finding in individuals with both type I and type 2 diabetes mellitus, correlate strongly with cardiovascular and all-cause mortality. These limitations may significantly contribute to the persistent excess cardiovascular mortality affecting this group. Exercise impairments in VO2 peak and VO2 kinetics manifest early on in diabetes, even with good glycemic control and in the absence of clinically apparent complications. Subclinical cardiac dysfunction is often present but does not fully explain the observed defect in exercise capacity in persons with diabetes. In part, the cardiac limitations are secondary to decreased perfusion with exercise challenge. This is a reversible defect. Similarly, in the skeletal muscle, impairments in nutritive blood flow correlate with slowed (or inefficient) exercise kinetics and decreased exercise capacity. Several correlations highlight the likelihood of endothelial-specific impairments as mediators of exercise dysfunction in diabetes, including insulin resistance, endothelial dysfunction, decreased myocardial perfusion, slowed tissue hemoglobin oxygen saturation, and impairment in mitochondrial function. Both exercise training and therapies targeted at improving insulin sensitivity and endothelial function improve physical fitness in subjects with type 2 diabetes. Optimization of exercise functions in people with diabetes has implications for diabetes prevention and reductions in mortality risk. Understanding the molecular details of endothelial dysfunction in diabetes may provide specific therapeutic targets for the remediation of this defect. Rat models to test this hypothesis are under study.

  4. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... experiment showed a lower dye diffusion distance of Cx46 V44M cells, ... Studies of connexins show that channel gating and permeability .... have found that connexin assembled into gap junction plaques is not soluble in 1% ..... high glucose reduces gap junction activity in microvascular endothelial cells.

  5. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    LIJUAN CHEN

    2017-12-20

    Dec 20, 2017 ... showed a lower dye diffusion distance of Cx46 V44M cells, which indicates that the gap junction intercellular ... permeability could be affected by alterations of charged residues of .... bled into gap junction plaques is not soluble in 1% Triton ..... regulation of connexin 43 expression by high glucose reduces.

  6. Impairment of the glymphatic system after diabetes.

    Science.gov (United States)

    Jiang, Quan; Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

    2017-04-01

    The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

  7. Impaired coronary microvascular function in diabetics

    International Nuclear Information System (INIS)

    Tsujimoto, Go

    2000-01-01

    Global and regional myocardial uptake was determined with technetium-99m tetrofosmin and a 4 hour exercise (370 MBq iv) and rest (740 MBq iv) protocol, in 24 patients with non-insulin dependent diabetes mellitus and in 22 control subjects. The purpose of this study was to evaluate impaired coronary microvascular function in diabetics by measurement of % uptake increase in myocardial counts. The parameter of % uptake increase (ΔMTU) was calculated as the ratio of exercise counts to rest myocardial counts with correction of myocardial uptake for dose administered and physical decay between the exercise study and the rest study. Global ΔMTU was significantly lower in the diabetics than in control subjects (14.4±5.4% vs. 21.7±8.5%, p<0.01). Regional ΔMTU in each of 4 left ventricular regions (anterior, septal, inferior, posterolateral) was significantly lower in the diabetic group than in the control group (p<0.01) respectively, but there were no significant differences between ΔMTU in the 4 left ventricular regions in the same group. ΔMTU was useful as a non-invasive means of evaluating impaired coronary microvascular function in diabetics. (author)

  8. Effects of coverage gap reform on adherence to diabetes medications.

    Science.gov (United States)

    Zeng, Feng; Patel, Bimal V; Brunetti, Louis

    2013-04-01

    To investigate the impact of Part D coverage gap reform on diabetes medication adherence. Retrospective data analysis based on pharmacy claims data from a national pharmacy benefit manager. We used a difference-in-difference-indifference method to evaluate the impact of coverage gap reform on adherence to diabetes medications. Two cohorts (2010 and 2011) were constructed to represent the last year before Affordable Care Act (ACA) reform and the first year after reform, respectively. Each patient had 2 observations: 1 before and 1 after entering the coverage gap. Patients in each cohort were divided into groups based on type of gap coverage: no coverage, partial coverage (generics only), and full coverage. Following ACA reform, patients with no gap coverage and patients with partial gap coverage experienced substantial drops in copayments in the coverage gap in 2011. Their adherence to diabetes medications in the gap, measured by percentage of days covered, improved correspondingly (2.99 percentage points, 95% confidence interval [CI] 0.49-5.48, P = .019 for patients with no coverage; 6.46 percentage points, 95% CI 3.34-9.58, P gap in 2011. However, their adherence did not increase (-0.13 percentage point, P = .8011). In the first year of ACA coverage gap reform, copayments in the gap decreased substantially for all patients. Patients with no coverage and patients with partial coverage in the gap had better adherence in the gap in 2011.

  9. Promoting Healthful Exercise for Visually Impaired Persons with Diabetes.

    Science.gov (United States)

    Weitzman, D. M.

    1993-01-01

    This article discusses the importance of exercise for many people with visual impairments and diabetes. It lists precautions for the person with visual impairments and diabetes and specifies who should not exercise, explains "diabetes-specific" benefits of exercise, suggests a format for a safe workout, and includes an example of a successful…

  10. Cognitive impairment in patients with type 2 diabetes mellitus ...

    African Journals Online (AJOL)

    Cognitive impairment in patients with type 2 diabetes mellitus: Perspectives and ... may have a deteriorating effect on mental health including a decline in cognitive ... of Diabetes; Functional Foods and Human Diet; Quality of Life and Wellness ...

  11. Diabetes mellitus and impairment of intestinal barier function

    OpenAIRE

    Hoffmanová, Iva

    2015-01-01

    Introduction: Impairment of intestinal barrier function is involved in pathogenesis of immune mediated diseases (such as type 1 diabetes mellitus or celiac disease) and metabolic diseases (such as type 2 diabetes mellitus). Aims of study: The first aim was to analyze impairment of mucosal part of intestinal barrier in both type of diabetes and to describe differences when compared to celiac disease, which is a typical condition associated with impairment of intestinal barrier function. The se...

  12. The relationship between diabetic retinopathy and cognitive impairment.

    Science.gov (United States)

    Crosby-Nwaobi, Roxanne R; Sivaprasad, Sobha; Amiel, Stephanie; Forbes, Angus

    2013-10-01

    Recent studies have shown an increased risk for cognitive impairment and dementia in patients with diabetes. An association between diabetic retinopathy (DR) and retinal microvasculature disease and cognitive impairment has been reported as potential evidence for a microvascular component to the cognitive impairment. It was hypothesized that severity of DR would be associated with cognitive impairment in individuals with type 2 diabetes. Three hundred eighty patients with type 2 diabetes were recruited from a population-based eye screening program and grouped by severity of DR as follows: no/mild DR (n=252) and proliferative diabetic retinopathy (PDR) (n=128). Each participant underwent psychosocial assessment; depression screening; ophthalmic and physical examination, including blood assays; and cognitive assessment with the Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini-Mental State Examination (MMSE), and the Mini-Cog. General linear modeling was used to examine severity of DR and cognitive impairment, adjusting for confounders. Severity of DR demonstrated an inverse relationship with cognitive impairment (fully adjusted R2=0.415, Pcognitive impairment scores on ACE-R (adjusted mean±SE 77.0±1.9) compared with the PDR group (82.5±2.2, Pcognitive impairment compared with 5% in the PDR group (n=6). Patients with minimal DR demonstrated more cognitive impairment than those with advanced DR. Therefore, the increased prevalence of cognitive impairment in diabetes may be associated with factors other than evident retinal microvascular disease.

  13. Closing anion gap without insulin in euglycaemic diabetic ketoacidosis

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2017-01-01

    Full Text Available Euglycaemic diabetic ketoacidosis (euDKA occurs in patients with poor carbohydrate intake who continue to take insulin. For these patients are not truly in the insulin-deficient state, intravenous fluid resuscitation alone can correct the ketoacidosis without any risk of hypoglycaemia. Diagnosis of euDKA can be missed in inexperienced settings; therefore, calculating anion gap and measuring ketone levels should be practiced in every sick diabetic patient regardless of glucose levels.

  14. Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Gengyin Wang

    2016-08-01

    Full Text Available Background/Aims: To explore the effects of sulforaphane (SFN on neuronal apoptosis in hippocampus and memory impairment in diabetic rats. Methods: Thirty male rats were randomly divided into normal control, diabetic model and SFN treatment groups (N = 10 in each group. Streptozotocin (STZ was applied to establish diabetic model. Water Morris maze task was applied to test learning and memory. Tunel assaying was used to detect apoptosis in hippocampus. The expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1 were detected by western blotting. Neurotrophic factor levels and AKT/GSK3β pathway were also detected. Results: Compared with normal control, learning and memory were apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1 in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic modeling. By contrast, SFN treatment prevented the memory impairment, decreased the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed diabetic modeling-induced decrease of p-Akt, p-GSK3β, NGF and BDNF expressions. Conclusion: SFN could prevent the memory impairment and apoptosis of hippocampal neurons in diabetic rat. The possible mechanism was related to the regulation of neurotropic factors and Akt/GSK3β pathway.

  15. ALENCE OF DIABETES LITUS AND IMPAIRED GLUCOSE ...

    African Journals Online (AJOL)

    Its. The crude prevalences for diabetes mellitus and IGT e 2.45% and 2.7% respectively. The age-adjusted valences using a standard world population were 4.5% nfidence interval (CI) 1.54 -7.42) and 5.1% (CI 2.45- 5.51) diabetes and IGT respectively. The prevalence of diabetes similar in male and female workers (P ...

  16. Type 1 Diabetes Mellitus and Cognitive Impairments: A Systematic Review.

    Science.gov (United States)

    Li, Wei; Huang, Edgar; Gao, Sujuan

    2017-01-01

    Type 1 diabetes mellitus (T1DM) is a major subtype of diabetes and is usually diagnosed at a young age with insulin deficiency. The life expectancy of T1DM patients has increased substantially in comparison with that three decades ago due to the availability of exogenous insulin, though it is still shorter than that of healthy people. However, the relation remains unclear between T1DM and dementia as an aging-related disease. We conducted a systematic review of existing literature on T1DM and cognition impairments by carrying out searches in electronic databases Medline, EMBASE, and Google Scholar. We restricted our review to studies involving only human subjects and excluded studies on type 2 diabetes mellitus or non-classified diabetes. A meta-analysis was first performed on the relationship between T1DM and cognitive changes in youths and adults respectively. Then the review focused on the cognitive complications of T1DM and their relation with the characteristics of T1DM, glycemic control, diabetic complications, comorbidities, and others. First, age at onset, disease duration, and glycemic dysregulation were delineated for their association with cognitive changes. Then diabetic ketoacidosis, angiopathy, and neuropathy were examined as diabetic complications for their involvement in cognitive impairments. Lastly, body mass index and blood pressure were discussed for their relations with the cognitive changes. Future studies are needed to elucidate the pathogenesis of T1DM-related cognitive impairments or dementia.

  17. Impaired peripheral nerve regeneration in type-2 diabetic mouse model.

    Science.gov (United States)

    Pham, Vuong M; Tu, Nguyen Huu; Katano, Tayo; Matsumura, Shinji; Saito, Akira; Yamada, Akihiro; Furue, Hidemasa; Ito, Seiji

    2018-01-01

    Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain. To seek its effective treatment, here we prepared a type-2 diabetic mouse model by giving mice 2 injections of streptozotocin and nicotinamide and examining the ability for nerve regeneration by using a sciatic nerve transection-regeneration model previously established by us. Seventeen weeks after the last injection, the mice exhibited symptoms of type-2 diabetes, that is, impaired glucose tolerance, decreased insulin level, mechanical hyperalgesia, and impaired sensory nerve fibers in the plantar skin. These mice showed delayed functional recovery and nerve regeneration by 2 weeks compared with young healthy mice and by 1 week compared with age-matched non-diabetic mice after axotomy. Furthermore, type-2 diabetic mice displayed increased expression of PTEN in their DRG neurons. Administration of a PTEN inhibitor at the cutting site of the nerve for 4 weeks promoted the axonal transport and functional recovery remarkably. This study demonstrates that peripheral nerve regeneration was impaired in type-2 diabetic model and that its combination with sciatic nerve transection is suitable for the study of the pathogenesis and treatment of early diabetic neuropathy. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Streptozotocin diabetes and insulin resistance impairment of ...

    African Journals Online (AJOL)

    ... insulin resistance impairment of spermatogenesis in adult rat testis: Central Vs local ... Summary: Mammalian reproduction is dynamically regulated by the pituitary ... Group 3 > Streptozotocin-insulin treated group; received a single dose IP ...

  19. Impaired insulin secretion in the spontaneous diabetes rats.

    Science.gov (United States)

    Kimura, K; Toyota, T; Kakizaki, M; Kudo, M; Takebe, K; Goto, Y

    1982-08-01

    Dynamics of insulin and glucagon secretion were investigated by using a new model of spontaneous diabetes rats produced by the repetition of selective breeding in our laboratories. The perfusion experiments of the pancreas showed that the early phase of insulin secretion to continuous stimulation with glucose was specifically impaired, although the response of the early phase to arginine was preserved. The glucose-induced insulin secretion in the nineth generation (F8) which had a more remarkably impaired glucose tolerance was more reduced than in the sixth generation (F5). No significant difference of glucagon secretion in response to arginine or norepinephrine was noted between the diabetes rats and control ones. The present data indicate that the defective insulin secretion is a primary derangement in a diabetic state of the spontaneous diabetes rat. This defect in the early phase of glucose-induced insulin secretion suggests the specific impairment of the recognition of glucose by the pancreatic beta-cells. The spontaneous diabetes rats are very useful as a model of disease for investigating pathophysiology of non-insulin dependent diabetes mellitus.

  20. Two Exercise Programs for People with Diabetes and Visual Impairment.

    Science.gov (United States)

    Dods, J.

    1993-01-01

    This article describes two programs, one in Australia and one in the United States, that teach people with diabetes and visual impairment to incorporate proper diets and exercise into their daily lives and thus to gain better control of their blood glucose levels. It also presents a basic model of an exercise regimen that clients can perform at…

  1. Frequency of Gestational diabetes mellitus and impaired glucose ...

    African Journals Online (AJOL)

    3.9 ± 2.1 respectively , p<0.001]. Conclusion: The frequency of GDM and IGT in Sudanese pregnant women is within the universal estimates and parity is an important risk factor that affects impaired glucose tolerance incidence in pregnancy. Keywords: microvascular, chemical diabetes, carbohydrate intolerance.

  2. [Prevalence of postpartum impaired glucose tolerance after gestational diabetes].

    Science.gov (United States)

    Romero Gutiérrez, Gustavo; Macias Rocha, Ana Laura; Puente Alvarez, Erika Isela

    2012-10-01

    gestational diabetes mellitus (GDM) affects 2 to 10% of pregnancies and it has been postulated as a variant of type 2 diabetes mellitus (DM2) because they share a similar pathophysioiogy. Approximately in 90% the carbohydrate intolerance resolves after pregnancy, however after 5 to 16 years after delivery women will have a risk of 17 to 63% to the development of type 2 diabetes mellitus. to determine the frequency of postpartum impaired glucose tolerance in women with previous GDM. 125 patients with diagnosis of GMD were included, general data were captured, type of control during pregnancy and complications occurred. The women were instructed to undergo a postpartum oral glucose tolerance test of 75 g and 2 h, 6 weeks after their delivery date and they were classified into five groups: normal patients, type 2 diabetes mellitus, impaired glucose tolerance, impaired fasting glucose and combined both. after follow up 13 women (10.4%) were diagnosed as DM2; 14 patients (11.2%) were classified as glucose intolerance; 16 (12.8%) were catalogued with impaired fasting glucose; 6 (4.8%) had both disorders; and 76 (60.8%) were diagnosed as healthy women. the detection with a postpartum oral glucose tolerance test is necessary for the identification of the various types of disorders of the carbohydrate metabolism including DM2.

  3. The prevalence of diabetes mellitus and impaired glucose tolerance ...

    African Journals Online (AJOL)

    The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) was determined in 479 urbanised South African blacks (141 men and 338 women) of Zulu descent selected by cluster sampling in a suburb of Durban. All subjects underwent a modified glucose tolerance test whereby fasting and 2-hour postglucose ...

  4. Syndecan-4 shedding impairs macrovascular angiogenesis in diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ran; Xie, Jun; Wu, Han; Li, Guannan; Chen, Jianzhou; Chen, Qinhua; Wang, Lian; Xu, Biao, E-mail: xubiao@medmail.com.cn

    2016-05-20

    Purpose: Syndecan-4 (synd4) is a ubiquitous heparan sulfate proteoglycan cell surface receptor that modulates cell proliferation, migration, mechanotransduction, and endocytosis. The extracellular domain of synd4 sheds heavily in acute inflammation, but the shedding of synd4 in chronic inflammation, such as diabetes mellitus (DM), is still undefined. We investigated the alterations of synd4 endothelial expression in DM and the influence of impaired synd4 signaling on angiogenesis in human umbilical vein endothelial cells (HUVECs), diabetic rats, synd4 null mice, and db/db mice. Material and methods: HUVECs were incubated with advanced glycation end products (AGEs). Western blot analysis was used to determine synd4 protein expression and ELISA was used to detect soluble synd4 fragments. The concentration of synd4 in the aortic endothelia of diabetic rats was detected by immunohistochemical staining. Aortic ring assays were performed to study the process of angiogenesis in the diabetic rats and in synd4 null and db/db mice. Recombinant adenoviruses containing the synd4 gene or null were constructed to enhance synd4 aortic expression in db/db mice. Results: Western blot analysis showed decreased expression of the synd4 extracellular domain in HUVECs, and ELISA detected increased soluble fragments of synd4 in the media. Synd4 endothelial expression in the aortas of diabetic rats was decreased. Aortic ring assay indicated impaired angiogenesis in synd4 null and db/db mice, which was partially reversed by synd4 overexpression in db/db mice. Conclusion: Synd4 shedding from vascular endothelial cells played an important role in the diabetes-related impairment of angiogenesis. -- Highlights: •Synd4 shedding from endothelial cells is accelerated under the stimulation of AGEs. •Extracellular domain of synd4 is diminished in the endothelium of DM rats. •Aortic rings of synd4 null mice showed impaired angiogenesis. •Overexpression of synd4 partly rescues macrovascular

  5. Impaired Retinal Vasodilator Responses in Prediabetes and Type 2 Diabetes

    Science.gov (United States)

    Lott, Mary E.J.; Slocomb, Julia E.; Shivkumar, Vikram; Smith, Bruce; Quillen, David; Gabbay, Robert A.; Gardner, Thomas W.; Bettermann, Kerstin

    2013-01-01

    Purpose In diabetes, endothelial dysfunction and subsequent structural damage to blood vessels can lead to heart attacks, retinopathy and strokes. However, it is unclear whether prediabetic subjects exhibit microvascular dysfunction indicating early stages of arteriosclerosis and vascular risk. The purpose of this study was to examine whether retinal reactivity may be impaired early in the hyperglycemic continuum and may be associated with markers of inflammation. Methods Individuals with prediabetes (n = 22), type 2 diabetes (n = 25) and healthy age and body composition matched controls (n = 19) were studied. We used the Dynamic Vessel Analyzer to assess retinal vasoreactivity (percent change in vessel diameter) during a flickering light stimulation. Fasting highly sensitive c-reactive protein (hs-CRP), a marker of inflammation, was measured in blood plasma. Results Prediabetic and diabetic individuals had attenuated peak vasodilator and relative amplitude changes in retinal vein diameters to the flickering light stimulus compared to healthy controls (peak dilation: prediabetic subjects 3.3 ± 1.8 %, diabetic subjects 3.3 ± 2.1% controls 5.6 ± 2.6%, p = .001; relative amplitude: prediabetic subjects 4.3 ± 2.2%, diabetic subjects 5.0 ± 2.6% and control subjects 7.2 ± 3.2%, p = .003). Similar findings were observed in retinal arteries. Levels of hs-CRP were not associated with either retinal vessel response parameters. Conclusion Retinal reactivity was impaired in prediabetic and type 2 diabetic individuals in parallel with reduced insulin sensitivity but not associated with levels of hs-CRP. Retinal vasoreactivity measurements may be a sensitive tool to assess early vascular risk. PMID:23742315

  6. Diabetes mellitus and impaired glucose tolerance in urban adult population

    Directory of Open Access Journals (Sweden)

    Walter Rodrigues Júnior

    2014-01-01

    Full Text Available Objective: Estimating the prevalence of diabetes mellitus (DM and impaired glucose tolerance (IGT in the urban population aged between 30 and 69 years in the municipality of Campo Grande, state of Mato Grosso do Sul, Brazil. Methods: Population-based cross-sectional study conducted between October/2009 and February/2011. The investigation included the determination of fasting glucose and participants with blood glucose ≥ 200 mg/dL were considered diabetic. Nondiabetic patients, which showed blood glucose ≥ 100 mg/dL and < 200 mg/dL, underwent an oral glucose tolerance test (OGTT to investigate whether they had DM or IGT. Results: 1.429 individuals participated in this investigation. The general prevalence, adjusted for sex and age, were: 12.3% for DM (95%CI: 10.5 to 13.9% and 7.1% for IGT (95%CI: 5.7 to 8.4%. There was a higher prevalence of DM with increasing age in people with low educational level, family history of diabetes, overweight, obesity and central obesity. Among diabetic patients (n = 195, 25% were unaware they had the disease and were diagnosed through investigation. Among patients who already knew they had DM (n = 146, 37% were unaware of the potential chronic complications. Conclusion: This study confirms the increased prevalence of DM in Brazil and emphasizes the need for early diagnosis, as well as the importance of strict adherence to medical treatment in order to prevent its much feared complications.

  7. Why is coronary collateral growth impaired in type II diabetes and the metabolic syndrome?

    Science.gov (United States)

    Rocic, Petra

    2012-01-01

    Type II diabetes and the metabolic syndrome are strong predictors of severity of occlusive coronary disease and poorer outcomes of coronary revascularization therapies. Coronary collateral growth can provide an alternative or accessory pathway of revascularization. However, collateral growth is impaired in type II diabetes and the metabolic syndrome. Although many factors necessary for collateral growth are known and many interventions have shown promising results in animal studies, not a single attempt to induce coronary collateral growth in human clinical trials has led to satisfactory results. Accordingly, the first part of this review outlines the known deleterious effects of diabetes and the metabolic syndrome on factors necessary for collateral growth, including pro-angiogenic growth factors, endothelial function, the redox state of the coronary circulation, intracellular signaling, leukocytes and bone marrow-derived progenitors cells. The second section highlights the gaps in our current knowledge of how these factors interact with the radically altered environment of the coronary circulation in diabetes and the metabolic syndrome. The interplay between these pathologies and inadequately explored areas related to the temporal regulation of collateral remodeling and the roles of the extracellular matrix, vascular cell phenotype and pro-inflammatory cytokines are emphasized with implications to development of efficient therapies. PMID:22342811

  8. Subjective sleep impairment in adults with type 1 or type 2 diabetes : Results from Diabetes MILES-The Netherlands

    NARCIS (Netherlands)

    Nefs, Giesje; Donga, Esther; van Someren, Eus; Bot, Mariska; Speight, Jane; Pouwer, François

    AIMS: Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of

  9. Subjective sleep impairment in adults with type 1 or type 2 diabetes: Results from Diabetes MILES-The Netherlands

    NARCIS (Netherlands)

    Nefs, G.; Donga, E.; van Someren, E.J.W.; Bot, M.; Speight, J.; Pouwer, F.

    2015-01-01

    Aims: Despite growing recognition of the impact of sleep on diabetes, a clear profile of people with diabetes regarding subjective sleep impairment has yet to be established. This study examines: (1) subjective sleep characteristics in adults with type 1 and type 2 diabetes; (2) the relationship of

  10. The predictors of exercise capacity impairment in diabetic patients

    Directory of Open Access Journals (Sweden)

    Florina Frîngu

    2017-05-01

    Full Text Available Background. The exercise capacity is a key issue in a diabetic patient’s management, due to its well-known beneficial effects in terms of glycemic control, cardiovascular risk reduction and quality of life improvement. However the exercise capacity of diabetic patients is decreased many times and its determinants are sometimes less known. Our study aimed to assess the effort capacity in a cohort of diabetic patients and to find the main causative factors of its impairment. Method: 61 patients with type-2 diabetes mellitus were enrolled and underwent and transthoracic echocardiography and a cycloergometer exercise testing. Exercise performance was calculated and the influence of clinical data and ultrasound parameters was assessed. Sedentary status of each patient was established from total time/week of at least moderate physical activity. Results: the study group consisted of 48.4 % women, mean age 61.4 (±8.4 years. Disease median duration was 5 years and 21.3 % of the patients presented neuropathy, 4.5 % retinopathy and 6.5 % nephropathy. Exercise capacity was moderately and severe decreased (<5 METs in 37.7 % of patients and in this subgroup the diastolic dysfunction, sedentary behavior and old age has a significantly higher prevalence. Interestingly, by multivariate regression, the sedentary lifestyle was the main determinant of decreased effort capacity (beta-coefficient 1.37, p<0.001, suggesting the potential benefits of physical training in these patients. Conclusion. Our study found a decreased effort capacity in at least one third of the patients and this is mainly due to sedentary lifestyle and deconditioning, the diastolic dysfunction also contributes to decreased effort capacity in diabetic patients.

  11. [Cardiac risk profile in diabetes mellitus and impaired fasting glucose].

    Science.gov (United States)

    Schaan, Beatriz D'Agord; Harzheim, Erno; Gus, Iseu

    2004-08-01

    Mortality of diabetic patients is higher than that of the population at large, and mainly results from cardiovascular diseases. The purpose of the present study was to identify the prevalence of cardiovascular risk factors in subjects with diabetes mellitus (DM) or abnormal fasting glucose (FG) in order to guide health actions. A population-based cross-sectional study was carried out in a representative random cluster sampling of 1,066 adult urban population (> or =20 years) in the state of Rio Grande do Sul between 1999 and 2000. A structured questionnaire on coronary risk factors was applied and sociodemographic characteristics of all adults older than 20 years living in the same dwelling were collected. Subjects were clinically evaluated and blood samples were obtained for measuring total cholesterol and fasting glycemia. Statistical analysis was performed using Stata 7 and a 5% significance level was set. Categorical variables were compared by Pearson's chi-square and continuous variables were compared using Student's t-test or Anova and multivariate analysis, all controlled for the cluster effect. Of 992 subjects, 12.4% were diabetic and 7.4% had impaired fasting glucose. Among the risk factors evaluated, subjects who presented any kind of glucose homeostasis abnormality were at a higher prevalence of obesity (17.8, 29.2 and 35.3% in healthy subjects, impaired fasting glucose and DM respectively, pfasting glucose and DM, respectively, pfasting glucose and DM respectively, p=0.01). Subjects with any kind of glucose homeostasis abnormality represent a group, which preventive individual and population health policies should target since they have higher prevalence of coronary artery disease risk factors.

  12. Action on diabetic macular oedema: achieving optimal patient management in treating visual impairment due to diabetic eye disease.

    Science.gov (United States)

    Gale, R; Scanlon, P H; Evans, M; Ghanchi, F; Yang, Y; Silvestri, G; Freeman, M; Maisey, A; Napier, J

    2017-05-01

    This paper identifies best practice recommendations for managing diabetes and sight-threatening diabetic eye disease. The authors provide an update for ophthalmologists and allied healthcare professionals on key aspects of diabetes management, supported by a review of the pertinent literature, and recommend practice principles for optimal patient management in treating visual impairment due to diabetic eye disease. In people with diabetes, early optimal glycaemic control reduces the long-term risk of both microvascular and macrovascular complications. The authors propose more can and should be done to maximise metabolic control, promote appropriate behavioural modifications and encourage timely treatment intensification when indicated to ameliorate diabetes-related complications. All people with diabetes should be screened for sight-threatening diabetic retinopathy promptly and regularly. It is shown that attitudes towards treatment adherence in diabetic macular oedema appear to mirror patients' views and health behaviours towards the management of their own diabetes. Awareness of diabetic macular oedema remains low among people with diabetes, who need access to education early in their disease about how to manage their diabetes to delay progression and possibly avoid eye-related complications. Ophthalmologists and allied healthcare professionals play a vital role in multidisciplinary diabetes management and establishment of dedicated diabetic macular oedema clinics is proposed. A broader understanding of the role of the diabetes specialist nurse may strengthen the case for comprehensive integrated care in ophthalmic practice. The recommendations are based on round table presentations and discussions held in London, UK, September 2016.

  13. Evidence for Consistency of the Glycation Gap in Diabetes

    OpenAIRE

    Nayak, Ananth U.; Holland, Martin R.; Macdonald, David R.; Nevill, Alan; Singh, Baldev M.

    2011-01-01

    OBJECTIVE Discordance between HbA1c and fructosamine estimations in the assessment of glycemia is often encountered. A number of mechanisms might explain such discordance, but whether it is consistent is uncertain. This study aims to coanalyze paired glycosylated hemoglobin (HbA1c)-fructosamine estimations by using fructosamine to determine a predicted HbA1c, to calculate a glycation gap (G-gap) and to determine whether the G-gap is consistent over time. RESEARCH DESIGN AND METHODS We include...

  14. [Recombinant human gapM1 expressed in Pichia pastoris and its anti-diabetic effect].

    Science.gov (United States)

    Mei, Xiang; Du, Renqian; Li, Xi; Huang, Haiyan; Yu, Min; Tang, Qiqun

    2009-08-01

    Adiponectin is an adipokine predominantly synthesized and secreted by adipocytes in the white adipose tissue, and it can lower the blood glucose level and increase free fatty acid oxidation. In the current study, we developed the globular domain of adiponectin (gapM1) to treat type II diabetes. In both flask and fermentor, we cultivated Pichia pastoris expressing recombinant gapM1 and established the purification procedure by using gel filtration and anion exchange chromatography. To evaluate the biological activity of recombinant gapM1, we used rat type II diabetes model fed high-fat diet in combination with low-dose STZ (Streptozocin) induction. We purified 200 mg gapM1 with purity of 96% from 10 liters of supernatant. The recombinant gapM1 significantly lowered blood glucose (34.2%), serum triglyceride (79.6%) and total cholesterol (62.1%) in type II diabetes induced rat. Therefore, the recombinant human gapM1 is successfully expressed in Pichia pastoris and effectively treated type II diabetes in rat models.

  15. Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes.

    Science.gov (United States)

    Chen, M-C; Sheu, J-J; Wang, P-W; Chen, C-Y; Kuo, M-C; Hsieh, C-J; Chen, J-F; Chang, H-W

    2009-02-01

    This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia. Seventy-four patients were classified into four groups: Type 2 diabetic (n = 21) and non-diabetic patients (n = 10) with critical leg ischaemia and Type 2 diabetic patients without lower extremity vascular disease (n = 30) and healthy subjects (n = 13). The number and functional activity of circulating and cultured EPCs were determined. The migratory function of cultured EPCs was significantly impaired in diabetic patients without (median, 48, interquartile range, 46, 49 count/view/well) and with (median, 51, interquartile range, 46, 60 count/view/well) critical leg ischaemia and non-diabetic patients with critical leg ischaemia (median, 49, interquartile range, 47, 55 count/view/well) compared with healthy subjects (median, 63, interquartile range, 57, 65 count/view/well) (P interquartile range, 1600, 6600/10(6) cytometric events) than Type 2 diabetic patients with critical leg ischaemia (median, 5300, interquartile range, 2400, 11,100/10(6) cytometric events), non-diabetic patients with critical leg ischaemia (median, 5550, interquartile range, 2000, 32,100/10(6) cytometric events) and healthy subjects (median, 5400, interquartile range, 2700, 8700/10(6) cytometric events) (P = 0.413). The migratory function of EPCs is impaired in patients with Type 2 diabetes, even in those without critical leg ischaemia. These findings present an important new insight into the pathogenesis of impaired neovascularization and critical limb ischaemia in diabetic patients and provide avenues of future clinical study.

  16. Effects on Glycemic Control in Impaired Wound Healing in Spontaneously Diabetic Torii (SDT) Fatty Rats.

    Science.gov (United States)

    Katsuhiro, Miyajima; Hui Teoh, Soon; Yamashiro, Hideaki; Shinohara, Masami; Fatchiyah, Fatchiyah; Ohta, Takeshi; Yamada, Takahisa

    2018-02-01

    Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing. Male SDT fatty rats at 15 weeks of age were administered orally with sodium glucose co-transporter (SGLT) 2 inhibitor for 3 weeks. Wounds were induced at 2 weeks after SGLT 2 inhibitor treatment, and the wound areas were periodically examined in morphological and histological analyses. The SDT fatty rats showed a delayed wound healing as compared with the normal rats, but a glycemic control improved the impaired wound healing. In histological analysis in the skin of SDT fatty rats showed severe infiltration of inflammatory cell, hemorrhage and many bacterial masses in the remaining and slight fibrosis of crust on skin tissue . Thought that this results skin performance to be a delay of crust formation and regeneration of epithelium; however, these findings were ameliorated in the SGLT 2 inhibitor treated group. Glycemic control is effective for treatment in diabetic wounds and the SDT fatty rat may be useful to investigate pathophysiological changes in impaired diabetic wound healing.

  17. Cerebral microbleeds, cognitive impairment, and MRI in patients with diabetes mellitus.

    Science.gov (United States)

    Zhou, Hong; Yang, Juan; Xie, Peihan; Dong, Yulan; You, Yong; Liu, Jincai

    2017-07-01

    Cerebral microbleeds (CMBs), a typical imaging manifestation marker of sporadic cerebral small vessel disease, play a critical role in vascular cognitive impairment, which is often accompanied by diabetes mellitus (DM). Hence, CMBs may, in part, be responsible for the occurrence and development of cognitive impairment in patients with diabetes. Novel magnetic resonance imaging (MRI) sequences, such as susceptibility-weighted imaging and T2*-weighted gradient-echo, have the capability of noninvasively revealing CMBs in the brain. Moreover, a correlation between CMBs and cognitive impairment in patients with diabetes has been suggested in applications of functional MRI (fMRI). Since pathological changes in the brain occur prior to observable decline in cognitive function, neuroimaging may help predict the progression of cognitive impairment in diabetic patients. In this article, we review the detection of CMBs using MRI in diabetic patients exhibiting cognitive impairment. Future studies should emphasize the development and establishment of a novel MRI protocol, including fMRI, for diabetic patients with cognitive impairment to detect CMBs. A reliable MRI protocol would also be helpful in understanding the pathological mechanisms of cognitive impairment in this important patient population. Copyright © 2017. Published by Elsevier B.V.

  18. High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

    Science.gov (United States)

    Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

    2015-01-01

    The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

  19. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes.

    NARCIS (Netherlands)

    Manschot, S.M.; Brands, A.M.; Grond, J. van der; Kessels, R.P.C.; Algra, A.; Kappelle, L.J.; Biessels, G.J.

    2006-01-01

    The structural correlates of impaired cognition in type 2 diabetes are unclear. The present study compared cognition and brain magnetic resonance imaging (MRI) between type 2 diabetic patients and nondiabetic control subjects and assessed the relationship between cognition and MRI findings and blood

  20. Risk scores for diabetes and impaired glycaemia in the Middle East and North Africa

    DEFF Research Database (Denmark)

    Handlos, Line Neerup; Witte, Daniel Rinse; Almdal, Thomas Peter

    2013-01-01

    AIMS: To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk...

  1. Long-term changes in retinal vascular diameter and cognitive impairment in type 1 diabetes.

    Science.gov (United States)

    Nunley, Karen A; Metti, Andrea L; Klein, Ronald; Klein, Barbara E; Saxton, Judith A; Orchard, Trevor J; Costacou, Tina; Aizenstein, Howard J; Rosano, Caterina

    2018-05-01

    To assess associations between cognitive impairment and longitudinal changes in retinal microvasculature, over 18 years, in adults with type 1 diabetes. Participants of the Pittsburgh Epidemiology of Diabetes Complications Study received ≥3 fundus photographs between baseline (1986-1988) and time of cognitive assessment (2010-2015: N = 119; 52% male; mean age and type 1 diabetes duration 43 and 34 years, respectively). Central retinal arteriolar equivalent and central retinal venular equivalent were estimated via computer-based methods; overall magnitude and speed of narrowing were quantified as cumulative average and slope, respectively. Median regression models estimated associations of central retinal arteriolar equivalent and central retinal venular equivalent measures with cognitive impairment status, adjusted for type 1 diabetes duration. Interactions with HbA1c, proliferative retinopathy and white matter hyperintensities were assessed. Compared with participants without cognitive impairment, those with clinically relevant cognitive impairment experienced 1.8% greater and 31.1% faster central retinal arteriolar equivalent narrowing during prior years (t = -2.93, p = 0.004 and t = -3.97, p impairment. Long-term arterial retinal changes could indicate type 1 diabetes-related cognitive impairment. Studies examining longitudinal central retinal arteriolar equivalent changes as early biomarkers of cognitive impairment risk are warranted.

  2. Undiagnosed cognitive impairment, health status and depressive symptoms in patients with type 2 diabetes

    NARCIS (Netherlands)

    Koekkoek, Paula S.; Biessels, Geert Jan; Kooistra, Minke; Janssen, Jolien; Kappelle, L. Jaap; Rutten, Guy E H M

    2015-01-01

    Aims Type 2 diabetes (T2DM) is associated with cognitive impairment. We examined whether undiagnosed cognitive impairment in T2DM-patients is associated with a reduced health status and depressive symptoms. Methods In an observational study, 225 T2DM-patients aged < 70 years were examined at their

  3. Role of inflammatory markers in Elderly Type 2 Diabetic Patients with Mild Cognitive Impairment.

    Science.gov (United States)

    Hosny, Salwa S; Bahaaeldin, Ahmed M; Khater, Mohamed S; Bekhet, Meram M; Hebah, Hayam A; Hasanin, Ghada A

    2018-04-22

    Type 2 diabetes (T2DM) is a risk factor for Alzheimer's disease and mild cognitive impairment. The etiology of cognitive impairment in people with T2DM is uncertain but, chronic hyperglycemia, cerebral micro vascular disease, severe hypoglycemia, and increased prevalence of macro vascular disease are implicated. to determine the serum levels of soluble vascular adhesion molecule (sVCAM-1) and highly sensitive C-reactive protein (hs-CRP) in elderly type 2 diabetics with mild cognitive impairment (MCI). Our study was conducted on 90 elderly subjects (aged 60 years old or more). They were divided into Group І, 30 patients with T2DM and mild cognitive impairment, group ІІ, 30 patients with T2DM without cognitive impairment and group III, 30 healthy subjects as a control group. They were subjected to history taking, full clinical examination, anthropometric measurement, the Addenbrooke's Cognitive Examination III (ACE---III 2012), Fasting plasma glucose, 2 hours plasma glucose, HbA1c, lipid profile, protein/creatinine ratio, serum sVCAM-1 and hs-CRP. Serum levels of sVCAM-1 in diabetic elderly patients with MCI were significantly higher (946.7 ± 162.01 ng/ml) than diabetic elderly patients without cognitive impairment (479.06 ± 65.27 ng/ml) and control (263.7 ± 72.05 ng/ml) with (P=0.002). Serum levels of Hs-CRP in diabetic elderly patients with MCI were significantly higher than as diabetic elderly patients without cognitive impairment and control with (P=0.005). Elderly diabetic patients with mild cognitive impairment, have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation than other groups. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Chronically impaired autoregulation of cerebral blood flow in long-term diabetics

    DEFF Research Database (Denmark)

    Bentsen, N; Larsen, B; Lassen, N A

    1975-01-01

    Using the arteriovenous oxygen difference method autoregulation of cerebral blood flow (CBF) was tested in 16 long-term diabetics and eight control patients. Blood pressure was raised by angiotensin infusion and lowered by trimethaphan camsylate infusion, in some cases combined with head-up tilting...... of the patient. Regression analysis was carried out on the results in order to quantify autoregulatory capacity. In the control patients CBF did not vary with moderate blood pressure variations, indicating normal autoregulation. In four of the 16 diabetic patients CBF showed significant pressure dependency......, indicating impaired autoregulation. The cause of impaired autoregulation in some long-term diabetics is believed to be diffuse or multifocal dysfunction of cerebral arterioles due to diabetic vascular disease. Other conditions with impaired autoregulation are discussed and compared with that seen in long...

  5. cAMP-dependent Protein Kinase (PKA) Signaling Is Impaired in the Diabetic Heart.

    Science.gov (United States)

    Bockus, Lee B; Humphries, Kenneth M

    2015-12-04

    Diabetes mellitus causes cardiac dysfunction and heart failure that is associated with metabolic abnormalities and autonomic impairment. Autonomic control of ventricular function occurs through regulation of cAMP-dependent protein kinase (PKA). The diabetic heart has suppressed β-adrenergic responsiveness, partly attributable to receptor changes, yet little is known about how PKA signaling is directly affected. Control and streptozotocin-induced diabetic mice were therefore administered 8-bromo-cAMP (8Br-cAMP) acutely to activate PKA in a receptor-independent manner, and cardiac hemodynamic function and PKA signaling were evaluated. In response to 8Br-cAMP treatment, diabetic mice had impaired inotropic and lusitropic responses, thus demonstrating postreceptor defects. This impaired signaling was mediated by reduced PKA activity and PKA catalytic subunit content in the cytoplasm and myofilaments. Compartment-specific loss of PKA was reflected by reduced phosphorylation of discrete substrates. In response to 8Br-cAMP treatment, the glycolytic activator PFK-2 was robustly phosphorylated in control animals but not diabetics. Control adult cardiomyocytes cultured in lipid-supplemented media developed similar changes in PKA signaling, suggesting that lipotoxicity is a contributor to diabetes-induced β-adrenergic signaling dysfunction. This work demonstrates that PKA signaling is impaired in diabetes and suggests that treating hyperlipidemia is vital for proper cardiac signaling and function. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. cAMP-dependent Protein Kinase (PKA) Signaling Is Impaired in the Diabetic Heart*

    Science.gov (United States)

    Bockus, Lee B.; Humphries, Kenneth M.

    2015-01-01

    Diabetes mellitus causes cardiac dysfunction and heart failure that is associated with metabolic abnormalities and autonomic impairment. Autonomic control of ventricular function occurs through regulation of cAMP-dependent protein kinase (PKA). The diabetic heart has suppressed β-adrenergic responsiveness, partly attributable to receptor changes, yet little is known about how PKA signaling is directly affected. Control and streptozotocin-induced diabetic mice were therefore administered 8-bromo-cAMP (8Br-cAMP) acutely to activate PKA in a receptor-independent manner, and cardiac hemodynamic function and PKA signaling were evaluated. In response to 8Br-cAMP treatment, diabetic mice had impaired inotropic and lusitropic responses, thus demonstrating postreceptor defects. This impaired signaling was mediated by reduced PKA activity and PKA catalytic subunit content in the cytoplasm and myofilaments. Compartment-specific loss of PKA was reflected by reduced phosphorylation of discrete substrates. In response to 8Br-cAMP treatment, the glycolytic activator PFK-2 was robustly phosphorylated in control animals but not diabetics. Control adult cardiomyocytes cultured in lipid-supplemented media developed similar changes in PKA signaling, suggesting that lipotoxicity is a contributor to diabetes-induced β-adrenergic signaling dysfunction. This work demonstrates that PKA signaling is impaired in diabetes and suggests that treating hyperlipidemia is vital for proper cardiac signaling and function. PMID:26468277

  7. Current Status of Clinical and Experimental Researches on Cognitive Impairment in Diabetes

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This article reviews the clinical and experimental researches on cognitive impairment related to diabetes in the recent decade. Most clinical studies indicate that the cognitive impairment in patients with type 1 diabetes mellitus is related to recurrent hypoglycemia closely. There is little research about whether or not hyperglycemia is related to cognitive impairment in patients with type 1 diabetes mellitus. Most studies indicate that the cognitive impairment in type 2 diabetes involves multiple factors through multiple mechanisms, including blood glucose, blood lipid, blood pressure, level of insulin, medication, chronic complication, etc. But, there has been no large-scale, multi-center, randomized controlled clinical trial in China recently. And what is more, some problems exist in this field of research, such as the lack of golden criterion of cognitive function measurement, different population of studied objects, and incomprehensive handling of confounding factors. Experimental studies found that hippocampal long-term potentiation (LTP) was impaired,which were manifested by impairment of spatial memory and decreased expression of LTP, but its relation to hyperglycemia, the duration of diabetes, learning and memory has always been differently reported by different researches. Thus, there are a lot of unknown things to be explored and studied in order to clarify its mechanism. TCM has abundant clinical experience in treating cerebral disease with medicine that enforces the kidney and promotes wit. However, there has been no research on treating diabetic cognitive impairment,which requires work to be done actively and TCM to be put into full play, in order to improve the treatment of diabetes and enhance living quality of patients.

  8. Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Gaster, Michael; Nehlin, Jan O; Minet, Ariane D

    2012-01-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. Recent research has shown that diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also been shown both in insulin resistant offspring of T2D patients...... and exercising T2D patients in vivo. This review will discuss the latest advances in the understanding of the molecular mechanisms regulating the TCA cycle with focus on possible underlying mechanism which could explain the impaired TCA flux in insulin resistant human skeletal muscle in type 2 diabetes....... A reduced TCA is both a marker and a maker of the diabetic phenotype....

  9. Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

    DEFF Research Database (Denmark)

    Jensen, T; Richter, Erik; Feldt-Rasmussen, Bo

    1988-01-01

    To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal...... were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy...... or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established....

  10. Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

    Science.gov (United States)

    Domínguez, R O; Pagano, M A; Marschoff, E R; González, S E; Repetto, M G; Serra, J A

    2014-01-01

    Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  11. Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-01-01

    Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

  12. Association of Sympathovagal Imbalance With Cognitive Impairment in Type 2 Diabetes in Adults.

    Science.gov (United States)

    Auroprajna, Pal; Naik, Basanta Manjari; Sahoo, Jaya Prakash; Keerthi, Gorantla Shravya; Pavanya, Manohar; Pal, Gopal Krushna

    2018-02-01

    Sympathovagal imbalance (SVI) has been reported to be associated with metabolic derangements in type 2 diabetes. We investigated the association of SVI with cognitive impairment in patients with type 2 diabetes. Patients with a new diagnosis of type 2 diabetes (n=43) and age-matched healthy control subjects (n=43) were recruited for the study. Body mass index and blood pressure measurements were recorded. SVI was assessed by spectral analysis of heart rate variability (HRV), and cognitive function was assessed by recording the positive wave that appears in 300 milliseconds from application of stimulus in event-related potential tracing (P300). Insulin resistance was determined by the homeostatic model assessment of insulin resistance (HOMA-IR) formula using blood glucose and insulin data, and oxidative stress was assessed by estimation of malondialdehyde. Association of various factors with cognitive impairment was evaluated by Pearson correlation analysis, and independent contributions of these factors to cognitive impairment were assessed by multiple regression analysis. P300 latency was significantly prolonged in the diabetes group compared with the control group. Ratio of low-frequency to high-frequency power (LF-HF ratio) of HRV, the marker of SVI was found to be significantly correlated and linked with P300. Malondialdehyde and HOMA-IR were correlated with LF-HF ratio. Treatment-naïve patients with type 2 diabetes have SVI and considerable cognitive impairment. Insulin resistance and oxidative stress contribute to cognitive impairment, and SVI could be the physiologic link to cognitive impairment in treatment-naïve patients with type 2 diabetes. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  13. Diabetes and Periodontitis – Role in Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Shikha Sharma

    2018-01-01

    Full Text Available >Introduction: The global burden of dementia, diabetes, and periodontitis is rapidly increasing and is becoming a serious area of concern. The incidence of diabetes and periodontitis usually increases in middle age, and because they share a bidirectional relationship, they are known to worsen if not controlled. Evidence suggests that the people who have diabetes are at a significant risk of developing dementia and in the last two decades, periodontitis has been increasingly linked with dementia. Currently, there is no definitive treatment of dementia.The Hypothesis: The patients who have uncontrolled diabetes with moderate-to-severe periodontal disease may be at a greater risk for developing neurodegeneration associated with dementia.Evaluation of the Hypothesis: The chronic effects of both periodontitis and diabetes may have an uncontrollable additive effect on the body of an aging individual. Immunosenescence may add to the complexity of such effects and in such a scenario, the complete resolution of the systemic inflammation or other interrelated process responsible for directly or indirectly triggering neurodegeneration may be compromised. We have proposed various interrelated mechanisms linking diabetes and periodontitis that may be amplified in an aging individual. These mechanisms may contribute to the neurodegeneration associated with dementia. Oral cavity is a major unbarred window into the systemic environment of an individual. Treatment and maintenance therapy for periodontitis on a routine basis may help reduce a significant amount of inflammatory load, especially in the diabetic population, who are at a greater risk for the future development of dementia.

  14. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Science.gov (United States)

    Westerweel, Peter E; Teraa, Martin; Rafii, Shahin; Jaspers, Janneke E; White, Ian A; Hooper, Andrea T; Doevendans, Pieter A; Verhaar, Marianne C

    2013-01-01

    Circulating Endothelial Progenitor Cell (EPC) levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment. Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+)Flk-1(+) EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+) hematopoietic progenitor cells (HPC) and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed. In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro. EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  15. Impaired endothelial progenitor cell mobilization and dysfunctional bone marrow stroma in diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Peter E Westerweel

    Full Text Available Circulating Endothelial Progenitor Cell (EPC levels are reduced in diabetes mellitus. This may be a consequence of impaired mobilization of EPC from the bone marrow. We hypothesized that under diabetic conditions, mobilization of EPC from the bone marrow to the circulation is impaired -at least partly- due to dysfunction of the bone marrow stromal compartment.Diabetes was induced in mice by streptozotocin injection. Circulating Sca-1(+Flk-1(+ EPC were characterized and quantified by flow cytometry at baseline and after mobilization with G-CSF/SCF injections. In vivo hemangiogenic recovery was tested by 5-FU challenge. Interaction within the bone marrow environment between CD34(+ hematopoietic progenitor cells (HPC and supporting stroma was assessed by co-cultures. To study progenitor cell-endothelial cell interaction under normoglycemic and hyperglycemic conditions, a co-culture model using E4Orf1-transfected human endothelial cells was employed.In diabetic mice, bone marrow EPC levels were unaffected. However, circulating EPC levels in blood were lower at baseline and mobilization was attenuated. Diabetic mice failed to recover and repopulate from 5-FU injection. In vitro, primary cultured bone marrow stroma from diabetic mice was impaired in its capacity to support human CFU-forming HPC. Finally, hyperglycemia hampered the HPC supportive function of endothelial cells in vitro.EPC mobilization is impaired under experimental diabetic conditions and our data suggest that diabetes induces alterations in the progenitor cell supportive capacity of the bone marrow stroma, which could be partially responsible for the attenuated EPC mobilization and reduced EPC levels observed in diabetic patients.

  16. Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

    DEFF Research Database (Denmark)

    Jensen, T; Richter, E A; Feldt-Rasmussen, B

    1988-01-01

    To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal...... urinary albumin excretion (less than 30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion greater than 300 mg/24 h). Ten non-diabetic subjects matched for sex...... were not explained by differences in metabolic control or the degree of autonomic neuropathy. Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy...

  17. The Impact of Microbiota-Gut-Brain Axis on Diabetic Cognition Impairment

    Directory of Open Access Journals (Sweden)

    Youhua Xu

    2017-04-01

    Full Text Available Progressive cognitive dysfunction is a central characteristic of diabetic encephalopathy (DE. With an aging population, the incidence of DE is rising and it has become a major threat that seriously affects public health. Studies within this decade have indicated the important role of risk factors such as oxidative stress and inflammation on the development of cognitive impairment. With the recognition of the two-way communication between gut and brain, recent investigation suggests that “microbiota-gut-brain axis” also plays a pivotal role in modulating both cognition function and endocrine stability. This review aims to systemically elucidate the underlying impact of diabetes on cognitive impairment.

  18. Pathogenesis and treatment of impaired wound healing in diabetes mellitus: new insights.

    Science.gov (United States)

    Baltzis, Dimitrios; Eleftheriadou, Ioanna; Veves, Aristidis

    2014-08-01

    Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes mellitus, as wound healing is impaired in the diabetic foot. Wound healing is a dynamic and complex biological process that can be divided into four partly overlapping phases: hemostasis, inflammation, proliferative and remodeling. These phases involve a large number of cell types, extracellular components, growth factors and cytokines. Diabetes mellitus causes impaired wound healing by affecting one or more biological mechanisms of these processes. Most often, it is triggered by hyperglycemia, chronic inflammation, micro- and macro-circulatory dysfunction, hypoxia, autonomic and sensory neuropathy, and impaired neuropeptide signaling. Research focused on thoroughly understanding these mechanisms would allow for specifically targeted treatment of diabetic foot ulcers. The main principles for DFU treatment are wound debridement, pressure off-loading, revascularization and infection management. New treatment options such as bioengineered skin substitutes, extracellular matrix proteins, growth factors, and negative pressure wound therapy, have emerged as adjunctive therapies for ulcers. Future treatment strategies include stem cell-based therapies, delivery of gene encoding growth factors, application of angiotensin receptors analogs and neuropeptides like substance P, as well as inhibition of inflammatory cytokines. This review provides an outlook of the pathophysiology in diabetic wound healing and summarizes the established and adjunctive treatment strategies, as well as the future therapeutic options for the treatment of DFUs.

  19. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice.

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    Savita Khanna

    2010-03-01

    Full Text Available Chronic inflammation is a characteristic feature of diabetic cutaneous wounds. We sought to delineate novel mechanisms involved in the impairment of resolution of inflammation in diabetic cutaneous wounds. At the wound-site, efficient dead cell clearance (efferocytosis is a pre-requisite for the timely resolution of inflammation and successful healing.Macrophages isolated from wounds of diabetic mice showed significant impairment in efferocytosis. Impaired efferocytosis was associated with significantly higher burden of apoptotic cells in wound tissue as well as higher expression of pro-inflammatory and lower expression of anti-inflammatory cytokines. Observations related to apoptotic cell load at the wound site in mice were validated in the wound tissue of diabetic and non-diabetic patients. Forced Fas ligand driven elevation of apoptotic cell burden at the wound site augmented pro-inflammatory and attenuated anti-inflammatory cytokine response. Furthermore, successful efferocytosis switched wound macrophages from pro-inflammatory to an anti-inflammatory mode.Taken together, this study presents first evidence demonstrating that diabetic wounds suffer from dysfunctional macrophage efferocytosis resulting in increased apoptotic cell burden at the wound site. This burden, in turn, prolongs the inflammatory phase and complicates wound healing.

  20. Postpartum reversibility of impaired incretin effect in gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Kosinski, M; Knop, F K; Vedtofte, L

    2013-01-01

    The potential reversibility of a reduced incretin effect is unclear. We investigated the incretin effect during third trimester and 3 to 4months postpartum in women with and without gestational diabetes mellitus (GDM). Ten women with GDM (plasma glucose (PG) concentration at 120min after 75g...... with GDM, the incretin effect increased significantly postpartum (31±6 vs. 56±6%, p=0.02), whereas the increment in women with NGT was insignificant (35±12 vs. 56±9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal (GIGD=100%×(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic...

  1. Study on cognitive impairment in diabetic rats by different behavioral experiments

    Science.gov (United States)

    Yu-bin, Ji; Zeng-yi, Li; Guo-song, Xin; Chi, Wei; Hong-jian, Zhu

    2017-12-01

    Object recognition test and Y maze test are widely used in learning and memory behavior evaluation techniques and methods. It was found that in the new object recognition experiment, the diabetic rats did more slowly than the normal rats in the discrimination of the old and new objects, and the learning and memory of the rats in the diabetic rats were injured. And the ratio of retention time and the number of errors in the Y maze test was much higher than that in the blank control group. These two methods can reflect the cognitive impairment in diabetic rats.

  2. Diabetic Hyperglycemia: Link to Impaired Glucose Transport in Pancreatic β Cells

    Science.gov (United States)

    Unger, Roger H.

    1991-03-01

    Glucose uptake into pancreatic β cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia. In both autoimmune and nonautoimmune diabetes, this glucose transport is reduced as a consequence of down-regulation of the normal β-cell transporter. In autoimmune diabetes, circulating immunoglobulins can further impair this glucose transport by inhibiting functionally intact transporters. Insights into mechanisms of the unresponsiveness of β cells to hyperglycemia may improve the management and prevention of diabetes.

  3. A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

    Science.gov (United States)

    Sonoda, Nao; Morimoto, Akiko; Tatsumi, Yukako; Asayama, Kei; Ohkubo, Takayoshi; Izawa, Satoshi; Ohno, Yuko

    2018-05-01

    To assess the impact of diabetes on restrictive and obstructive lung function impairment. This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) impairment or until March 2014. During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment. Copyright © 2017. Published by Elsevier Inc.

  4. Impaired response of mature adipocytes of diabetic mice to hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seok Jong, E-mail: seok-hong@northwestern.edu; Jin, Da P.; Buck, Donald W.; Galiano, Robert D.; Mustoe, Thomas A., E-mail: tmustoe@nmh.org

    2011-10-01

    Adipose tissue contains various cells such as infiltrated monocytes/macrophages, endothelial cells, preadipocytes, and adipocytes. Adipocytes have an endocrine function by secreting adipokines such as interleukin (IL)-6, tumor necrosis factor (TNF)-{alpha}, leptin, and adiponectin. Dysregulation of adipokines in adipose tissues leads to a chronic low-grade inflammation which could result in atherosclerosis, hypertension, and type 2 diabetes. A sustained inflammatory state, which is characterized by prolonged persistence of macrophages and neutrophils, is found in diabetic wounds. In addition, subcutaneous adipocytes are enormously increased in amount clinically in type 2 diabetes. However, the function of subcutaneous adipocytes, which play an important role in injured tissue subjected to hypoxia, has not been well characterized in vitro due to the difficulty of maintaining mature adipocytes in culture using conventional methods because of their buoyancy. In this study, we established a novel in vitro culture method of mature adipocytes by enclosing them in a hyaluronan (HA) based hydrogel to study their role in response to stress such as hypoxia. BrdU labeling and Ki67 immunostaining experiments showed that hydrogel enclosed mature adipocytes proliferate in vitro. Both mRNA and protein expression analyses for hypoxia regulated genes, such as vascular endothelial growth factor (VEGF) and heme oxygenase 1 (HO1), showed that mature adipocytes of wild type mice respond to hypoxia. In contrast, mature adipocytes of diabetic db/db and TallyHo mice did not efficiently respond to hypoxia. Our studies suggest that mature adipocytes are functionally active cells, and their abnormal function to hypoxia can be one of underlining mechanisms in type 2 diabetes.

  5. Hydro-alcoholic Extract of Commiphora mukul Gum Resin May Improve Cognitive Impairments in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Salehi

    2015-02-01

    Full Text Available Background Diabetes causes cognitive impairment. Medicinal plants due to different mechanisms, such as antioxidant activities may improve diabetes and relieve its symptoms. Commiphora mukul (Burseraceae has a significant antioxidant activity. Objectives This study aimed to examine the effect of hydro- alcoholic extract of C. mukul on passive-avoidance learning and memory in streptozotocin (STZ induced diabetic male rats. Materials and Methods Thirty-two adult male Wistar rats were randomly allocated to four groups: normal, diabetic, normal + extract of C. mukul and diabetic + extract of C. mukul groups with free access to regular rat diet. Diabetes was induced in male rats by single interaperitoneal injection of 60 mg/kg STZ. After the confirmation of diabetes, 300 mg/kg C. mukul extract was orally administered to the extract-treated groups. Control groups received normal saline at the same time. Passive-avoidance memory was tested eight weeks after the STZ treatment, and blood glucose and body weight were measured in all groups at the beginning and end of the experiment. Results In the present study, diabetes decreased learning and memory. Although the administration of C. mukul extract did not affect the step-through latency (STLa and the number of trials of the diabetic groups during the first acquisition trial, a significant decrease was observed in STLr and also a significant increase in time spent in the dark compartment (TDC and number of crossing (NOC in the retention test (after 24 and 48 hours. Although no significant difference was observed in body weight of diabetic + extract of C. mukul (DE and diabetic control (DC groups, the plasma glucose of DE group was significantly lower in comparison to DC group. Conclusions Commiphora mukul extract can improve passive-avoidance learning and memory impairments in the STZ-induced diabetic rats. This improvement may be due to the antioxidant, acetylcholinesterase inhibitory activity, anti

  6. Impaired Biomechanical Properties of Diabetic Skin Implications in Pathogenesis of Diabetic Wound Complications

    NARCIS (Netherlands)

    Bermudez, Dustin M.; Herdrich, Benjamin J.; Xu, Junwang; Lind, Robert; Beason, David P.; Mitchell, Marc E.; Soslowsky, Louis J.; Liechty, Kenneth W.

    Diabetic skin is known to have deficient wound healing properties, but little is known of its intrinsic biomeclhanical properties. We hypothesize that diabetic skin possesses inferior biomechanical properties at baseline, rendering it more prone to injury. Skin from diabetic and nondiabetic mice and

  7. Crocin Improved Learning and Memory Impairments in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2013-01-01

    Full Text Available Objective(s: Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP injection of streptozotocin (STZ, 45 mg/kg. Transfer latency (TL paradigm in elevated plus-maze (EPM was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC and malondialdehyde (MDA, blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1 and retention transfer latency (TL2, and MDA, decreased transfer latency shortening (TLs and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

  8. Skin Autofluorescence Based Decision Tree in Detection of Impaired Glucose Tolerance and Diabetes

    NARCIS (Netherlands)

    Smit, Andries J.; Smit, Jitske M.; Botterblom, Gijs J.; Mulder, Douwe

    2013-01-01

    Aim: Diabetes (DM) and impaired glucose tolerance (IGT) detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF) is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE) which are considered to be a carrier of glycometabolic memory. We

  9. Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial

    Directory of Open Access Journals (Sweden)

    Natália Chantal Magalhães da Silva

    2015-08-01

    Full Text Available AbstractObjective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus.Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21 and Control group (n = 24, received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05.Results: participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling.Conclusion: the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.

  10. An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

    Science.gov (United States)

    van der Lely, Heather K. J.; Payne, Elisabeth; McClelland, Alastair

    2011-01-01

    Background The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is “fragile”. Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no “gold-standard” to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test – a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI). Methods and Findings We tested three groups of children; two groups aged 3;6–6:6, a typically developing (n = 30) group, and a group diagnosed with SLI: (n = 11) (Young (Y)-SLI), and a further group aged 6;9–8;11 with SLI (Older (O)-SLI) (n = 10) who were above the test age norms. We employed a battery of language assessments including the GAPS test to assess the children's language abilities. For Y-SLI children, analyses revealed a sensitivity and specificity at the 5th and 10th percentile of 1.00 and 0.98, respectively, and for O-SLI children at the 10th and 15th percentile .83 and .90, respectively. Conclusions The findings reveal that the GAPS is highly accurate in identifying impaired vs. non-impaired children up to 6;8 years, and has moderate-to-high accuracy up to 9 years. The results indicate that GAPS is a realistic tool for the early identification of grammatical abilities and impairment in young children. A larger

  11. Pain and functional impairment as mediators of the link between medical symptoms and depression in type 2 diabetes.

    Science.gov (United States)

    Sacco, William P; Bykowski, Cathy A; Mayhew, Laura L

    2013-03-01

    Among people with diabetes, depression is more common and is associated with greater morbidity and mortality. A better understanding of mechanisms underlying the link between poor health and depression is needed. Pain and functional impairment may account for the effect of poor health on depression in diabetes. The purpose of the study was to examine whether pain and functional impairment mediate the association between diabetes-related medical symptoms and depression in type 2 diabetes. Adults diagnosed with type 2 diabetes (N = 77) completed the following measures: Patient Health Questionnaire (PHQ), Diabetes Symptom Checklist (DSC), and Medical Outcomes Study 12-item Short-Form Health Survey (SF-12). Body mass index (BMI) was computed using height and weight data from medical records. Mediation and linear regression analyses were conducted. Pain and functional impairment made significant, independent contributions to depression. Functional impairment mediated the link between diabetes-related medical symptoms and depression. Pain mediated the association between higher BMI and depression. Pain and functional impairment appear to play important, independent roles in depression in type 2 diabetes. Mediation analyses suggest the following: 1. diabetes-related medical problems increase functional impairment, which in turn leads to greater depression; and 2. the burden of carrying greater body mass (higher BMI) increases pain, which leads to increased depression.

  12. Diabetes Increases Cryoinjury Size with Associated Effects on Cx43 Gap Junction Function and Phosphorylation in the Mouse Heart.

    Science.gov (United States)

    Palatinus, Joseph A; Gourdie, Robert G

    2016-01-01

    Diabetic patients develop larger myocardial infarctions and have an increased risk of death following a heart attack. The poor response to myocardial injury in the diabetic heart is likely related to the many metabolic derangements from diabetes that create a poor substrate in general for wound healing, response to injury and infection. Studies in rodents have implicated a role for the gap junction protein connexin 43 (Cx43) in regulating the injury response in diabetic skin wounds. In this study, we sought to determine whether diabetes alters Cx43 molecular interactions or intracellular communication in the cryoinjured STZ type I diabetic mouse heart. We found that epicardial cryoinjury size is increased in diabetic mice and this increase is prevented by preinjury insulin administration. Consistent with these findings, we found that intercellular coupling via gap junctions is decreased after insulin administration in diabetic and nondiabetic mice. This decrease in coupling is associated with a concomitant increase in phosphorylation of Cx43 at serine 368, a residue known to decrease channel conductance. Taken together, our results suggest that insulin regulates both gap junction-mediated intercellular communication and injury propagation in the mouse heart.

  13. Factors that drive the gap in diabetes rates between Aboriginal and non-Aboriginal people in non-remote NSW.

    Science.gov (United States)

    Reeve, Rebecca; Church, Jody; Haas, Marion; Bradford, Wylie; Viney, Rosalie

    2014-10-01

    To identify factors underpinning the gap in diabetes rates between Aboriginal and non-Aboriginal people in non-remote NSW. This will indicate appropriate target areas for policy and for monitoring progress towards reducing the gap. Data from the 2004-05 National Health Survey and National Aboriginal and Torres Strait Islander Health Survey were used to estimate differences in self-reported diabetes rates and risk/prevention factors between Aboriginal and non-Aboriginal people in non-remote NSW. Logistic regression models were used to investigate the contribution of each factor to predicting the probability of diabetes. Risk factors for diabetes are more prevalent and diabetes rates 2.5 to 4 times higher in Aboriginal compared to non-Aboriginal adults in non-remote NSW. The odds of (known) diabetes for both groups are significantly higher for older people, those with low levels of education and those who are overweight or obese. In the Aboriginal sample, the odds of diabetes are significantly higher for people reporting forced removal of their relatives. Differences in BMI and education appear to be driving the diabetes gap, together with onset at younger ages in the Aboriginal population. Psychological distress, indicated by removal of relatives, may contribute to increased risk of diabetes in the Aboriginal population. The results imply that improved nutrition and exercise, capacity to access and act upon health care information and early intervention are required to reduce the diabetes gap. Current strategies appear to be appropriately aligned with the evidence; however, further research is required to determine whether implementation methods are effective. © 2014 Public Health Association of Australia.

  14. The relationship between C-type natriuretic peptide and cognitive impairment in older patients with Type 2 diabetes

    International Nuclear Information System (INIS)

    Li Xinling; Zhu Xiangyang; Huang Huaiyu; Jin Yan

    2011-01-01

    Objective: To investigate the relationship between C-type natriuretic peptide and cognitive impairment in older patients with type 2 diabetes, and to explore the pathogenesis of diabetic cognitive impairment. Methods: According to the Montreal Cognitive Assessment (MoCA) scores, 80 type 2 diabetic patients over the age of 60 years were divided into two groups, one group including 31 cases with cognitive impairment, the other 49 patients with non-cognitive impairment. And 80 normal participants were selected as the control group. Plasma level of C-type natriuretic peptide was measured by radio-immunity assay in all subjects. The changes and associations of the plasma C-type natriuretic peptide level among three groups was analyzed. Result: In the non-cognitive impairment group, plasma level of C-type natriuretic peptide was higher than that in the control group (P<0.01). But the plasma level of C-type natriuretic peptide in the cognitive impairment group was degraded, significantly deferent with those in the control group and the non-cognitive impairment group (P<0.01). MoCA scores of the cognitive impairment group positively correlated with plasma level of C-type natriuretic peptide (r=0.513, P<0.01). Conclusion: In the early period of type 2 diabetes,the secretion of C-type natriuretic peptide was increased. When diabetic cognitive impairment complicated,the secretion of C-type natriuretic peptide was decompensated. Then plasma level of C-type natriuretic peptide become low. The level of C-type natriuretic peptide closely correlated with diabetic cognitive impairment. It was suggested that diabetic angiopathies may act an important role in the pathogenesis of diabetic cognitive impairment. (authors)

  15. Neuropsychological Impairment in School-Aged Children Born to Mothers With Gestational Diabetes.

    Science.gov (United States)

    Bolaños, Lourdes; Matute, Esmeralda; Ramírez-Dueñas, María de Lourdes; Zarabozo, Daniel

    2015-10-01

    The aim of this study was to determine whether school-aged children born to mothers with gestational diabetes show delays in their neuropsychological development. Several key neuropsychological characteristics of 32 children aged 7 to 9 years born to mothers with gestational diabetes were examined by comparing their performance on cognitive tasks to that of 28 children aged 8 to 10 years whose mothers had glucose levels within normal limits during pregnancy. The gestational diabetes group showed low performance on graphic, spatial, and bimanual skills and a higher presence of soft neurologic signs. Lower scores for general intellectual level and the working memory index were also evident. Our results suggest that gestational diabetes is associated with mild cognitive impairment. © The Author(s) 2015.

  16. Resveratrol Improves Cognitive Impairment by Regulating Apoptosis and Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Zhiyan Tian

    2016-12-01

    Full Text Available Aims: To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ-induced diabetic rats and to explore the mechanisms of that phenomenon. Methods: Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15, Res group (normal Sprague Dawley rats treated with resveratrol, n = 15, diabetes mellitus group (DM group, n = 15 and DM + Res group (diabetic rats treat with resveratrol, n = 15. Streptozotocin (STZ was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor and BDNF (Brain Derived Neurotrophic Factor via western blotting analysis. Results: Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression. Conclusions: Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.

  17. Impaired Hedgehog signalling-induced endothelial dysfunction is sufficient to induce neuropathy: implication in diabetes.

    Science.gov (United States)

    Chapouly, Candice; Yao, Qinyu; Vandierdonck, Soizic; Larrieu-Lahargue, Frederic; Mariani, John N; Gadeau, Alain-Pierre; Renault, Marie-Ange

    2016-02-01

    Microangiopathy, i.e. endothelial dysfunction, has long been suggested to contribute to the development of diabetic neuropathy, although this has never been fully verified. In the present paper, we have identified the role of Hedgehog (Hh) signalling in endoneurial microvessel integrity and evaluated the impact of impaired Hh signalling in endothelial cells (ECs) on nerve function. By using Desert Hedgehog (Dhh)-deficient mice, we have revealed, that in the absence of Dhh, endoneurial capillaries are abnormally dense and permeable. Furthermore, Smoothened (Smo) conditional KO mice clarified that this increased vessel permeability is specifically due to impaired Hh signalling in ECs and is associated with a down-regulation of Claudin5 (Cldn5). Moreover, impairment of Hh signalling in ECs was sufficient to induce hypoalgesia and neuropathic pain. Finally in Lepr(db/db) type 2 diabetic mice, the loss of Dhh expression observed in the nerve was shown to be associated with increased endoneurial capillary permeability and decreased Cldn5 expression. Conversely, systemic administration of the Smo agonist SAG increased Cldn5 expression, decreased endoneurial capillary permeability, and restored thermal algesia to diabetic mice, demonstrating that loss of Dhh expression is crucial in the development of diabetic neuropathy. The present work demonstrates the critical role of Dhh in maintaining blood nerve barrier integrity and demonstrates for the first time that endothelial dysfunction is sufficient to induce neuropathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  18. Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial.

    Science.gov (United States)

    da Silva, Natália Chantal Magalhães; Chaves, Érika de Cássia Lopes; de Carvalho, Emilia Campos; Carvalho, Leonardo César; Iunes, Denise Hollanda

    2015-01-01

    to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus. this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.

  19. Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial 1

    Science.gov (United States)

    da Silva, Natália Chantal Magalhães; Chaves, Érika de Cássia Lopes; de Carvalho, Emilia Campos; Carvalho, Leonardo César; Iunes, Denise Hollanda

    2015-01-01

    Abstract Objective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus. Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz. PMID:26444161

  20. Impaired atrial electromechanical function and atrial fibrillation promotion in alloxan-induced diabetic rabbits.

    Science.gov (United States)

    Fu, Huaying; Liu, Changle; Li, Jian; Zhou, Changyu; Cheng, Lijun; Liu, Tong; Li, Guangping

    2013-01-01

    Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms are still not clearly elucidated. The aim of this study was to evaluate the atrial electromechanical function, atrial electrophysiological changes and AF inducibility in alloxan-induced diabetic rabbits. In 8 alloxan-induced diabetic rabbits and 8 controls, we evaluated atrial electromechanical function by tissue Doppler imaging. Isolated Langendorff-perfused rabbit hearts were prepared to measure atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF. Atrial interstitial fibrosis was evaluated by Sirius-Red staining. Compared with controls, left atrial lateral wall Pa'-start interval (Pastart) and right atrial wall Pastart were increased in diabetic rabbits. AERPD was increased and IACT was prolonged in diabetic rabbits. Inducibility of AF in diabetic group was significant higher than controls (6/8 vs. 1/8, p TEMA); left atrial lateral wall Papeak and TEMA, left atrial posterior wall TEMA, and IACT were correlated with atrial areas of fibrosis. Atrial electromechanical function is impaired in diabetic rabbits, and is associated with atrial fibrosis and interatrial electrical conduction delay.

  1. Acute glycaemic load breakfast manipulations do not attenuate cognitive impairments in adults with type 2 diabetes.

    Science.gov (United States)

    Lamport, Daniel Joseph; Dye, Louise; Mansfield, Michael W; Lawton, Clare L

    2013-04-01

    Research on young healthy samples suggests that low glycaemic load foods can confer benefits for cognitive performance. The aim was to examine the effects of type 2 diabetes on cognitive function, and to investigate whether consumption of low glycaemic load breakfasts affects cognitive function in adults with type 2 diabetes. Memory, psychomotor skill and executive function were examined at two morning test sessions in 24 adults with type 2 diabetes and 10 adults with normal glucose tolerance (NGT) aged 45-77 years without dementia after water, low, and high glycaemic load breakfasts were consumed in accordance with a crossover, counterbalanced design. The type 2 diabetes and NGT groups were matched for education, depression, and IQ. Type 2 diabetes was associated with impairments in verbal memory, spatial memory, psychomotor skill, and executive function compared to adults with NGT. Consumption of the three breakfast conditions did not impact on cognitive performance in the type 2 diabetes or NGT participants. Abnormalities in glucose tolerance such as type 2 diabetes can have demonstrable negative effects on a range of cognitive functions. However, there was no evidence that low GL breakfasts administered acutely could confer benefits for cognitive function (ClincalTrials.gov identifier, NCT01047813). Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  2. Progression to impaired glucose regulation and diabetes in the population-based Inter99 study

    DEFF Research Database (Denmark)

    Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine

    2009-01-01

    Objective: To estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population-based Inter99 study and in a high-risk subpopulation, separately. Research Design and Methods: From a population-based primary...... glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies....... prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity...... estimated directly from baseline to 5-year follow-up for all the participants, and from baseline through 1- and 3-, to 5-year follow-up for the high-risk individuals, separately. Results: In the combined low- and high-risk group, 2.1 per 100 person-years progressed from normal glucose tolerance to impaired...

  3. Hypoglycemia Is Independently Associated with Multidimensional Impairment in Elderly Diabetic Patients

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    A. Pilotto

    2014-01-01

    Full Text Available Aim. To identify the characteristics associated with multidimensional impairment, evaluated through the Multidimensional Prognostic Index (MPI, a validated predictive tool for mortality derived from a standardized Comprehensive Geriatric Assessment (CGA, in a cohort of elderly diabetic patients treated with oral hypoglycemic drugs. Methods and Results. The study population consisted of 1342 diabetic patients consecutively enrolled in 57 diabetes centers distributed throughout Italy, within the Metabolic Study. Inclusion criteria were diagnosis of type 2 diabetes mellitus (DM, 65 years old or over, and treatment with oral antidiabetic medications. Data concerning DM duration, medications for DM taken during the 3-month period before inclusion in the study, number of hypoglycemic events, and complications of DM were collected. Multidimensional impairment was assessed using the MPI evaluating functional, cognitive, and nutritional status; risk of pressure sores; comorbidity; number of drugs taken; and cohabitation status. The mean age of participants was 73.3 ± 5.5 years, and the mean MPI score was 0.22 ± 0.13. Multivariate analysis showed that advanced age, female gender, hypoglycemic events, and hospitalization for glycemic decompensation were independently associated with a worse MPI score. Conclusion. Stratification of elderly diabetic patients using the MPI might help to identify those patients at highest risk who need better-tailored treatment.

  4. Interactive effects of diabetes and impaired kidney function on cognitive performance in old age: a population-based study.

    Science.gov (United States)

    Yin, Zhaoxue; Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Song, Aiqin; Feng, Lei; Qiu, Chengxuan

    2016-01-12

    The interactive effect between diabetes and impaired kidney function on cognitive impairment in older adults has not yet been reported. The aim of this study was to investigate the association of diabetes and impaired kidney function with cognitive impairment among Chinese older people living in a rural area. This cross-sectional study included 1,358 participants (age ≥60 years; 60.5% women) in the population-based Confucius Hometown Aging Project in Shandong, China. Data on demographics, lifestyle factors, health history, use of medications, global cognitive function, and kidney function were collected through structured interviews, clinical examinations, and blood tests. We defined diabetes as a fasting plasma glucose level ≥7.0 mmol/l or use of hypoglycemic agents, impaired kidney function as glomerular filtration rate estimated from cystatin C (eGFRcys) Cognitive impairment was defined using the education-based cut-off scores of Mini-Mental State Examination (MMSE). Data were analyzed using multiple general linear and logistic regression models. Cognitive impairment was defined in 197 (14.5%) persons. The multi-adjusted β coefficient of MMSE score associated with diabetes was -0.06 (95% confidence interval [CI], -0.16, 0.03); the corresponding figures associated with eGFRcys function showed an interactive effect on cognitive impairment ( interaction = 0.02). Compared with individuals having neither diabetes nor impaired kidney function, those with both conditions had a multi-adjusted odds ratio of 4.23 (95% CI, 2.10-8.49) for cognitive impairment. The relative excess risk due to interaction was 2.74. This study suggests that concurrent presence of diabetes and impaired kidney function is associated with a substantial likelihood for cognitive impairment in older adults.

  5. Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF rats

    Directory of Open Access Journals (Sweden)

    Olsen Kristine Boisen

    2013-01-01

    Full Text Available Abstract Background Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV, which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ induced type 1 diabetes. Whether CV is also disturbed in models of type 2 diabetes is currently unknown. Methods We used Zucker Diabetic Fatty (ZDF rats, as a model of type 2 diabetes, and their lean controls Zucker Diabetic Lean (ZDL rats to investigate CV and its response to the anti-arrhythmic peptide analogue AAP10. Gap junction remodeling was examined by immunofluorescence and western blotting. Cardiac histomorphometry was examined by Masson`s Trichrome staining and intracellular lipid accumulation was analyzed by Bodipy staining. Results CV was significantly slower in ZDF rats (56±1.9 cm/s compared to non-diabetic controls (ZDL, 66±1.6 cm/s, but AAP10 did not affect CV in either group. The total amount of Connexin43 (C×43 was identical between ZDF and ZDL rats, but the amount of lateralized C×43 was significantly increased in ZDF rats (42±12 % compared to ZDL rats (30±8%, p Conclusion CV is reduced in type 2 diabetic ZDF rats. The CV disturbance may be partly explained by increased lateralization of C×43, but other factors are likely also involved. Our data indicates that lipotoxicity potentially may play a role in development of conduction disturbances and arrhythmias in type 2 diabetes.

  6. Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

    Science.gov (United States)

    Le, Jimmy T; Hutfless, Susan; Li, Tianjing; Bressler, Neil M; Heyward, James; Bittner, Ava K; Glassman, Adam; Dickersin, Kay

    2017-01-01

    Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME). Cross-sectional study. Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators. We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions. Ranking of importance of each clinical question. Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review. A limited response rate among

  7. Flos Puerariae Extract Ameliorates Cognitive Impairment in Streptozotocin-Induced Diabetic Mice

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    Zhong-he Liu

    2015-01-01

    Full Text Available Objective. The effects of Flos Puerariae extract (FPE on cognitive impairment associated with diabetes were assessed in C57BL/6J mice. Methods. Experimental diabetic mice model was induced by one injection of 50 mg/kg streptozotocin (STZ for 5 days consecutively. FPE was orally administrated at the dosages of 50, 100, or 200 mg/kg/day, respectively. The learning and memory ability was assessed by Morris water maze test. Body weight, blood glucose, free fatty acid (FFA and total cholesterol (TCH in serum, malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, and acetylcholinesterase (AChE activities in cerebral cortex and hippocampus were also measured. Results. Oral administration of FPE significantly improved cognitive deficits in STZ-induced diabetic mice. FPE treatment also maintained body weight and ameliorated hyperglycemia and dyslipidemia in diabetic mice. Additionally, decreased MDA level, enhanced CAT, and GSH-Px activities in cerebral cortex or hippocampus, as well as alleviated AChE activity in cerebral cortex, were found in diabetic mice supplemented with FPE. Conclusion. This study suggests that FPE ameliorates memory deficits in experimental diabetic mice, at least partly through the normalization of metabolic abnormalities, ameliorated oxidative stress, and AChE activity in brain.

  8. Prevalence of diabetes mellitus and impaired glucose tolerance in a New Zealand multiracial workforce.

    Science.gov (United States)

    Scragg, R; Baker, J; Metcalf, P; Dryson, E

    1991-09-25

    A cross sectional survey was carried out among a multiracial workforce of 5677 staff aged 40 to 64 years at worksites in Auckland and Tokoroa to determine the prevalence of diabetes mellitus and impaired glucose tolerance (IGT). The prevalences of diabetes mellitus and IGT were both similar for men and women, but increased with age. The relative risks for diabetes mellitus and for IGT were both inversely associated with gross annual household income, independent of age and ethnicity, being 1.61 (95% Cl = 1.10, 2.37) and 1.80 (95% Cl = 1.21, 2.67) respectively, in the lowest income group (less than $30,000) compared with the highest (greater than $40,000). Compared with Europeans, the relative risk of diabetes mellitus was significantly increased among Maori (3.63; 95% Cl = 2.48, 5.32), Pacific Islanders (2.34; 95% Cl = 1.50, 3.66) and Asians (5.97; 95% Cl = 2.61, 13.65), after controlling for age, income and body mass index. The increased prevalence of diabetes mellitus among Maori and Pacific Islanders, but not in Asians, could be partly attributed to their increased levels of obesity compared with Europeans. However, other factors, in addition to obesity, explain the increased diabetes prevalence in nonEuropean groups.

  9. Prevalence of Diabetes Mellitus and Impaired Fasting Blood Glucose in Patients with Lichen Planus

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    Shadi Peyghambari

    2012-02-01

    Full Text Available Background: The relationship between Lichen Planus (LP and diabetes was studied previously, but the re-sults were in conflict. The aim of this study was to find the prevalence of diabetes mellitus (DM in patients with LP among Iranian patients. Methods: In this study, 80 patients with LP were enrolled. They referred to dermatology clinic of our hospital during one year. A self-designed checklist for the study included duration of the disease, the pattern of the dis-tribution of lichenoid lesions and fasting blood sugar (FBS. Results: From 80 patients with LP, 16 (20% had diabetes. Also, 14 patients (17.5% had impaired fasting glucose. The mean age of diabetic patients was significantly higher than non-diabetic group (p=0.039. In addi-tion, the duration of LP in patients with DM was significantly higher than non-diabetic patients (p=0.024. Conclusion: In our study, we saw a high prevalence of DM among patients with LP. Comparing our findings with the overall prevalence of DM in Iran, there was a significant difference between the prevalence of DM among patients with LP and the overall prevalence (p=0.001. Regarding our findings screening for FBS in pa-tients with LP is required in Iran.

  10. Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

    Science.gov (United States)

    Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

    2016-09-01

    Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

  11. Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model

    Directory of Open Access Journals (Sweden)

    Dun C

    2016-07-01

    Full Text Available Changping Dun,1 Junqian Liu,1 Fucheng Qiu,1 Xueda Wu,2 Yakun Wang,3 Yongyan Zhao,4 Ping Gu1 1Department of Neurology, the First Hospital of Hebei Medical University, 2Department of Cardiac Surgery, the Second Hospital of Hebei Medical University, 3Department of Endocrinology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 4Department of Nursing, Maternal and Child Health Hospital of Tangshan City, Tangshan, People’s Republic of China Objective: Astragalus polysaccharides (APS are active constituents of Astragalus membranaceus. In this study, we aimed to investigate the effects of APS on memory impairment in a diabetic rat model and their mechanisms. Methods: A diabetic model was established in 50 male Wistar rats with streptozotocin intraperitoneal injection. A blood glucose level higher than 16.7 mmol/L obtained 72 hours after the injection was regarded as a successful diabetic model. The modeled rats were divided into model group, high, medium, and low doses of APS, and piracetam groups (positive control. A group of ten rats without streptozotocin-induced diabetes were used as a normal control. After respective consecutive 8-week treatments, the levels of blood fasting plasma glucose, insulin, hemoglobin A1c, memory performance, hippocampal malondialdehyde, and superoxide dismutase were determined. Results: After the 8-week APS treatment, serum fasting plasma glucose, hemoglobin A1c, and insulin levels were decreased compared with those of the model group (P<0.05. Importantly, memory impairment in the diabetic model was reversed by APS treatments. In addition, hippocampal malondialdehyde concentration was lowered, whereas that of superoxide dismutase was higher after APS treatments. Conclusion: APS are important active components responsible for memory improvement in rats with streptozotocin-induced diabetes. The potential mechanism of action is associated with the effects of APS on glucose and lipid metabolism, and

  12. Prevalence of depression in individuals with impaired glucose metabolism or undiagnosed diabetes

    DEFF Research Database (Denmark)

    Nouwen, Arie; Nefs, Giesje; Caramlau, Isabela

    2011-01-01

    diagnosed type 2 diabetes (PDD) has not been the subject of a systematic review/meta-analysis. This study examined the prevalence of depression in IGM and UDD subjects relative to each other and to NGM and PDD subjects by reviewing the literature and conducting a meta-analysis of studies on this topic......OBJECTIVE: Meta-analyses have shown that the risk for depression is elevated in type 2 diabetes. Whether this risk in individuals with impaired glucose metabolism (IGM) or undiagnosed diabetes (UDD) is elevated relative to normal glucose metabolism (NGM) or decreased relative to previously....... RESEARCH DESIGN AND METHODS: EMBASE and MEDLINE databases were searched for articles published up to May 2010. All studies that compared the prevalence of depression in subjects with IGM and UDD were included. Odds ratios (ORs) were calculated using fixed and random-effects models. RESULTS: The meta-analysis...

  13. Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Heine, R. J.

    2008-01-01

    .28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non-significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms...... reduced the strength of these associations. CONCLUSIONS: Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could......OBJECTIVE: To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). RESEARCH DESIGN AND METHODS: Cross-sectional data from a population-based cohort study conducted...

  14. Gap analysis : bus signage guidelines for persons with visual impairments : electronic signs

    Science.gov (United States)

    2001-09-01

    This report focuses on the adequacy of Americans with Disabilities Act (ADA) destination signage guidelines for visual technologies used to improve the dissemination of public transit information to the visually impaired. Specifically, this document ...

  15. Impaired Fasting Glucose in Omani Adults with no Family History of Type 2 Diabetes

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    Sawsan Al-Sinani

    2014-05-01

    Full Text Available Objectives: The aim of this study was to estimate the prevalence of impaired fasting glucose (IFG among Omani adults with no family history (FH of diabetes and to investigate the factors behind the risk of developing type 2 diabetes (T2D, while excluding a FH of diabetes. Methods: A total of 1,182 Omani adults, aged ≥40 years, visited the Family Medicine & Community Health Clinic at Sultan Qaboos University Hospital, Oman, on days other than the Diabetes Clinic days, from July 2010 to July 2011. The subjects were interviewed and asked if they had T2D or a FH of T2D. Results: Only 191 (16% reported no personal history of T2D or FH of the disease. Of these, anthropometric and biochemical data was complete in 159 subjects. Of these a total of 42 (26% had IFG according to the American Diabetes Association criteria. Body mass index, fasting insulin, haemoglobin A1C and blood pressure (BP, were significantly higher among individuals with IFG (P <0.01, P <0.05, P <0.01 and P <0.01, respectively. In addition, fasting insulin, BP and serum lipid profile were correlated with obesity indices (P <0.05. Obesity indices were strongly associated with the risk of IFG among Omanis, with waist circumference being the strongest predictor. Conclusion: Despite claiming no FH of diabetes, a large number of Omani adults in this study had a high risk of developing diabetes. This is possibly due to environmental factors and endogamy. The high prevalence of obesity combined with genetically susceptible individuals is a warning that diabetes could be a future epidemic in Oman.

  16. Multimodal MRI for early diabetic mild cognitive impairment: study protocol of a prospective diagnostic trial

    International Nuclear Information System (INIS)

    Yu, Ying; Sun, Qian; Yan, Lin-Feng; Hu, Yu-Chuan; Nan, Hai-Yan; Yang, Yang; Liu, Zhi-Cheng; Wang, Wen; Cui, Guang-Bin

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is a risk factor for dementia. Mild cognitive impairment (MCI), an intermediary state between normal cognition and dementia, often occurs during the prodromal diabetic stage, making early diagnosis and intervention of MCI very important. Latest neuroimaging techniques revealed some underlying microstructure alterations for diabetic MCI, from certain aspects. But there still lacks an integrated multimodal MRI system to detect early neuroimaging changes in diabetic MCI patients. Thus, we intended to conduct a diagnostic trial using multimodal MRI techniques to detect early diabetic MCI that is determined by the Montreal Cognitive Assessment (MoCA). In this study, healthy controls, prodromal diabetes and diabetes subjects (53 subjects/group) aged 40-60 years will be recruited from the physical examination center of Tangdu Hospital. The neuroimaging and psychometric measurements will be repeated at a 0.5 year-interval for 2.5 years’ follow-up. The primary outcome measures are 1) Microstructural and functional alterations revealed with multimodal MRI scans including structure magnetic resonance imaging (sMRI), resting state functional magnetic resonance imaging (rs-fMRI), diffusion kurtosis imaging (DKI), and three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL); 2) Cognition evaluation with MoCA. The second outcome measures are obesity, metabolic characteristics, lifestyle and quality of life. The study will provide evidence for the potential use of multimodal MRI techniques with psychometric evaluation in diagnosing MCI at prodromal diabetic stage so as to help decision making in early intervention and improve the prognosis of T2DM. This study has been registered to ClinicalTrials.gov (NCT02420470) on April 2, 2015 and published on July 29, 2015

  17. Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

    Science.gov (United States)

    Wang, Pei; Yang, Xi; Zhang, Zheng; Song, Jie; Guan, Yun-Feng; Zou, Da-Jin; Miao, Chao-Yu

    2016-06-01

    The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood

  18. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia.

    Science.gov (United States)

    Lerman, Oren Z; Galiano, Robert D; Armour, Mary; Levine, Jamie P; Gurtner, Geoffrey C

    2003-01-01

    Although it is known that systemic diseases such as diabetes result in impaired wound healing, the mechanism for this impairment is not understood. Because fibroblasts are essential for wound repair, we compared the in vitro behavior of fibroblasts cultured from diabetic, leptin receptor-deficient (db/db) mice with wild-type fibroblasts from mice of the same genetic background in processes important during tissue repair. Adult diabetic mouse fibroblast migration exhibited a 75% reduction in migration compared to normal fibroblasts (P under basal or hypoxic conditions, confirming that the results from db/db fibroblasts in mature mice resulted from the diabetic state and were not because of alterations in the leptin-leptin receptor axis. Markers of cellular viability including proliferation and senescence were not significantly different between diabetic and wild-type fibroblasts. We conclude that, in vitro, diabetic fibroblasts show selective impairments in discrete cellular processes critical for tissue repair including cellular migration, VEGF production, and the response to hypoxia. The VEGF abnormalities developed concurrently with the onset of hyperglycemia and were not seen in normoglycemic, leptin receptor-deficient db/db mice. These observations support a role for fibroblast dysfunction in the impaired wound healing observed in human diabetics, and also suggest a mechanism for the poor clinical outcomes that occur after ischemic injury in diabetic patients.

  19. Early myocardial impairment in type 1 diabetes patients without known heart disease assessed with tissue Doppler echocardiography

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Søgaard, Peter; Andersen, Henrik Ullits

    2016-01-01

    PURPOSE: Cardiovascular disease is the most common cause of mortality in type 1 diabetes; patients with albuminuria are at greatest risk. We investigated myocardial function and premature myocardial impairment in type 1 diabetes patients with and without albuminuria compared to controls. METHODS:...

  20. Risk factors for development of impaired renal function in Type 2 diabetes mellitus patients in primary care.

    NARCIS (Netherlands)

    Naushahi, M.J.; Grauw, W.J.C. de; Avery, A.J.; Gerwen, W.H.E.M. van; Lisdonk, E.H. van de; Weel, C. van

    2004-01-01

    AIMS: To evaluate risk factors for the development of an impaired renal function, defined as a glomerular filtration rate (GFR) by Cockcroft-Gault formula < 50.5 ml/min, in primary care patients with Type 2 diabetes mellitus. METHODS: A case-control study of Type 2 diabetes mellitus patients with

  1. Prevalence and associated factors of diabetes and impaired fasting glucose in Chinese hypertensive adults aged 45 to 75 years.

    Directory of Open Access Journals (Sweden)

    Xianhui Qin

    Full Text Available This study examined the prevalence of impaired fasting glucose (IFG and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45-75 years.A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG ≥ 7.0 mmol/l] and IFG (6.1-6.9 mmol/l were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes.The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥ 25 kg/m(2, abdominal obesity (waist circumference ≥ 90 cm for men and ≥ 80 cm for women, non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal were important independent associated factors for IFG.In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation, and

  2. Adipokine pattern in subjects with impaired fasting glucose and impaired glucose tolerance in comparison to normal glucose tolerance and diabetes.

    Directory of Open Access Journals (Sweden)

    Anke Tönjes

    Full Text Available AIM: Altered adipokine serum concentrations early reflect impaired adipose tissue function in obese patients with type 2 diabetes (T2D. It is not entirely clear whether these adipokine alterations are already present in prediabetic states and so far there is no comprehensive adipokine panel available. Therefore, the aim of this study was to assess distinct adipokine profiles in patients with normal glucose tolerance (NGT, impaired fasting glucose (IFG, impaired glucose tolerance (IGT or T2D. METHODS: Based on 75 g oral glucose tolerance tests, 124 individuals were divided into groups of IFG (n = 35, IGT (n = 45, or NGT (n = 43. Furthermore, 56 subjects with T2D were included. Serum concentrations of adiponectin, chemerin, fetuin-A, leptin, interleukin (IL-6, retinol-binding protein 4 (RBP4, monocyte chemoattractant protein (MCP-1, vaspin, progranulin, and soluble leptin receptor (sOBR were measured by ELISAs. RESULTS: Chemerin, progranulin, fetuin-A, and RBP4, IL-6, adiponectin and leptin serum concentrations were differentially regulated among the four investigated groups but only circulating chemerin was significantly different in patients with IGT compared to those with IFG. Compared to T2D the IFG subjects had higher serum chemerin, progranulin, fetuin-A and RBP4 levels which was not detectable in the comparison of the T2D and IGT group. CONCLUSION: Alterations in adipokine serum concentrations are already detectable in prediabetic states, mainly for chemerin, and may reflect adipose tissue dysfunction as an early pathogenetic event in T2D development. In addition, distinct adipokine serum patterns in individuals with IFG and IGT suggest a specific role of adipose tissue in the pathogenesis of these prediabetic states.

  3. PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

    Science.gov (United States)

    Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

    2014-10-01

    In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands. © 2014 Society for Endocrinology.

  4. Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats

    Science.gov (United States)

    Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

    2015-01-01

    The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals. PMID:26197932

  5. Impaired glucose homeostasis in non-diabetic Greek hypertensives with diabetes family history. Effect of the obesity status.

    Science.gov (United States)

    Vyssoulis, Gregory P; Liakos, Charalampos I; Karpanou, Eva A; Triantafyllou, Athanasios I; Michaelides, Andreas P; Tzamou, Vanessa E; Markou, Maria I; Stefanadis, Christodoulos I

    2013-01-01

    Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 μU/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P history was significant (P history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups. Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

  6. Frequency of impaired oral glucose tolerance test in high risk pregnancies for gestational diabetes mellitus

    International Nuclear Information System (INIS)

    Naheed, F.; Narijo, S.; Kammeruddin, K.

    2008-01-01

    To determine the frequency of impaired oral glucose tolerance test in high risk pregnancies for Gestational Diabetes Mellitus (GDM). A total of 50 high risk pregnancies for gestational diabetes mellitus were selected through outpatient department of obstetrics. Data was collected according to certain obstetric and non-obstetric risk factors for GDM as inclusion criteria through a designed proforma i.e. family history of diabetes, macrosomia (i.e, wt > 3.5 kg), abortions, grand multiparity, a sudden increase in weight (>1 kg/wk) during pregnancy, age > 35 years, early neonatal deaths/sudden IUDS, polyhydramnios, urogenital infections (vulvo-vaginal candidiasis and UTI), previous history of GDM, congenital abnormalities (with or without polyhydramnios) and multiple pregnancy. Oral glucose tolerance test was performed and analyzed according to American Diabetic Association criteria, 2004. The most frequent risk factors were family history of diabetes mellitus in 1st degree relative and large for dates babies in 18 patients. Similarly, high risk factors such as history of abortions and grand multiparity were present in 16 and 14 pregnant women respectively. Least common factors, which contributed for GDM, were polyhydramnios in 4 cases and perinatal mortality (due to congenital anomalies of foetus, intrauterine deaths or neonatal deaths) seen only in 5 cases. Overall impaired oral glucose tolerance test was found in 24%. Most patients had one (17%) or two risk factors commonly (23%). Only 2% had shown five or more risk factors. Oral glucose tolerance test is a useful diagnostic tool to detect GDM in high risk pregnancies, depending upon the high frequency of number of risk factors in each individual. (author)

  7. Impaired TCA cycle flux in mitochondria in skeletal muscle from type 2 diabetic subjects: marker or maker of the diabetic phenotype?

    Science.gov (United States)

    Gaster, Michael; Nehlin, Jan O; Minet, Ariane D

    2012-07-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. Recent research has shown that diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux. A reduced TCA cycle flux has also been shown both in insulin resistant offspring of T2D patients and exercising T2D patients in vivo. This review will discuss the latest advances in the understanding of the molecular mechanisms regulating the TCA cycle with focus on possible underlying mechanism which could explain the impaired TCA flux in insulin resistant human skeletal muscle in type 2 diabetes. A reduced TCA is both a marker and a maker of the diabetic phenotype.

  8. Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice

    Science.gov (United States)

    Long, Y. S.; Zheng, S.; Kralik, P. M.; Benz, F. W.

    2016-01-01

    The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis. PMID:27822483

  9. Potential effects of current drug therapies on cognitive impairment in patients with type 2 diabetes.

    Science.gov (United States)

    Palleria, Caterina; Leporini, Christian; Maida, Francesca; Succurro, Elena; De Sarro, Giovambattista; Arturi, Franco; Russo, Emilio

    2016-07-01

    Type 2 diabetes mellitus is a complex metabolic disease that can cause serious damage to various organs. Among the best-known complications, an important role is played by cognitive impairment. Impairment of cognitive functioning has been reported both in type 1 and 2 diabetes mellitus. While this comorbidity has long been known, no major advances have been achieved in clinical research; it is clear that appropriate control of blood glucose levels represents the best current (although unsatisfactory) approach in the prevention of cognitive impairment. We have focused our attention on the possible effect on the brain of antidiabetic drugs, despite their effects on blood glucose levels, giving a brief rationale on the mechanisms (e.g. GLP-1, BDNF, ghrelin) that might be involved. Indeed, GLP-1 agonists are currently clinically studied in other neurodegenerative diseases (i.e. Parkinson's and Alzheimer's disease); furthermore, also other antidiabetic drugs have proven efficacy in preclinical studies. Overall, promising results are already available and finding new intervention strategies represents a current need in this field of research. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Ethnic variation in the prevalence of visual impairment in people attending diabetic retinopathy screening in the United Kingdom (DRIVE UK).

    Science.gov (United States)

    Sivaprasad, Sobha; Gupta, Bhaskar; Gulliford, Martin C; Dodhia, Hiten; Mann, Samantha; Nagi, Dinesh; Evans, Jennifer

    2012-01-01

    To provide estimates of visual impairment in people with diabetes attending screening in a multi-ethnic population in England (United Kingdom). The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK) Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London) or August 2009 (West Yorkshire) were included in the study. Data on age, gender, ethnic group, visual acuity and diabetic retinopathy were collected. Ethnic group was defined according to the 2011 census classification. The two main ethnic minority groups represented here are Blacks ("Black/African/Caribbean/Black British") and South Asians ("Asians originating from the Indian subcontinent"). We examined the prevalence of visual impairment in the better eye using three cut-off points (a) loss of vision sufficient for driving (approximately ethnic groups to the age-structure of the white population. Data on visual acuity and were available on 50,331 individuals 3.4% of people diagnosed with diabetes and attending screening were visually impaired (95% confidence intervals (CI) 3.2% to 3.5%) and 0.39% severely visually impaired (0.33% to 0.44%). Blacks and South Asians had a higher prevalence of visual impairment (directly age standardised prevalence 4.6%, 95% CI 4.0% to 5.1% and 6.9%, 95% CI 5.8% to 8.0% respectively) compared to white people (3.3%, 95% CI 3.1% to 3.5%). Visual loss was also more prevalent with increasing age, type 1 diabetes and in people living in Yorkshire. Visual impairment remains an important public health problem in people with diabetes, and is more prevalent in the minority ethnic groups in the UK.

  11. Skin autofluorescence based decision tree in detection of impaired glucose tolerance and diabetes.

    Directory of Open Access Journals (Sweden)

    Andries J Smit

    Full Text Available Diabetes (DM and impaired glucose tolerance (IGT detection are conventionally based on glycemic criteria. Skin autofluorescence (SAF is a noninvasive proxy of tissue accumulation of advanced glycation endproducts (AGE which are considered to be a carrier of glycometabolic memory. We compared SAF and a SAF-based decision tree (SAF-DM with fasting plasma glucose (FPG and HbA1c, and additionally with the Finnish Diabetes Risk Score (FINDRISC questionnaire±FPG for detection of oral glucose tolerance test (OGTT- or HbA1c-defined IGT and diabetes in intermediate risk persons.Participants had ≥1 metabolic syndrome criteria. They underwent an OGTT, HbA1c, SAF and FINDRISC, in adition to SAF-DM which includes SAF, age, BMI, and conditional questions on DM family history, antihypertensives, renal or cardiovascular disease events (CVE.218 persons, age 56 yr, 128M/90F, 97 with previous CVE, participated. With OGTT 28 had DM, 46 IGT, 41 impaired fasting glucose, 103 normal glucose tolerance. SAF alone revealed 23 false positives (FP, 34 false negatives (FN (sensitivity (S 68%; specificity (SP 86%. With SAF-DM, FP were reduced to 18, FN to 16 (5 with DM (S 82%; SP 89%. HbA1c scored 48 FP, 18 FN (S 80%; SP 75%. Using HbA1c-defined DM-IGT/suspicion ≥6%/42 mmol/mol, SAF-DM scored 33 FP, 24 FN (4 DM (S76%; SP72%, FPG 29 FP, 41 FN (S71%; SP80%. FINDRISC≥10 points as detection of HbA1c-based diabetes/suspicion scored 79 FP, 23 FN (S 69%; SP 45%.SAF-DM is superior to FPG and non-inferior to HbA1c to detect diabetes/IGT in intermediate-risk persons. SAF-DM's value for diabetes/IGT screening is further supported by its established performance in predicting diabetic complications.

  12. Diabetes insipidus as a rare cause of acute cognitive impairment in multiple sclerosis.

    Science.gov (United States)

    Tiedje, V; Schlamann, M; Führer, D; Moeller, L C

    2013-10-01

    Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

  13. Cardiovascular disease risk factors in a Nigerian population with impaired fasting blood glucose level and diabetes mellitus

    DEFF Research Database (Denmark)

    Oguoma, Victor M.; Nwose, Ezekiel U.; Ulasi, Ifeoma I.

    2017-01-01

    Background Diabetes is a risk factor for cardiovascular diseases (CVDs) and there are reports of increasing prevalence of prediabetes in Nigeria. This study therefore characterised CVDs risk factors in subjects with impaired fasting glucose (IFG) and diabetes. Methods Data from 4 population......-based cross-sectional studies on 2447 apparently healthy individuals from 18 - 89 years were analysed. Anthropometric, blood pressure and biochemical parameters were collected and classified. Individuals with IFG (prediabetes) and diabetes were merged each for positive cases of dyslipidaemia, high blood...... the need for risk assessment models for prediabetes and education of individuals at risk about factors that mitigate development of diabetes and CVDs....

  14. Association between hypoglycaemia and impaired hypoglycaemia awareness and mortality in people with Type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Sejling, A-S; Schouwenberg, B; Faerch, L H

    2016-01-01

    AIMS: To examine whether severe hypoglycaemia and impaired hypoglycaemic awareness, a principal predictor of severe hypoglycaemia, are associated with all-cause mortality or cardiovascular mortality in Type 1 diabetes mellitus. METHODS: Mortality was recorded in two cohorts, one in Denmark (n = 269...... of severe hypoglycaemia were prospectively recorded every month for 1 year in the Danish cohort. Follow-up data regarding mortality were obtained through medical reports and registries (Danish cohort). RESULTS: All-cause mortality was 14% (n = 39) in the Danish and 4% (n = 20) in the Dutch cohort. In either...... of macrovascular disease and reduced kidney function. CONCLUSIONS: Severe hypoglycaemia and hypoglycaemia unawareness are not associated with increased risk of all-cause or cardiovascular mortality in people with Type 1 diabetes mellitus....

  15. Endothelial progenitor cells dysfunction and impaired tissue reparation: The missed link in diabetes mellitus development.

    Science.gov (United States)

    Berezin, Alexander E

    Diabetes mellitus (DM) is considered a leading cause of premature cardiovascular (CV) mortality and morbidity in general population and in individuals with known CV disease. Recent animal and clinical studies have shown that reduced number and weak function of endothelial progenitor cells (EPCs) may not only indicate to higher CV risk, but contribute to the impaired heart and vessels reparation in patients with DM. Moreover, EPCs having a protective impact on the vasculature may mediate the functioning of other organs and systems. Therefore, EPCs dysfunction is probably promising target for DM treatment strategy, while the role of restoring of EPCs number and functionality in CV risk diminish and reduce of DM-related complications is not fully clear. The aim of the review is summary of knowledge regarding EPCs dysfunction in DM patients. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  16. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review.

    Science.gov (United States)

    Maresch, Constanze C; Stute, Dina C; Alves, Marco G; Oliveira, Pedro F; de Kretser, David M; Linn, Thomas

    2018-01-01

    Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence. This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract. A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects. A total

  17. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus.

    Science.gov (United States)

    Lee, Soo Min; Baik, Jasmine; Nguyen, Dara; Nguyen, Victoria; Liu, Shiwei; Hu, Zhaoyang; Abbott, Geoffrey W

    2017-06-01

    Type 2 diabetes mellitus (T2DM) represents a rapidly increasing threat to global public health. T2DM arises largely from obesity, poor diet, and lack of exercise, but it also involves genetic predisposition. Here we report that the KCNE2 potassium channel transmembrane regulatory subunit is expressed in human and mouse pancreatic β cells. Kcne2 deletion in mice impaired glucose tolerance as early as 5 wk of age in pups fed a Western diet, ultimately causing diabetes. In adult mice fed normal chow, skeletal muscle expression of insulin receptor β and insulin receptor substrate 1 were down-regulated 2-fold by Kcne2 deletion, characteristic of T2DM. Kcne2 deletion also caused extensive pancreatic transcriptome changes consistent with facets of T2DM, including endoplasmic reticulum stress, inflammation, and hyperproliferation. Kcne2 deletion impaired β-cell insulin secretion in vitro up to 8-fold and diminished β-cell peak outward K + current at positive membrane potentials, but also left-shifted its voltage dependence and slowed inactivation. Interestingly, we also observed an aging-dependent reduction in β-cell outward currents in both Kcne2 +/+ and Kcne2 - / - mice. Our results demonstrate that KCNE2 is required for normal β-cell electrical activity and insulin secretion, and that Kcne2 deletion causes T2DM. KCNE2 may regulate multiple K + channels in β cells, including the T2DM-linked KCNQ1 potassium channel α subunit.-Lee, S. M., Baik, J., Nguyen, D., Nguyen, V., Liu, S., Hu, Z., Abbott, G. W. Kcne2 deletion impairs insulin secretion and causes type 2 diabetes mellitus. © FASEB.

  18. Impaired glucose metabolism and type 2 diabetes in apparently healthy senior citizens.

    Science.gov (United States)

    Medina Escobar, Pedro; Moser, Michel; Risch, Lorenz; Risch, Martin; Nydegger, Urs Ernst; Stanga, Zeno

    2015-01-01

    To estimate the prevalence of unknown impaired glucose metabolism, also referred to as prediabetes (PreD), and unknown type 2 diabetes mellitus (T2DM) among subjectively healthy Swiss senior citizens. The fasting plasma glucose (FPG) and glycated haemoglobin A(1c) (HbA(1c)) levels were used for screening. A total of 1 362 subjects were included (613 men and 749 women; age range 60-99 years). Subjects with known T2DM were excluded. The FPG was processed immediately for analysis under standardised preanalytical conditions in a cross-sectional cohort study; plasma glucose levels were measured by means of the hexokinase procedure, and HbA(1c) was measured chromatographically and classified using the current American Diabetes Association (ADA) criteria. The crude prevalence of individuals unaware of having prediabetic FPG or HbA(1c) levels, was 64.5% (n = 878). Analogously, unknown T2DM was found in 8.4% (n = 114) On the basis of HbA(1c) criteria alone, significantly more subjects with unknown fasting glucose impairment and laboratory T2DM could be identified than with the FPG. The prevalence of PreD as well as of T2DM increased with age. The mean HOMA indices (homeostasis model assessment) for the different age groups, between 2.12 and 2.59, are consistent with clinically hidden disease and are in agreement with the largely orderly Body Mass Indices found in the normal range. Laboratory evidence of impaired glucose metabolism and, to a lesser extent, unknown T2DM, has a high prevalence among subjectively healthy older Swiss individuals. Laboratory identification of people with unknown out-of-range glucose values and overt diabetic hyperglycaemia might improve the prognosis by delaying the emergence of overt disease.

  19. Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: focus on vildagliptin

    Directory of Open Access Journals (Sweden)

    Russo E

    2013-04-01

    Full Text Available Eleonora Russo, Giuseppe Penno, Stefano Del Prato Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Disease, Azienda Ospedaliero Universitaria di Pisa, and University of Pisa, Pisa, Italy Background: Dipeptidyl peptidase-4 (DPP-4 inhibitors are novel classified oral anti-diabetic drugs for the treatment of type 2 diabetes mellitus (T2DM that provide important reduction in glycated hemoglobin, with a low risk for hypoglycemia and no weight gain. In T2DM patients with reduced renal function, adequate glycemic control is essential to delay the progress of kidney dysfunction, but they are at a greater risk of experiencing hypoglycemic events, especially with longer-acting sulfonylureas and meglitinides. Objective: To evaluate vildagliptin as an option to achieve glycemic control in T2DM patients with moderate or severe chronic kidney disease (CKD. Methods: A comprehensive search in the literature was performed using the term "vildagliptin." Original articles and reviews exploring our topic were carefully selected. Results: Vildagliptin provides effective glycemic control in patients with T2DM and CKD. Dose reductions are required for vildagliptin and other DPP-4 inhibitors, except linagliptin, in T2DM patients with moderate-to-severe CKD. Dose of vildagliptin had to be reduced by half (to 50 mg/day both for moderate (estimated glomerular filtration rate [eGFR] ≥30 to ≤50 mL/min and severe CKD (eGFR < 30 mL/min. Available results support a favorable efficacy, safety, and tolerability profile for vildagliptin in T2DM with moderate or severe renal failure. Preliminary data may suggest additional benefits beyond improvement of glycemic control. Conclusion: Vildagliptin can be safely used in T2DM patients with varying degrees of renal impairment. Dose adjustments for renal impairment are required. Potential long-term renal benefit of vildagliptin needs to be further explored. Keywords: type 2 diabetes mellitus, renal

  20. Relative power and coherence of EEG series are related to amnestic mild cognitive impairment in diabetes

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    Zhijie eBian

    2014-02-01

    Full Text Available Objective: Diabetes is a risk factor for dementia and mild cognitive impairment. The aim of this study was to investigate whether some features of resting-state EEG (rsEEG could be applied as a biomarker to distinguish the subjects with amnestic mild cognitive impairment (aMCI from normal cognitive function in type 2 diabetes. Materials and Methods: In this study, 28 patients with type 2 diabetes (16 aMCI patients and 12 controls were investigated. Recording of the rsEEG series and neuropsychological assessments were performed. The rsEEG signal was first decomposed into delta, theta, alpha, beta, gamma frequency bands. The relative power of each given band/sum of power and the coherence of waves from different brain areas were calculated. The extracted features from rsEEG and neuropsychological assessments were analyzed as well. Results: The main findings of this study were that: 1 compared with the control group, the ratios of power in theta band (P(theta versus power in alpha band (P(alpha (P(theta/P(alpha in the frontal region and left temporal region were significantly higher for aMCI, and 2 for aMCI, the alpha coherences in posterior, fronto-right temporal, fronto-posterior, right temporo-posterior were decreased; the theta coherences in left central-right central (LC-RC and left posterior-right posterior (LP-RP regions were also decreased; but the delta coherences in left temporal-right temporal (LT-RT region were increased. Conclusion: The proposed indexes from rsEEG recordings could be employed to track cognitive function of diabetic patients and also to help in the diagnosis of those who develop aMCI.

  1. Diabetic retinopathy and visual impairment in disaster prone coastal population of Bangladesh

    Directory of Open Access Journals (Sweden)

    M. Abu Sayeed

    2016-01-01

    Full Text Available Background and objective– Disaster prone coastal population has least accessibility to health care and very little is known about the prevalence of diabetes, diabetic retinopathy (DR and visual impairment. This study addressed the prevalence of visual impairment and DR and risk factors related to DR among population residing in disaster prone areas of Bangladesh. Methods: Thirty-two coastal communities in six coastal districts were purposively selected. All coastal people of age 18 years or more were considered eligible. Investigations included clinical history, anthropometry (height, weight, waist- and hip-girth, blood pressure and fasting blood glucose (FBG. The participants with hyperglycemia (FBG ≥5.6mmol/l were undertaken for eye examination. Visual acuity was measured bilaterally using the Snellen chart. An Early treatment diabetic retinopathy study (ETDRS cut out chart with E Optotypes was used. Results: A total of 7567 participants volunteered and 1540 had hyperglycemia (FBG ≥5.6mmol/l. Of the hyperglycemic participants, 1214 (91.7% participated for complete eye examination. Visual impairment of any type was found in 14.1%, any type cataract in 27.8% and any type DR in 18%. The participants of advancing age of higher social class and higher central obesity had excess risk for developing DR. The participants with known family history of diabetes also had greater risk. Compared with the group having FBG 5.6 – 6.9mmol/l those having FBG >6.9mmol/l had significant risk for DR (OR 3.11, 95%CI 2.04 – 4.76. Conclusion: The study concludes that visual impairment and cataract of any type is almost comparable with other coastal populations. The coastal people had higher prevalence of DR compared to rural population from other areas of Bangladesh and it was also higher than global estimate. The persons with higher age from higher social class with higher central obesity had excess risk for DR. The risk of DR increased with increasing

  2. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    Science.gov (United States)

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm 2 ). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  3. Prevalence and risk factors of diabetes and impaired fasting glucose in Nauru

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    Dan Li

    2011-09-01

    Full Text Available Abstract Background No comprehensive assessment of diabetes prevalence in Nauru has been conducted since an extreme prevalence was documented more than two decades ago. This study aims to determine the prevalence and risk factors of diabetes and impaired fasting glucose. Methods A nationwide survey in 2004 of people aged 15- 64 years (n = 1592. Fasting plasma glucose levels were used to defined diabetes (≥7.0 mmol/l or 126 mg/dl and prediabetes (6.1-6.9 mmol/l or 110-125 mg/dl. Results The sex-standardized prevalence of diabetes was 13.0% (95% CI: 10.6, 15.4 in men, 14.4% (11.9, 16.9 in women, and 13.7% (12.0, 15.4 combined. The sex-standardized prevalence of prediabetes was 6.4% (4.6, 8.2 for men, 5.5% (3.9, 7.2 for women, and 6.0% (4.8, 7.3 combined. The prevalence of diabetes for individuals 15-24, 25-34, 35-44, 45-54 and 55-64 years was 4.5%, 7.6%, 24.1%, 32.9%, and 42.7%, respectively. The prevalence of prediabetes for the same age categories was 4.2%, 8.8%, 5.9%, 6.6%, 7.1%, respectively. Multivariable, multinomial logit modeling found risk factors for prediabetes were high cholesterol levels (OR: 2.02, 95% CI: 1.66, 2.47 and elevated waist circumference (OR: 1.04, 95% CI: 1.00, 1.08, and for diabetes were age in years (OR: 1.06; 95% CI: 1.04, 1.07, cholesterol levels (OR: 1.84, 95% CI: 1.58, 2.14 and waist circumference (OR: 1.04, 95% CI: 1.02, 1.07. Conclusions Diabetes remains a major public health problem in Nauru, affecting one out of every ten people. While the prevalence of diabetes has declined, its burden has persisted among the old but also extended towards the younger age groups.

  4. Cerebral blood flow response to hypoglycemia is altered in patients with type 1 diabetes and impaired awareness of hypoglycemia.

    Science.gov (United States)

    Wiegers, Evita C; Becker, Kirsten M; Rooijackers, Hanne M; von Samson-Himmelstjerna, Federico C; Tack, Cees J; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

    2017-06-01

    It is unclear whether cerebral blood flow responses to hypoglycemia are altered in people with type 1 diabetes and impaired awareness of hypoglycemia. The aim of this study was to investigate the effect of hypoglycemia on both global and regional cerebral blood flow in type 1 diabetes patients with impaired awareness of hypoglycemia, type 1 diabetes patients with normal awareness of hypoglycemia and healthy controls ( n = 7 per group). The subjects underwent a hyperinsulinemic euglycemic-hypoglycemic glucose clamp in a 3 T MR system. Global and regional changes in cerebral blood flow were determined by arterial spin labeling magnetic resonance imaging, at the end of both glycemic phases. Hypoglycemia generated typical symptoms in patients with type 1 diabetes and normal awareness of hypoglycemia and healthy controls, but not in patients with impaired awareness of hypoglycemia. Conversely, hypoglycemia increased global cerebral blood flow in patients with impaired awareness of hypoglycemia, which was not observed in the other two groups. Regionally, hypoglycemia caused a redistribution of cerebral blood flow towards the thalamus of both patients with normal awareness of hypoglycemia and healthy controls, consistent with activation of brain regions associated with the autonomic response to hypoglycemia. No such redistribution was found in the patients with impaired awareness of hypoglycemia. An increase in global cerebral blood flow may enhance nutrient supply to the brain, hence suppressing symptomatic awareness of hypoglycemia. Altogether these results suggest that changes in cerebral blood flow during hypoglycemia contribute to impaired awareness of hypoglycemia.

  5. Determinants of developing diabetes mellitus and vascular complications in patients with impaired fasting glucose

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    Faranak Sharifi

    2013-01-01

    Full Text Available Aims: To detect the risk factors of diabetes mellitus (DM and cardiovascular complications in subjects with impaired fasting glucose (IFG. Materials and Methods: One hundred and twenty three subjects with proved IFG in Zanjan Healthy Heart Study (2002-2003 were recalled and participated in this study (2009-2010. Demographic and laboratoryinformation of the participants were collected.Ischemic heart disease (IHD was assessed by the exercise tolerance test (ETT. All the subjects with abnormal ETT or documented past history of IHD confirmed by angiographic evaluation. Ophthalmic complications including cataract, glaucoma, and diabetic retinopathy were estimated by an ophthalmologist. Results: Incidence of DM was 19.5%. All the diabetic and pre-diabetic patients had at least one of the other components of metabolic syndrome. Obesity (P: 0.04, OR: 1.8, 95%CI: 1.2-9 and low physical activity (P < 0.001, OR: 9.6, 95%CI: 3.4-32 were the only independent prognostic risk factors for progression to DM in patients with IFG. Total incidence of IHD was 14.6% and had a strong correlation with sex (P: 0.01, OR: 1.8, 95%CI: 1.2-1.5, age (P < 0.001, OR: 23, 95%CI: 2.1-67 and cigarette smoking (P < 0.001, OR: 36.5, 95%CI: 3.9-337. Non-proliferative diabetic retinopathy was shown in 2 (1.6% subjects who were all women. Conclusion: Obesity and low physical activity are the main factors of developing DM and its macrovascular complications in subjects with IFG.

  6. Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

    2016-01-01

    Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

  7. A Pilot Study of Pedestrians with Visual Impairments Detecting Traffic Gaps and Surges Containing Hybrid Vehicles.

    Science.gov (United States)

    Emerson, Robert Wall; Naghshineh, Koorosh; Hapeman, Julie; Wiener, William

    2011-03-01

    The increasing number of hybrid and quiet internal combustion engine vehicles may impact the travel abilities of pedestrians who are blind. Pedestrians who rely on auditory cues for structuring their travel may face challenges in making crossing decisions in the presence of quiet vehicles. This article describes results of initial studies looking at the crossing decisions of pedestrians who are blind at an uncontrolled crossing (no traffic control) and a light controlled intersection. The presence of hybrid vehicles was a factor in each situation. At the uncontrolled crossing, Toyota hybrids were most difficult to detect but crossing decisions were made more often in small gaps ended by a Honda hybrid. These effects were seen only at speed under 20 mph. At the light controlled intersection, parallel surges of traffic were most difficult to detect when made up only of a Ford Escape hybrid. Results suggest that more controlled studies of vehicle characteristics impacting crossing decisions of pedestrians who are blind are warranted.

  8. Ethnic variation in the prevalence of visual impairment in people attending diabetic retinopathy screening in the United Kingdom (DRIVE UK.

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    Sobha Sivaprasad

    Full Text Available To provide estimates of visual impairment in people with diabetes attending screening in a multi-ethnic population in England (United Kingdom.The Diabetic Retinopathy In Various Ethnic groups in UK (DRIVE UK Study is a cross-sectional study on the ethnic variations of the prevalence of DR and visual impairment in two multi-racial cohorts in the UK. People on the diabetes register in West Yorkshire and South East London who were screened, treated or monitored between April 2008 to July 2009 (London or August 2009 (West Yorkshire were included in the study. Data on age, gender, ethnic group, visual acuity and diabetic retinopathy were collected. Ethnic group was defined according to the 2011 census classification. The two main ethnic minority groups represented here are Blacks ("Black/African/Caribbean/Black British" and South Asians ("Asians originating from the Indian subcontinent". We examined the prevalence of visual impairment in the better eye using three cut-off points (a loss of vision sufficient for driving (approximately <6/9 (b visual impairment (<6/12 and (c severe visual impairment (<6/60, standardising the prevalence of visual impairment in the minority ethnic groups to the age-structure of the white population.Data on visual acuity and were available on 50,331 individuals 3.4% of people diagnosed with diabetes and attending screening were visually impaired (95% confidence intervals (CI 3.2% to 3.5% and 0.39% severely visually impaired (0.33% to 0.44%. Blacks and South Asians had a higher prevalence of visual impairment (directly age standardised prevalence 4.6%, 95% CI 4.0% to 5.1% and 6.9%, 95% CI 5.8% to 8.0% respectively compared to white people (3.3%, 95% CI 3.1% to 3.5%. Visual loss was also more prevalent with increasing age, type 1 diabetes and in people living in Yorkshire.Visual impairment remains an important public health problem in people with diabetes, and is more prevalent in the minority ethnic groups in the UK.

  9. The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals.

    Science.gov (United States)

    Sang, Yu Ming; Wang, Li Jun; Mao, Hong Xian; Lou, Xue Yong; Zhu, Yi Jun

    2018-06-01

    This study assessed short-term memory and biochemical indicators with the levels of ghrelin, leptin, and cortisol between cognitive impairment and normal older adults with or without diabetes. We enrolled 286 older adults (aged 65-85 years) with or without diabetes from the local community. Short-term memory was assessed using pictures of common objects; cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The physiological indexes assessed were plasma levels of fasting ghrelin and leptin, ghrelin level at 2_h after breakfast, 24-h urinary cortisol value, body mass index, and plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. In both non-diabetic and diabetic subjects, short-term memory was significantly lower in the impaired cognition group (5.99 ± 2.90 in non-diabetic subjects and 4.71 ± 2.14 in diabetic subjects) than in the normal cognition group (8.14 ± 2.23 in non-diabetic subjects and 7.82 ± 3.37 in diabetic subjects). Baseline ghrelin level was significantly lower in the impaired cognition group (9.07 ± 1.13 ng/mL in non-diabetic subjects and 7.76 ± 1.34 ng/mL in diabetic subjects) than in the normal cognition group (10.94 ± 1.53 ng/mL in non-diabetic subjects and 9.93 ± 1.76 ng/mL in diabetic subjects); plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. were significantly higher in the impaired cognition group than in the normal cognition group, while no significant difference was observed in plasma levels of fasting leptin between different groups. Fasting plasma ghrelin and cortisol levels may be markers of cognitive decline and memory loss. It is possible that adjusting their levels may have a therapeutic effect, and this should be investigated in future studies.

  10. Interactive relations of type 2 diabetes and abdominal obesity to cognitive impairment: A cross-sectional study in rural area of Xi'an in China.

    Science.gov (United States)

    Li, Yanbo; Shang, Suhang; Fei, Yulang; Chen, Chen; Jiang, Yu; Dang, Liangjun; Liu, Jie; Ma, Louyan; Wei, Meng; Qu, Qiumin

    2018-01-01

    Type 2 diabetes and obesity, which are frequently comorbid, have been associated with cognitive impairment. We aim to examine the potential modulating effect between obesity and diabetes on cognitive impairment. We recruited 865 adults (aged ≥55years) lived in a village of Xi'an in China from October 2014 to March 2015. All participants underwent biomedical and neuropsychological assessment. Relations of diabetes and abdominal obesity to cognitive impairment were examined in multiple regression models. A total of 155 participants (17.9%) presented with the diagnosis of cognitive impairment. Diabetes or obesity alone wasn't significantly associated with cognitive impairment. Interaction analysis showed a significant interaction between abdominal obesity and diabetes on cognitive impairment. Stratified multivariate analysis revealed that the association between diabetes and cognitive impairment was positive in participants with abdominal obesity (OR 2.436, 95% CI 1.345-4.411, p=0.003, in diabetics with high WC, and OR 2.348, 95% CI 1.373-4.014, p=0.002, in diabetics with high WHR), but negative in those without abdominal obesity. Type 2 diabetes interacts with abdominal obesity to be associated with an increased risk of cognitive impairment by more than two times. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Association between urinary albumin excretion and intraocular pressure in type 2 diabetic patients without renal impairment.

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    Jin A Choi

    Full Text Available BACKGROUND: To assess the relationship between urinary albumin excretion and intraocular pressure (IOP in type 2 diabetes patients without renal impairment. METHODS: We explored the effects of albuminuria on high IOP in 402 non-glaucomatous type 2 diabetes without renal impairment who participated in the 2011 Korean National Health and Nutrition Examination Survey (KNHANES. Multiple logistic regression analysis was used to assess the relationship between log-transformed albumin/creatinine ratio (ACR tertiles and an IOP of ≥ 18 mmHg after adjusting for age, gender, hypertension, body mass index, triglycerides, area of residence, and education level. RESULTS: Subjects with a high IOP ≥ 18 mmHg were more likely to be current smokers (P = 0.038, heavy drinkers (P = 0.006, and to have high systolic blood pressure (P = 0.016, triglycerides (P = 0.008, and a higher log-transformed ACR (P = 0.022.In multivariate regression analysis, ACR tertile was associated with the prevalence of high IOP significantly (P = 0.022. The associations between ACR tertiles and high IOP were significant in overweight patients and those with abdominal obesity (P = 0.003 and 0.003, respectively. In contrast, there were no associations in the subgroup of patients who were not overweight and those without abdominal obesity (P = 0.291 and 0.561, respectively. CONCLUSIONS: Urinary albumin excretion is associated with high IOP in the type 2 diabetes population without renal insufficiency. The effect of the albuminuria on IOP was evident in a subgroup of patients with components of metabolic syndrome.

  12. Expression and activity of arginase isoenzymes during normal and diabetes-impaired skin repair.

    Science.gov (United States)

    Kämpfer, Heiko; Pfeilschifter, Josef; Frank, Stefan

    2003-12-01

    Within the past years, an important role for nitric oxide (NO) in skin repair has been well defined. As NO is synthesized from L-arginine by NO synthases (NOS), the availability of L-arginine might be one rate-limiting factor of NO production at the wound site. Upon injury, arginase-1 and -2 mRNA, protein, and activity were strongly induced reaching a maximum between day 3 and day 7 postwounding. Immunohistochemistry colocalized both arginases and the inducible NOS (iNOS) at epithelial sites at the margins of the wound. Notably, diabetes-impaired skin repair in leptin-deficient mice (diabetes/diabetes, db/db; and obese/obese, ob/ob) was characterized by an abnormally elevated arginase activity in wound tissue in the absence of an expression of iNOS. Expression analyses demonstrated that arginase-1 contributed to increased arginase activities in impaired repair. Interestingly, an improved healing of chronic wound situations in leptin-supplemented ob/ob mice was strongly associated with an adjustment of the dysregulated expression of L-arginine-converting enzymes: an attenuated iNOS expression was upregulated early in repair and an augmented arginase-1 expression and activity was downregulated in the presence of markedly elevated numbers of macrophages during late repair. These data suggest a coordinated consumption of L-arginine by the NOS and arginase enzymatic pathways at the wound site as a prerequisite for a balanced NO (via iNOS) and polyamine (via arginases) synthesis that drives a normal skin repair.

  13. A Pilot Study of Pedestrians with Visual Impairments Detecting Traffic Gaps and Surges Containing Hybrid Vehicles

    Science.gov (United States)

    Emerson, Robert Wall; Naghshineh, Koorosh; Hapeman, Julie; Wiener, William

    2010-01-01

    The increasing number of hybrid and quiet internal combustion engine vehicles may impact the travel abilities of pedestrians who are blind. Pedestrians who rely on auditory cues for structuring their travel may face challenges in making crossing decisions in the presence of quiet vehicles. This article describes results of initial studies looking at the crossing decisions of pedestrians who are blind at an uncontrolled crossing (no traffic control) and a light controlled intersection. The presence of hybrid vehicles was a factor in each situation. At the uncontrolled crossing, Toyota hybrids were most difficult to detect but crossing decisions were made more often in small gaps ended by a Honda hybrid. These effects were seen only at speed under 20 mph. At the light controlled intersection, parallel surges of traffic were most difficult to detect when made up only of a Ford Escape hybrid. Results suggest that more controlled studies of vehicle characteristics impacting crossing decisions of pedestrians who are blind are warranted. PMID:21379367

  14. Ethyl acetate fraction from Hibiscus sabdariffa L. attenuates diabetes-associated cognitive impairment in mice.

    Science.gov (United States)

    Seung, Tae Wan; Park, Seon Kyeong; Kang, Jin Yong; Kim, Jong Min; Park, Sang Hyun; Kwon, Bong Seok; Lee, Chang Jun; Kang, Jeong Eun; Kim, Dae Ok; Lee, Uk; Heo, Ho Jin

    2018-03-01

    The ameliorating effects of the ethyl acetate fraction from Hibiscus sabdariffa L. (EFHS) 2 against diabetes mellitus (DM) 3 and DM-induced cognitive impairment were investigated on streptozotocin (STZ) 4 -induced DM mice. The EFHS groups showed improved hyperglycemia and glucose tolerance compared to the STZ group. Furthermore, their liver and kidney function and lipid metabolic imbalance in the blood serum were effectively recovered. The EFHS groups significantly ameliorated STZ-induced cognitive impairment in Y-maze, passive avoidance, and Morris water maze (MWM) 5 tests. The EFHS groups showed significant improvement in the antioxidant and cholinergic systems of the brain tissue. In addition, EFHS had an excellent ameliorating effect on protein expression levels from the tau hyperphosphorylation pathways, such as phospho-c-Jun N-terminal kinases (p-JNK), 6 phospho-tau (p-tau), 7 and cleaved poly (ADP-ribose) polymerase (c-PARP). 8 The main compounds of EFHS were identified as various phenolic compounds, including hibiscus acid, caffeoylquinic acid (CQA) 9 isomers, and quercetin derivates. Therefore, EFHS containing various physiologically active materials can potentially be used for improving DM-induced cognitive impairment via its antioxidant activity, improvement of the cholinergic system, and hyperphosphorylation tau signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice.

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    João M N Duarte

    Full Text Available Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1 and A(2A receptors emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25, mainly glutamatergic (vesicular glutamate transporters, and increased astrogliosis (GFAP immunoreactivity compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A receptors and down-regulated A(1 receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.

  16. Caffeine consumption prevents diabetes-induced memory impairment and synaptotoxicity in the hippocampus of NONcZNO10/LTJ mice.

    Science.gov (United States)

    Duarte, João M N; Agostinho, Paula M; Carvalho, Rui A; Cunha, Rodrigo A

    2012-01-01

    Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7-11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A(2A) receptors and down-regulated A(1) receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes.

  17. Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hwanjeong; Choi, Sehun; Han, Yeonhee [Research Institute of Chonbuk National Univ. Medical School and Hospitial, Jeonju (Korea, Republic of); Lee, Dong Soo; Lee, Hoyoung; Chung, Junekey [Seoul National Univ., Seoul (Korea, Republic of)

    2013-09-15

    This study aimed at identifying the predictive parameters on quantitative gated myocardial perfusion single-photon emission computed tomography (QG-SPECT) in diabetic patients with normal perfusion but impaired function. Methods Among the 533 consecutive diabetic patients, 379 patients with normal perfusion on rest Tl-201/dipyridamole-stress Tc-{sup 99m} sestamibi Gated SPECT were enrolled. Patients were grouped into those with normal post-stress left ventricular function (Group I) and those with impaired function (EF <50 or impaired regional wall motion, Group II). We investigated cardiac events and cause of death by chart review and telephone interview. Survival analysis and Cox proportional hazard model analysis were performed. Between the Group I and II, cardiac events as well as chest pain symptoms, smoking, diabetic complications were significantly different (P<0.05). On survival analysis, event free survival rate in Group II was significantly lower than in Group I (P=0.016). In univariate Cox proportional hazard analysis on overall cardiac event, Group (II over I), diabetic nephropathy, summed motion score (SMS), summed systolic thickening score (STS), numbers of abnormal segmental wall motion and systolic thickening predicted more cardiac events (P<0.05). Multivariate analysis showed that STS was the only independent predictor cardiac event. The functional parameter, especially summed systolic thickening score on QG-SPECT had prognostic values, despite normal perfusion, in predicting cardiac events in diabetic patients, and QG-SPECT provides clinically useful risk stratification in diabetic patients with normal perfusion.

  18. Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients

    OpenAIRE

    Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

    2017-01-01

    Background and aims People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. Results In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghre...

  19. Impaired Coronary and Renal Vascular Function in Spontaneously Type 2 Diabetic Leptin-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Helena U Westergren

    Full Text Available Type 2 diabetes is associated with macro- and microvascular complications in man. Microvascular dysfunction affects both cardiac and renal function and is now recognized as a main driver of cardiovascular mortality and morbidity. However, progression of microvascular dysfunction in experimental models is often obscured by macrovascular pathology and consequently demanding to study. The obese type 2 diabetic leptin-deficient (ob/ob mouse lacks macrovascular complications, i.e. occlusive atherosclerotic disease, and may therefore be a potential model for microvascular dysfunction. The present study aimed to test the hypothesis that these mice with an insulin resistant phenotype might display microvascular dysfunction in both coronary and renal vascular beds.In this study we used non-invasive Doppler ultrasound imaging to characterize microvascular dysfunction during the progression of diabetes in ob/ob mice. Impaired coronary flow velocity reserve was observed in the ob/ob mice at 16 and 21 weeks of age compared to lean controls. In addition, renal resistivity index as well as pulsatility index was higher in the ob/ob mice at 21 weeks compared to lean controls. Moreover, plasma L-arginine was lower in ob/ob mice, while asymmetric dimethylarginine was unaltered. Furthermore, a decrease in renal vascular density was observed in the ob/ob mice.In parallel to previously described metabolic disturbances, the leptin-deficient ob/ob mice also display cardiac and renal microvascular dysfunction. This model may therefore be suitable for translational, mechanistic and interventional studies to improve the understanding of microvascular complications in type 2 diabetes.

  20. Diabetes in sub-Saharan Africa – from policy to practice to progress: targeting the existing gaps for future care for diabetes

    Science.gov (United States)

    Pastakia, Sonak D; Pekny, Chelsea R; Manyara, Simon M; Fischer, Lydia

    2017-01-01

    The global prevalence and impact of diabetes has increased dramatically, particularly in sub-Saharan Africa. This region faces unique challenges in combating the disease including lack of funding for noncommunicable diseases, lack of availability of studies and guidelines specific to the population, lack of availability of medications, differences in urban and rural patients, and inequity between public and private sector health care. Because of these challenges, diabetes has a greater impact on morbidity and mortality related to the disease in sub-Saharan Africa than any other region in the world. In order to address these unacceptably poor trends, contextualized strategies for the prevention, identification, management, and financing of diabetes care within this population must be developed. This narrative review provides insights into the policy landscape, epidemiology, pathophysiology, care protocols, medication availability, and health care systems to give readers a comprehensive summary of many factors in these domains as they pertain to diabetes in sub-Saharan Africa. In addition to providing a review of the current evidence available in these domains, potential solutions to address the major gaps in care will be proposed to reverse the negative trends seen with diabetes in sub-Saharan Africa. PMID:28790858

  1. Korean Red Ginseng Improves Glucose Control in Subjects with Impaired Fasting Glucose, Impaired Glucose Tolerance, or Newly Diagnosed Type 2 Diabetes Mellitus

    OpenAIRE

    Bang, Hyangju; Kwak, Jung Hyun; Ahn, Hyeon Yeong; Shin, Dong Yeob; Lee, Jong Ho

    2014-01-01

    This study was designed to evaluate the effect of Korean red ginseng (KRG) supplementation on glucose control in subjects with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or newly diagnosed type 2 diabetes mellitus (T2DM). The study was a 12-week randomized, double-blinded, placebo-controlled (5 g of KRG [n=21] or placebo [n=20] in tablet form) trial. Glucose-related biomarkers, including serum and whole blood levels of glucose, insulin, and C-peptide, were measured by 2...

  2. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat

    NARCIS (Netherlands)

    Visser, J. T. J.; Lammers, K.; Hoogendijk, A.; Boer, M. W.; Brugman, S.; Beijer-Liefers, S.; Zandvoort, A.; Harmsen, H.; Welling, G.; Stellaard, F.; Bos, N. A.; Fasano, A.; Rozing, J.

    2010-01-01

    Aims/hypothesis Impaired intestinal barrier function is observed in type I diabetes patients and animal models of the disease. Exposure to diabetogenic antigens from the intestinal milieu due to a compromised intestinal barrier is considered essential for induction of the autoimmune process leading

  3. Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes

    Science.gov (United States)

    McNay, Ewan C.; Recknagel, Andrew K.

    2011-01-01

    Understanding of the role of insulin in the brain has gradually expanded, from initial conceptions of the brain as insulin-insensitive through identification of a role in regulation of feeding to recent demonstration of insulin as a key component of hippocampal memory processes. Conversely, systemic insulin resistance such as that seen in type 2 diabetes is associated with a range of cogntive and neural deficits. Here we review the evidence for insulin as a cognitive and neural modulator, including potential effector mechanisms, and examine the impact that type 2 diabetes has on these mechanisms in order to identify likely bases for the cognitive impairments seen in type 2 diabetic patients. PMID:21907815

  4. Muscle Oxygen Supply Impairment during Exercise in Poorly Controlled Type 1 Diabetes

    Science.gov (United States)

    TAGOUGUI, SEMAH; LECLAIR, ERWAN; FONTAINE, PIERRE; MATRAN, RÉGIS; MARAIS, GAELLE; AUCOUTURIER, JULIEN; DESCATOIRE, AURÉLIEN; VAMBERGUE, ANNE; OUSSAIDENE, KAHINA; BAQUET, GEORGES; HEYMAN, ELSA

    2015-01-01

    ABSTRACT Purpose Aerobic fitness, as reflected by maximal oxygen (O2) uptake (V˙O2max), is impaired in poorly controlled patients with type 1 diabetes. The mechanisms underlying this impairment remain to be explored. This study sought to investigate whether type 1 diabetes and high levels of glycated hemoglobin (HbA1c) influence O2 supply including O2 delivery and release to active muscles during maximal exercise. Methods Two groups of patients with uncomplicated type 1 diabetes (T1D-A, n = 11, with adequate glycemic control, HbA1c 8%) were compared with healthy controls (CON-A, n = 11; CON-I, n = 12, respectively) matched for physical activity and body composition. Subjects performed exhaustive incremental exercise to determine V˙O2max. Throughout the exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin in the vastus lateralis. Venous and arterialized capillary blood was sampled during exercise to assess arterial O2 transport and factors able to shift the oxyhemoglobin dissociation curve. Results Arterial O2 content was comparable between groups. However, changes in total hemoglobin (i.e., muscle blood volume) was significantly lower in T1D-I compared with that in CON-I. T1D-I also had impaired changes in deoxyhemoglobin levels and increase during high-intensity exercise despite normal erythrocyte 2,3-diphosphoglycerate levels. Finally, V˙O2max was lower in T1D-I compared with that in CON-I. No differences were observed between T1D-A and CON-A. Conclusions Poorly controlled patients displayed lower V˙O2max and blunted muscle deoxyhemoglobin increase. The latter supports the hypotheses of increase in O2 affinity induced by hemoglobin glycation and/or of a disturbed balance between nutritive and nonnutritive muscle blood flow. Furthermore, reduced exercise muscle blood volume in poorly controlled patients may warn clinicians of microvascular dysfunction occurring even before overt

  5. High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling.

    Science.gov (United States)

    Qi, Weiwei; Yang, Chuan; Dai, Zhiyu; Che, Di; Feng, Juan; Mao, Yuling; Cheng, Rui; Wang, Zhongxiao; He, Xuemin; Zhou, Ti; Gu, Xiaoqiong; Yan, Li; Yang, Xia; Ma, Jian-Xing; Gao, Guoquan

    2015-04-01

    Diabetic foot ulcer (DFU) caused by impaired wound healing is a common vascular complication of diabetes. The current study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contribute to skin wound-healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved the functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF-deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous microvessels, increased skin thickness, improved numbers and functions of circulating EPCs, and accelerated wound healing compared with wild-type mice. Overexpression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation downstream of the PEDF interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound-healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing in the process of angiogenesis and vasculogenesis through the inhibition of Wnt/β-catenin signaling. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Pathophysiology and aetiology of impaired fasting glycaemia and impaired glucose tolerance: does it matter for prevention and treatment of type 2 diabetes?

    DEFF Research Database (Denmark)

    Faerch, K; Borch-Johnsen, K; Holst, Jens Juul

    2009-01-01

    Prior to the development of type 2 diabetes, glucose levels increase into the prediabetic states of isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), or combined IFG/IGT. A better understanding of the aetiology and pathophysiology of the prediabetic states...... might give a basis for the development of individualised prevention and treatment strategies for type 2 diabetes. Several studies have examined mechanisms and potential aetiological factors leading to the development of the different prediabetic states. The pathophysiology of i-IFG seems to include...... the following key defects: reduced hepatic insulin sensitivity, stationary beta cell dysfunction and/or chronic low beta cell mass, altered glucagon-like peptide-1 secretion and inappropriately elevated glucagon secretion. Conversely, the prediabetic state i-IGT is characterised by reduced peripheral insulin...

  7. Dysregulated LIF-STAT3 pathway is responsible for impaired embryo implantation in a Streptozotocin-induced diabetic mouse model

    Directory of Open Access Journals (Sweden)

    Tong-Song Wang

    2015-07-01

    Full Text Available The prevalence of diabetes is increasing worldwide with the trend of patients being young and creating a significant burden on health systems, including reproductive problems, but the effects of diabetes on embryo implantation are still poorly understood. Our study was to examine effects of diabetes on mouse embryo implantation, providing experimental basis for treating diabetes and its complications. Streptozotocin (STZ was applied to induce type 1 diabetes from day 2 of pregnancy or pseudopregnancy in mice. Embryo transfer was used to analyze effects of uterine environment on embryo implantation. Our results revealed that the implantation rate is significantly reduced in diabetic mice compared to controls, and the change of uterine environment is the main reason leading to the decreased implantation rate. Compared to control, the levels of LIF and p-STAT3 are significantly decreased in diabetic mice on day 4 of pregnancy, and serum estrogen level is significantly higher. Estrogen stimulates LIF expression under physiological level, but the excessive estrogen inhibits LIF expression. LIF, progesterone or insulin supplement can rescue embryo implantation in diabetic mice. Our data indicated that the dysregulated LIF-STAT3 pathway caused by the high level of estrogen results in the impaired implantation in diabetic mice, which can be rescued by LIF, progesterone or insulin supplement.

  8. Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide

    Directory of Open Access Journals (Sweden)

    Zhongjian Cheng

    2018-06-01

    Full Text Available Insufficient hydrogen sulfide (H2S has been implicated in Type 2 diabetic mellitus (T2DM and hyperhomocysteinemia (HHcy-related cardiovascular complications. We investigated the role of H2S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA of db/db mice fed a high methionine (HM diet. HM diet (8 weeks induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively, and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF-induced endothelium-dependent relaxation to acetylcholine (ACh, determined by the presence of eNOS inhibitor N(ω-nitro-L-arginine methyl ester (L-NAME and prostacyclin (PGI2 inhibitor indomethacin (INDO, in SMA from db/db mice but not that from db/+ mice. A non-selective Ca2+-active potassium channel (KCa opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective KCa blocker TEA and intermediate-conductance KCa blocker (IKCa Tram-34, but not by small-conductance KCa (SKCa blocker Apamin. HHcy potentiated the reduction of free sulfide, H2S and cystathionine γ-lyase protein, which converts L-cysteine to H2S, in SMA of db/db mice. Importantly, a stable H2S donor DATS diminished the enhanced O2- production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IKCa tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by KCa blockers. Conclusions: Intermediate HHcy potentiated H2S reduction via CSE-downregulation in microvasculature of T2DM mice. H2S is justified as an EDHF. Insufficient H2S

  9. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Science.gov (United States)

    Toque, Haroldo A; Nunes, Kenia P; Yao, Lin; Xu, Zhimin; Kondrikov, Dmitry; Su, Yunchao; Webb, R Clinton; Caldwell, Ruth B; Caldwell, R William

    2013-01-01

    Elevated arginase (Arg) activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC) from Akita mice. Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT) mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP) was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC) compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH) reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177) (in aorta and CC) and nNOS expression (in CC) were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks. Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  10. Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and impaired vascular endothelial and nitrergic function.

    Directory of Open Access Journals (Sweden)

    Haroldo A Toque

    Full Text Available Elevated arginase (Arg activity is reported to be involved in diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine availability to nitric oxide (NO synthase (NOS and NO production. Akita mice, a genetic non-obese type 1 diabetes model, recapitulate human diabetes. We determined the role of Arg in a time-course of diabetes-associated endothelial dysfunction in aorta and corpora cavernosa (CC from Akita mice.Endothelium-dependent relaxation, Arg and NOS activity, and protein expression levels of Arg and constitutive NOS were assessed in aortas and CC from Akita and non-diabetic wild type (WT mice at 4, 12 and 24 wks of age. Systolic blood pressure (SBP was assessed by tail cuff. In aorta and CC, Akita mice exhibited a progressive impairment of vascular endothelial and nitrergic function increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in CC compared with that of age-matched WT mice. Treatment of aorta and CC from Akita mice with an Arg inhibitor (BEC or ABH reduced diabetes-induced elevation of Arg activity and restored endothelial and nitrergic function. Reduced levels of phospho-eNOS at Ser(1177 (in aorta and CC and nNOS expression (in CC were observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment. Further, Akita mice exhibited moderately increased SBP at 24 wks and increased sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation in CC at 12 and 24 wks.Over 24 wks of diabetes in Akita mice, both aortic and cavernosal tissues exhibited increased Arg activity/expression, contributing to impaired endothelial and nitrergic function and reduced NO production. Our findings demonstrate involvement of Arg activity in diabetes-induced impairment of vascular function in Akita mouse.

  11. Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 diabetes: a prospective cohort study.

    Science.gov (United States)

    Ligthart, Symen; van Herpt, Thijs T W; Leening, Maarten J G; Kavousi, Maryam; Hofman, Albert; Stricker, Bruno H C; van Hoek, Mandy; Sijbrands, Eric J G; Franco, Oscar H; Dehghan, Abbas

    2016-01-01

    Data are scarce for the lifetime risk of developing impaired glucose metabolism, including prediabetes, as are data for the risk of eventual progression from prediabetes to diabetes and for initiation of insulin treatment in previously untreated patients with diabetes. We aimed to calculate the lifetime risk of the full range of glucose impairments, from normoglycaemia to prediabetes, type 2 diabetes, and eventual insulin use. In this prospective population-based cohort analysis, we used data from the population-based Rotterdam Study. We identified diagnostic events by use of general practitioners' records, hospital discharge letters, pharmacy dispensing data, and serum fasting glucose measurements taken at the study centre (Rotterdam, Netherlands) visits. Normoglycaemia, prediabetes, and diabetes were defined on the basis of WHO criteria for fasting glucose (normoglycaemia: ≤6·0 mmol/L; prediabetes: >6·0 mmol/L and prediabetes to overt diabetes and from diabetes free of insulin treatment to insulin use. Additionally, we calculated years lived with healthy glucose metabolism. We used data from 10 050 participants from the Rotterdam Study. During a follow-up of up to 14·7 years (between April 1, 1997, and Jan 1, 2012), 1148 participants developed prediabetes, 828 developed diabetes, and 237 started insulin treatment. At age 45 years, the remaining lifetime risk was 48·7% (95% CI 46·2-51·3) for prediabetes, 31·3% (29·3-33·3) for diabetes, and 9·1% (7·8-10·3) for insulin use. In individuals aged 45 years, the lifetime risk to progress from prediabetes to diabetes was 74·0% (95% CI 67·6-80·5), and 49·1% (38·2-60·0) of the individuals with overt diabetes at this age started insulin treatment. The lifetime risks attenuated with advancing age, but increased with increasing BMI and waist circumference. On average, individuals with severe obesity lived 10 fewer years without glucose impairment compared with normal-weight individuals. Impaired glucose

  12. Impaired cerebral blood flow and oxygenation during exercise in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Kim, Yu-Sok; Seifert, Thomas; Brassard, Patrice

    2015-01-01

    Endothelial vascular function and capacity to increase cardiac output during exercise are impaired in patients with type 2 diabetes (T2DM). We tested the hypothesis that the increase in cerebral blood flow (CBF) during exercise is also blunted and, therefore, that cerebral oxygenation becomes...... affected and perceived exertion increased in T2DM patients. We quantified cerebrovascular besides systemic hemodynamic responses to incremental ergometer cycling exercise in eight male T2DM and seven control subjects. CBF was assessed from the Fick equation and by transcranial Doppler-determined middle...... at higher workloads in T2DM patients and their work capacity and increase in cardiac output were only ~80% of that established in the control subjects. CBF and cerebral oxygenation were reduced during exercise in T2DM patients (P

  13. Diabetes-impaired wound healing is improved by matrix therapy with heparan sulfate glycosaminoglycan mimetic OTR4120 in rats

    NARCIS (Netherlands)

    M. Tong (Miao); B. Tuk (Bastiaan); P. Shang (Peng); J.M. Hekking-Weijma (Ineke); E.M.G. Fijneman (Esther ); M. Guijt (Marnix); S.E.R. Hovius (Steven); J.W. van Neck (Han)

    2012-01-01

    textabstractWound healing in diabetes is frequently impaired, and its treatment remains a challenge. We tested a therapeutic strategy of potentiating intrinsic tissue regeneration by restoring the wound cellular environment using a heparan sulfate glycosaminoglycan mimetic, OTR4120. The effect of

  14. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing

    Science.gov (United States)

    Hoke, Glenn D.; Ramos, Corrine; Hoke, Nicholas N.; Crossland, Mary C.; Shawler, Lisa G.

    2016-01-01

    Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer. PMID:27840833

  15. Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

    Science.gov (United States)

    Dayeh, Tasnim; Ling, Charlotte

    2015-10-01

    β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.

  16. Atypical Diabetic Foot Ulcer Keratinocyte Protein Signaling Correlates with Impaired Wound Healing.

    Science.gov (United States)

    Hoke, Glenn D; Ramos, Corrine; Hoke, Nicholas N; Crossland, Mary C; Shawler, Lisa G; Boykin, Joseph V

    2016-01-01

    Diabetes mellitus is associated with chronic diabetic foot ulcers (DFUs) and wound infections often resulting in lower extremity amputations. The protein signaling architecture of the mechanisms responsible for impaired DFU healing has not been characterized. In this preliminary clinical study, the intracellular levels of proteins involved in signal transduction networks relevant to wound healing were non-biasedly measured using reverse-phase protein arrays (RPPA) in keratinocytes isolated from DFU wound biopsies. RPPA allows for the simultaneous documentation and assessment of the signaling pathways active in each DFU. Thus, RPPA provides for the accurate mapping of wound healing pathways associated with apoptosis, proliferation, senescence, survival, and angiogenesis. From the study data, we have identified potential diagnostic, or predictive, biomarkers for DFU wound healing derived from the ratios of quantified signaling protein expressions within interconnected pathways. These biomarkers may allow physicians to personalize therapeutic strategies for DFU management on an individual basis based upon the signaling architecture present in each wound. Additionally, we have identified altered, interconnected signaling pathways within DFU keratinocytes that may help guide the development of therapeutics to modulate these dysregulated pathways, many of which parallel the therapeutic targets which are the hallmarks of molecular therapies for treating cancer.

  17. Diabetes guidelines and clinical practice: is there a gap? The South ...

    African Journals Online (AJOL)

    Objectives: The objective of this survey was to determine the therapeutic management of patients with diabetes in the South African private healthcare environment. Design: The International Diabetes Management Practices Study is an international multicentre and observational study. In this paper, the local South African ...

  18. Diabetes guidelines and clinical practice: is there a gap? The South ...

    African Journals Online (AJOL)

    2012-01-03

    Jan 3, 2012 ... Original Research: Diabetes guidelines and clinical practice. 85. 2012 Volume 17 No 2 ... endorsed by The Society of Endocrinology Metabolism and Diabetes of ... do not reach the target HbA1c value of < 7%.8-10 In striving to achieve ..... reflected the worst glycaemic control, as assessed by HbA1c levels.

  19. Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

    Science.gov (United States)

    Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

    2013-05-01

    The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

  20. Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

    Science.gov (United States)

    Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

    2012-01-01

    Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960

  1. Lipopolysaccharide regulated protein expression is only partly impaired in monocytes from patients with type I diabetes

    Directory of Open Access Journals (Sweden)

    Abke Sabine

    2006-03-01

    Full Text Available Abstract Background Monocytes play an important role in innate immunity and atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS activated monocytes from type 1 diabetes (T1D patients has been described and may contribute to the impaired inflammatory response in these individuals. In the present study the influence of LPS on five different proteins with a function in immunity and atherosclerosis was analyzed in monocytes from controls and T1D patients. Methods Monocytes were isolated from controls and T1D patients and the LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP-1 and superoxide dismutase (SOD 2, as well as the LPS-mediated decrease of apolipoprotein E (Apo E in primary human monocytes from controls and T1D patients was determined. Results CCL2 and IL-6 secretion in response to LPS was found significantly reduced in monocytes from T1D patients when compared to controls whereas basal CCL2 release was similar in control and T1D cells. In contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS stimulation is similar from T1D and control monocytes. Conclusion These data indicate that LPS-mediated protein expression is only partly disturbed in monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated monocytes of these patients may contribute to an impaired inflammatory response and vascular disease.

  2. Impaired Word and Face Recognition in Older Adults with Type 2 Diabetes.

    Science.gov (United States)

    Jones, Nicola; Riby, Leigh M; Smith, Michael A

    2016-07-01

    Older adults with type 2 diabetes mellitus (DM2) exhibit accelerated decline in some domains of cognition including verbal episodic memory. Few studies have investigated the influence of DM2 status in older adults on recognition memory for more complex stimuli such as faces. In the present study we sought to compare recognition memory performance for words, objects and faces under conditions of relatively low and high cognitive load. Healthy older adults with good glucoregulatory control (n = 13) and older adults with DM2 (n = 24) were administered recognition memory tasks in which stimuli (faces, objects and words) were presented under conditions of either i) low (stimulus presented without a background pattern) or ii) high (stimulus presented against a background pattern) cognitive load. In a subsequent recognition phase, the DM2 group recognized fewer faces than healthy controls. Further, the DM2 group exhibited word recognition deficits in the low cognitive load condition. The recognition memory impairment observed in patients with DM2 has clear implications for day-to-day functioning. Although these deficits were not amplified under conditions of increased cognitive load, the present study emphasizes that recognition memory impairment for both words and more complex stimuli such as face are a feature of DM2 in older adults. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  3. The impaired myocardial ischemic tolerance in adult offspring of diabetic pregnancy is restored by maternal melatonin treatment.

    Science.gov (United States)

    Gao, Ling; Zhao, Yi-Chao; Liang, Yan; Lin, Xian-Hua; Tan, Ya-Jing; Wu, Dan-Dan; Li, Xin-Zhu; Ye, Bo-Zhi; Kong, Fan-Qi; Sheng, Jian-Zhong; Huang, He-Feng

    2016-10-01

    Diabetic pregnancy, with ever increasing prevalence, adversely affects embryogenesis and increases vasculometabolic disorder risks in adult offspring. However, it remains poorly understood whether maternal diabetes increases the offspring's susceptibility to heart injuries in adulthood. In this study, we observed that cardiac function and structure were comparable between adult offspring born to diabetic mice and their counterparts born to nondiabetic mice at baseline. However, in response to myocardial ischemia/reperfusion (MIR), diabetic mother offspring exhibited augmented infarct size, cardiac dysfunction, and myocardial apoptosis compared with control, in association with exaggerated activation of mitochondria- and endoplasmic reticulum (ER) stress-mediated apoptosis pathways and oxidative stress. Molecular analysis showed that the impaired myocardial ischemic tolerance in diabetic mother offspring was mainly attributable to blunted cardiac insulin receptor substrate (IRS)-1/Akt signaling. Furthermore, the effect of maternal melatonin administration on offspring's response to MIR was determined, and the results indicated that melatonin treatment in diabetic dams during pregnancy significantly improved the tolerance to MIR injury in their offspring, via restoring cardiac IRS-1/Akt signaling. Taken together, these data suggest that maternal diabetes predisposes offspring to augmented MIR injury in adulthood, and maternal melatonin supplementation during diabetic pregnancy may hold promise for improving myocardial ischemic tolerance in the offspring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Science.gov (United States)

    Lukashevich, Valentina; Schweizer, Anja; Foley, James E; Dickinson, Sheila; Groop, Per-Henrik; Kothny, Wolfgang

    2013-01-01

    Background The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo), all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent) for longstanding type 2 diabetes (mean approximately 19 years). Results With vildagliptin in combination with insulin, the adjusted mean change (AMΔ) in HbA1c from baseline (7.7% ± 0.1%) was −0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo) was −0.6% ± 0.2% (P vildagliptin than placebo (45.2% versus 22.8%, P = 0.008). When added to insulin, vildagliptin and placebo had comparable hypoglycemic profiles and did not cause weight gain. Both treatments were similarly well tolerated, with comparable incidences of adverse events, serious adverse events, and deaths. Conclusion When added to insulin therapy in patients with severe renal impairment and longstanding type 2 diabetes, vildagliptin 50 mg once daily was efficacious, eliciting HbA1c reductions consistent with those previously reported for a patient population with much more recent onset of type 2 diabetes and normal renal function, and had a hypoglycemic profile comparable with placebo. Accordingly, vildagliptin is a suitable treatment option for patients with advanced type 2 diabetes and impaired renal function who require insulin therapy and present a serious therapeutic challenge in clinical practice. PMID:23378769

  5. Biochemical studies on gestational diabetes mellitus and impaired glucose tolerance in Sudanese pregnant women

    International Nuclear Information System (INIS)

    Shalayel, Mohammed Helmy Faris

    1998-01-01

    To detect the effect of some maternal risk factors such as age, parity, previous heavy babies and family history of diabetes, in glucose tolerance impairment and to stand on the state of insulin resistance which occurs in pregnancy and the possible role of cortisol, human placental lactogen and prolactin in augmentation of this state of insulin resistance as well as to show the effect of glucose tolerance deterioration on lipid metabolism, a study was carried out on Sudanese pregnant women. The study included thirty gestational diabetes mellitus (GDM) pregnant women, thirty impaired glucose tolerance (IGT) and thirty women with normal glucose tolerance as a control group. The GDM, IGT and the control group were screened from about 2000 Sudanese pregnant women in the different gestational weeks. The GDM and IGT women were all discovered in the third trimester of pregnancy, they found to be significantly older than the control group. The IGT group was found to have a first degree family history of diabetes incidence significantly more than that of the control group while the GDM group has significantly much higher results when compared with the normal control group. The incidence of previous heavy babies was significantly higher in the IGT group when compared with the control while that of GDM was significantly much higher. The GDM group was found to have significantly higher mean levels of fasting blood plasma glucose sugar than that of the IGT and the control groups. It was found that the serum cholestrol mean level and the serum triglycerides mean level of the IGT and that of the GDM were significantly higher than that of the control group. Also, there were no significant differences among serum fasting insulin mean levels of the three studied groups. Results of serum anti-insulin antibodies of the three studied groups were significantly different. Results of serum cortisol of the control group in the first, second and third trimesters revealed that cortisol

  6. Hypoglycaemia and QT interval prolongation in type 1 diabetes - bridging the gap between clamp studies and spontaneous episodes

    DEFF Research Database (Denmark)

    Christensen, Toke F.; Cichosz, Simon Lebech; Tarnow, Lise

    2014-01-01

    AIMS: We propose a study design with controlled hypoglycaemia induced by subcutaneous injection of insulin and matched control episodes to bridge the gap between clamp studies and studies of spontaneous hypoglycaemia. The observed prolongation of the heart rate corrected QT interval (QTc) during...... hypoglycaemia varies greatly between studies. METHODS: We studied ten adults with type 1 diabetes (age 41±15years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4weeks. QT...

  7. The dynamics of the microcirculation in the subcutaneous adipose tissue is impaired in the postprandial state in type 2 diabetes

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, Jens

    2011-01-01

    that the postprandial adipose tissue blood flow (ATBF) increase is accompanied by capillary recruitment in healthy subjects. The aim of the present study was to investigate whether the postprandial capillary recruitment in adipose tissue is affected in type 2 diabetes mellitus. Eight type 2 diabetic overweight male....... No significant changes were found in the ATBF or in capillary recruitment in the type 2 diabetic subjects. There was no significant blood flow or microvascular blood volume changes in forearm skeletal muscle in either of the groups. CONCLUSION: After an oral glucose load, the abdominal ATBF and microvascular...... blood volume changes in abdominal subcutaneous adipose tissue are impaired in overweight type 2 diabetic subjects compared to weight-matched healthy subjects....

  8. Insulin Resistance and Impaired Pancreatic β-Cell Function in Adult Offspring of Women With Diabetes in Pregnancy

    DEFF Research Database (Denmark)

    Kelstrup, Louise; Damm, Peter; Mathiesen, Elisabeth R

    2013-01-01

    Context:Offspring of women with diabetes during pregnancy have increased risk of glucose intolerance in adulthood, but the underlying mechanisms are unknown.Objective:We aimed to investigate effects of intrauterine hyperglycemia on insulin secretion and - action in adult offspring of mothers...... a standard oral glucose tolerance test (120 minutes, 75 gram glucose). Pancreatic beta-cell function taking the prevailing insulin sensitivity into account was estimated by disposition indices.Results:Both groups of offspring exposed during pregnancy to either maternal gestational diabetes or type 1 diabetes.......005).Conclusion:Reduced insulin sensitivity as well as impaired pancreatic beta cell function may contribute to the increased risk of glucose intolerance among adult offspring born to women with diabetes during pregnancy....

  9. Impairment of Colour Vision in Diabetes with No Retinopathy: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SNDREAMS- II, Report 3.

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    Laxmi Gella

    Full Text Available To assess impairment of colour vision in type 2 diabetics with no diabetic retinopathy and elucidate associated risk factors in a population-based cross-sectional study.This is part of Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular-genetics Study (SN-DREAMS II which was conducted between 2007-2010. FM 100 hue-test was performed in 253 subjects with no clinical evidence of diabetic retinopathy. All subjects underwent detailed ophthalmic evaluation including cataract grading using LOCS III and 45° 4-field stereoscopic fundus photography. Various ocular and systemic risk factors for impairment of colour vision (ICV were assessed in subjects with diabetes but no retinopathy. P value of < 0.05 was considered statistically significant.The mean age of the study sample was 57.08 ± 9.21 (range: 44-86 years. Gender adjusted prevalence of ICV among subjects with diabetes with no retinopathy was 39.5% (CI: 33.5-45.5. The mean total error score in the study sample was 197.77 ± 100 (range: 19-583. The risk factors for ICV in the study were women OR: 1.79 (1.00-3.18, increased resting heart rate OR: 1.04 (1.01-1.07 and increased intraocular pressure OR: 1.12 (1.00-1.24. Significant protective factor was serum high-density lipoprotein OR: 0.96 (0.93-0.99.Acquired ICV is an early indicator of neurodegenerative changes in the retina. ICV found in diabetic subjects without retinopathy may be of non-vascular etiology.

  10. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat.

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    Visser, J T J; Lammers, K; Hoogendijk, A; Boer, M W; Brugman, S; Beijer-Liefers, S; Zandvoort, A; Harmsen, H; Welling, G; Stellaard, F; Bos, N A; Fasano, A; Rozing, J

    2010-12-01

    Impaired intestinal barrier function is observed in type 1 diabetes patients and animal models of the disease. Exposure to diabetogenic antigens from the intestinal milieu due to a compromised intestinal barrier is considered essential for induction of the autoimmune process leading to type 1 diabetes. Since a hydrolysed casein (HC) diet prevents autoimmune diabetes onset in diabetes-prone (DP)-BioBreeding (BB) rats, we studied the role of the HC diet on intestinal barrier function and, therefore, prevention of autoimmune diabetes onset in this animal model. DP-BB rats were fed the HC diet from weaning onwards and monitored for autoimmune diabetes development. Intestinal permeability was assessed in vivo by lactulose-mannitol test and ex vivo by measuring transepithelial electrical resistance (TEER). Levels of serum zonulin, a physiological tight junction modulator, were measured by ELISA. Ileal mRNA expression of Myo9b, Cldn1, Cldn2 and Ocln (which encode the tight junction-related proteins myosin IXb, claudin-1, claudin-2 and occludin) and Il-10, Tgf-ß (also known as Il10 and Tgfb, respectively, which encode regulatory cytokines) was analysed by quantitative PCR. The HC diet reduced autoimmune diabetes by 50% in DP-BB rats. In DP-BB rats, prediabetic gut permeability negatively correlated with the moment of autoimmune diabetes onset. The improved intestinal barrier function that was induced by HC diet in DP-BB rats was visualised by decreasing lactulose:mannitol ratio, decreasing serum zonulin levels and increasing ileal TEER. The HC diet modified ileal mRNA expression of Myo9b, and Cldn1 and Cldn2, but left Ocln expression unaltered. Improved intestinal barrier function might be an important intermediate in the prevention of autoimmune diabetes by the HC diet in DP-BB rats. Effects on tight junctions, ileal cytokines and zonulin production might be important mechanisms for this effect.

  11. Association of Chronic Kidney Disease and Cerebral Small Vessel Disease with Cognitive Impairment in Elderly Patients with Type 2 Diabetes

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    Toshitaka Umemura

    2013-07-01

    Full Text Available Background/Aims: In recent years, the relationship between chronic kidney disease (CKD and cognitive impairment has been attracting attention. Cerebral small vessel disease (SVD is also associated with an increased risk of cognitive impairment. However, it is still unknown whether CKD markers are associated with cognitive impairment independently of SVD in elderly diabetic patients. Methods: Seventy-nine type 2 diabetic patients (mean age, 76.0 years were enrolled in the present study. CKD was defined as the presence of albuminuria and/or a low estimated glomerular filtration rate (eGFR 2. SVD was evaluated by the presence and severity of silent brain infarcts (SBIs and white matter lesions (WMLs on brain magnetic resonance imaging. Neuropsychological tests were assessed using four validated cognitive instruments. Results: In multiple linear regression analyses, albuminuria was associated with worse modified Stroop Color Word scores (β = 0.284, p = 0.017 and low eGFR was associated with reduced Digit Symbol Substitution scores (β = -0.224, p = 0.026 after adjustment for age, sex, education years, diabetes duration, hypertension, multiple SBIs, and advanced WMLs. In contrast, there were no significant associations between CKD markers and Mini-Mental State Examination or Word Recall scores. Conclusion: Our findings suggest that albuminuria and low eGFR are associated with frontal lobe dysfunction independently of SVD in elderly type 2 diabetic patients.

  12. Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality.

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    Baccetti, Baccio; La Marca, Antonio; Piomboni, Paola; Capitani, Serena; Bruni, Emanuele; Petraglia, Felice; De Leo, Vincenzo

    2002-10-01

    The objective of the study was to investigate the hypothalamo-pituitary-testicular axis and sperm structure at the transmission electron microscope (TEM) level in men affected by insulin-dependent diabetes. Twenty-two diabetic men and 24 controls were recruited. GnRH (100 micro g) was administered and FSH- and LH-induced secretion was evaluated. Semen samples were collected and sperm concentration and motility were determined using a Makler chamber. Ejaculated sperm were fixed and observed with a TEM. The response of gonadotrophins to GnRH was significantly lower in diabetics than in control men. Sperm motility was also significantly lower. At the electron microscope level, sperm from diabetics exhibited a higher percentage of immaturity- and apoptosis-related defects than sperm from controls. The reduced response of gonadotrophins to GnRH in diabetic men may indicate a decreased acute releasable pool of pituitary gonadotrophins. The results of TEM examination showed that sperm from men with diabetes presented severe structural defects in comparison with sperm from controls. It is possible that the reproductive impairment recognized in men with diabetes could be the result of interference by the disease on the hypothalamo-pituitary-testicular axis at multiple levels, as indicated by the reduced gonadotrophin response to appropriate stimuli and by the abnormal ultrastructure of ejaculated sperm. The defective spermatogenesis may be the consequence of a direct testicular effect of the disease.

  13. Identification of Risk Factors Affecting Impaired Fasting Glucose and Diabetes in Adult Patients from Northeast China

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    Yutian Yin

    2015-10-01

    Full Text Available Background: Besides genetic factors, the occurrence of diabetes is influenced by lifestyles and environmental factors as well as trace elements in diet materials. Subjects with impaired fasting glucose (IFG have an increased risk of developing diabetes mellitus (DM. This study aimed to explore risk factors affecting IFG and diabetes in patients from Northeast China. Methods: A population-based, cross-sectional survey of chronic diseases and related risk factors was conducted in Jilin Province of Northeast China. All adult residents, aged 18–79, were invited to participate in this survey using the method of multistage stratified random cluster sampling. One hundred thirty-four patients with IFG or DM and 391 healthy control subjects were recruited. We compared demographic factors, body size measurements, healthy-related behaviors, and hair metallic element contents between IFG/diabetes patients and healthy individuals. Results: IFG/diabetes patients had a greater weight, waist, hip, and body mass index (BMI than control subjects. Significant differences in the content of zinc (Zn, potassium (K, copper (Ca, and sodium (Na as well as Cu/Zn ratios between IFG or DM patients and control subjects (p < 0.05 were also observed. Hair Cu, selenium (Se, and Na contents were positively correlated with blood glucose levels (Cu: rs = 0.135, p = 0.002; Se: rs = 0.110, p = 0.012; Na: rs = 0.091, p = 0.038. Polytomous logistic regression adjusting for age, sex, family history of diabetes and BMI, showed that subjects with high BMI were more likely to develop IFG and DM (IFG: OR = 1.15, OR 95% CI = 1.02–1.29; DM: OR = 1.15, OR 95% CI = 1.01–1.33. Moreover, rarely or never eating fruits was a risk factor for DM (OR = 5.46, OR 95% CI = 1.87–15.98 but not for IFG (OR = 1.70, OR 95% CI = 0.72–4.02. Subjects with abdominal obesity or DM history were more susceptible to DM (abdominal obesity: OR = 2.99, OR 95% CI = 1.07–8.37; DM history: OR = 2.69, OR 95

  14. Ferulic acid attenuates diabetes-induced cognitive impairment in rats via regulation of PTP1B and insulin signaling pathway.

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    Wang, Hao; Sun, Xiaoxu; Zhang, Ning; Ji, Zhouye; Ma, Zhanqiang; Fu, Qiang; Qu, Rong; Ma, Shiping

    2017-12-01

    Cognitive impairment has been recognized as a typical characteristic of neurodegenerative disease in diabetes mellitus (DM) and this cognitive dysfunction may be a risk factor for Alzheimer's disease (AD). Ferulic acid, a phenolic compound commonly found in a range of plants, has emerged various properties including anti-inflammatory and neuroprotective effects. In the present study, the protective activities and relevant mechanisms of ferulic acid were evaluated in diabetic rats with cognitive deficits, which were induced by a high-glucose-fat (HGF) diet and low dose of streptozotocin (STZ). It was observed that ferulic acid significantly increased body weight and decreased blood glucose levels. Meanwhile, ferulic acid could markedly ameliorate spatial memory of diabetic rats in Morris water maze (MWM) and decrease AD-like pathologic changes (Aβ deposition and Tau phosphorylation) in the hippocampus, which might be correlated with the inhibition of inflammatory cytokines release and reduction of protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, the levels of brain insulin signal molecules p-IRS, p-Akt and p-GSK3β were also investigated. We found that ferulic acid administration restored the alterations in insulin signaling. In conclusion, ferulic acid exhibited beneficial effects on diabetes-induced cognition lesions, which was involved in the regulation of PTP1B and insulin signaling pathway. We suppose that PTP1B inhibition may represent a promising approach to correct abnormal signaling linked to diabetes-induced cognitive impairment. Copyright © 2017. Published by Elsevier Inc.

  15. Impaired oxidation of carbon-labeled galactose by alcoholic or diabetic liver in vivo

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    Shreeve, W.W.

    1987-01-01

    Because of the organ and enzyme specificity of the metabolism of galactose, evaluation of various kinds of liver disease can be done by measuring the formation of labeled breath CO 2 from carbon-labeld galactose in vivo. As shown earlier with uniformly 14 C- or 13 C-labeld galactose, a further study of alcoholic cirrhotic patients and controls with cheaper 1- 14 C-galactose indicates a superior discriminatory value of this test compared with common liver functions tests. The oxidation test is easier to perform and more acceptable to patients than the standard galactose tolerance blood test. Output of 14 CO 2 showed slight correlations with serum albumin and 99m Tc-sulfur colloid scan grade, but not with other function tests (SGOT, alkaline phosphatase, bilirubin). Comparison with five-year clinical outcome (two groups: with or without known liver-related death) in 29 of 43 total cirrhotic patients (U- 14 C or 1- 14 C-galactose) showed a low (75% probability) significance of prognosis for the galactose oxidation test, but none for any of the other tests. A two-part test of oxidation of 14 C-galactose (with and without an acute dose of ethanol) in 19 possibly or likely alcoholic (but non-cirrhotic) persons indicated, by correlation with other liver function tests and drinking history, some possibly enhanced sensitivity of the two-part versus the single test for recognizing early liver damage. A preliminary study of the single galactose oxidation test in 7 patients with Type II diabetes suggests moderate impairment of oxidation, which might be applied to evaluate the hepatic disorder in diabetes. (orig.) [de

  16. Combined prevalence of impaired glucose level or diabetes and its correlates in Lusaka urban district, Zambia: a population based survey

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    Nsakashalo-Senkwe Mutale

    2011-01-01

    Full Text Available Abstract Background Developing countries are undergoing an epidemiological transition, from Communicable or Infectious to 'Non-Communicable' diseases (NCDs, such that cardiovascular disease, chronic respiratory diseases, cancer, and diabetes were responsible for 60% of all deaths globally in 2005, with more than 75% of these deaths occurring in developing countries. A survey was conducted to determine among other objectives the prevalence of diabetes and its association with physical fitness and biological factors. Methods A cross sectional study utilizing a modified World Health Organization's STEPwise approach to surveillance of NCDs was conducted in Lusaka district, Zambia. A multi-stage cluster sampling technique was used to select study participants of age 25 years or older. All eligible members of a household that was selected were invited to participate in the study. Unadjusted odds ratios (OR, and adjusted odds ratios (AOR together with their 95% Confidence Intervals (CI were obtained using Complex samples logistic regression Results A total of 1928 individuals participated in the survey, of which 33.0% were males. About half of the participants were of age 25-34 years (53.2%, and about a third of the respondents had attained secondary level of education (35.8%. The combined prevalence for impaired glucose level or diabetes was 4.0%. Age and mild hypertension were significantly associated with impaired levels of glucose or diabetes. Compared to participants in the age group 25-34 years, older participants were more likely to have impaired glucose level or diabetes (AOR = 2.49 (95%CI [1.35, 2.92] for 35-44 years age group, and AOR = 3.80 (95%CI [2.00, 7.23] for 45 + years age group. Mild hypertension was associated with impaired glucose level or diabetes (AOR = 2.57 (95%CI [1.44, 4.57]. Conclusions The prevalence of diabetes in Lusaka district has not reached an alarming level and it is now that interventions targeting the younger age

  17. Relative contributions of energy expenditure on physical activity, body composition and weight gain to the evolution of impaired glucose tolerance to Frank diabetes. Highlights and achievements

    International Nuclear Information System (INIS)

    Forrester, T.

    2002-01-01

    There is a gradient of diabetes prevalence among populations of the African Diaspora. HYPOTHESIS: The risk of diabetes in transitional populations of the African diaspora is directly related to the rate of anthropornetric change and physical activity. AIMS: - To determine whether risk of incident diabetes and impaired glucose tolerance is related to physical activity in two populations of the African Diaspora with widely different levels of obesity; - To determine whether risk of incident diabetes and impaired glucose tolerance is related to rate of rise in body weight and change in body composition

  18. Gaps and barriers in the control of blood glucose in people with type 2 diabetes.

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    Blonde, Lawrence; Aschner, Pablo; Bailey, Clifford; Ji, Linong; Leiter, Lawrence A; Matthaei, Stephan

    2017-05-01

    Glycaemic control is suboptimal in a large proportion of people with type 2 diabetes who are consequently at an increased and avoidable risk of potentially severe complications. We sought to explore attitudes and practices among healthcare professionals that may contribute to suboptimal glycaemic control through a review of recent relevant publications in the scientific literature. An electronic search of the PubMed database was performed to identify relevant publications from January 2011 to July 2015. The electronic search was complemented by a manual search of abstracts from key diabetes conferences in 2014/2015 available online. Recently published data indicate that glycaemic control is suboptimal in a substantial proportion (typically 40%-60%) of people with diabetes. This is the case across geographic regions and in both low- and higher-income countries. Therapeutic inertia appears to be an important contributor to poor glycaemic control in up to half of people with type 2 diabetes. In particular, prescribers are often willing to tolerate extended periods of 'mild' hyperglycaemia as well as having low expectations for their patients. There are often delays of 3 years or longer in initiating or intensifying glucose-lowering therapy when needed. Many people with type 2 diabetes are failed by current management, with approximately half not achieving or maintaining appropriate target blood glucose levels, leaving these patients at increased and avoidable risk of serious complications. Review criteria: The methodology of this review article is detailed in the 'Methods' section.

  19. Prevalence of diabetes and impaired fasting glucose in Peru: report from PERUDIAB, a national urban population-based longitudinal study.

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    Seclen, Segundo N; Rosas, Moises E; Arias, Arturo J; Huayta, Ernesto; Medina, Cecilia A

    2015-01-01

    We aimed to estimate the prevalences of diabetes and impaired fasting glucose (IFG) in a national sample in Peru and assess the relationships with selected sociodemographic variables. We estimated prevalence in PERUDIAB study participants, a nationwide, stratified urban and suburban population selected by random cluster sampling. Between 2010 and 2012, questionnaires were completed and blood tests obtained from 1677 adults ≥25 years of age. Known diabetes was defined as participants having been told so by a doctor or nurse and/or receiving insulin or oral antidiabetic agents. Newly diagnosed diabetes was defined as fasting plasma glucose ≥126 mg/dL determined during the study and without a previous diabetes diagnosis. IFG was defined as fasting plasma glucose of 100-125 mg/dL. The estimated national prevalence of diabetes was 7.0% (95% CI 5.3% to 8.7%) and it was 8.4% (95% CI 5.6% to 11.3%) in metropolitan Lima. No gender differences were detected. Known and newly diagnosed diabetes prevalences were estimated as 4.2% and 2.8%, respectively. A logistic regression response surface model showed a complex trend for an increased prevalence of diabetes in middle-aged individuals and in those with no formal education. Diabetes prevalence was higher in coastal (8.2%) than in highlands (4.5%; p=0.03), and jungle (3.5%; pdiabetes as an important public health problem, especially for middle-aged individuals and those with no formal education. 40% of the affected individuals were undiagnosed. The elevated prevalence of IFG shows that nearly a quarter of the adult population of Peru has an increased risk of diabetes.

  20. Cardiovascular disease risk factors in a Nigerian population with impaired fasting blood glucose level and diabetes mellitus.

    Science.gov (United States)

    Oguoma, Victor M; Nwose, Ezekiel U; Ulasi, Ifeoma I; Akintunde, Adeseye A; Chukwukelu, Ekene E; Bwititi, Phillip T; Richards, Ross S; Skinner, Timothy C

    2017-01-06

    Diabetes is a risk factor for cardiovascular diseases (CVDs) and there are reports of increasing prevalence of prediabetes in Nigeria. This study therefore characterised CVDs risk factors in subjects with impaired fasting glucose (IFG) and diabetes. Data from 4 population-based cross-sectional studies on 2447 apparently healthy individuals from 18 - 89 years were analysed. Anthropometric, blood pressure and biochemical parameters were collected and classified. Individuals with IFG (prediabetes) and diabetes were merged each for positive cases of dyslipidaemia, high blood pressure (HBP) or obesity. Optimal Discriminant and Hierarchical Optimal Classification Tree Analysis (HO-CTA) were employed. Overall prevalence of IFG and diabetes were 5.8% (CI: 4.9 - 6.7%) and 3.1% (CI: 2.4 - 3.8%), respectively. IFG co-morbidity with dyslipidaemia (5.0%; CI: 4.1 - 5.8%) was the highest followed by overweight/obese (3.1%; CI: 2.5 - 3.8%) and HBP (1.8%; CI: 1.3 - 2.4%). The predicted age of IFG or diabetes and their co-morbidity with other CVD risk factors were between 40 - 45 years. Elevated blood level of total cholesterol was the most predictive co-morbid risk factor among IFG and diabetes subjects. Hypertriglyceridaemia was an important risk factor among IFG-normocholesterolaemic-overweight/obese individuals. The higher prevalence of co-morbidity of CVD risk factors with IFG than in diabetes plus the similar age of co-morbidity between IFG and diabetes highlights the need for risk assessment models for prediabetes and education of individuals at risk about factors that mitigate development of diabetes and CVDs.

  1. A Complex Approach to Noninvasive Estimation of Microcirculatory Tissue Impairments in Feet of Patients with Diabetes Mellitus using Spectroscopy

    Science.gov (United States)

    Potapova, E. V.; Dremin, V. V.; Zherebtsov, E. A.; Makovik, I. N.; Zharkikh, E. V.; Dunaev, A. V.; Pilipenko, O. V.; Sidorov, V. V.; Krupatkin, A. I.

    2017-12-01

    The possibility of a complex approach for studying changes in the system of blood microcirculation and metabolic processes in the biotissue of lower extremities using optical noninvasive methods of laser doppler flowmetry (LDF), fluorescence spectroscopy, and diffuse reflectance spectroscopy in combination with different modes of heating tests has been assessed. Seventy-six patients with type 2 diabetes mellitus, with 14 patients having visible trophic foot impairments, and 48 healthy volunteers have been examined. The parameters of LDF signals and spectra of fluorescence intensity and diffuse reflectance for foot skin have been analyzed. Statistically significant differences in the recorded parameters between the groups under study have been found. It has been concluded that combined application of noninvasive methods of spectroscopy could be used for diagnostics of complications both upon the occurrence of preliminary symptoms of diabetes, when pathological changes are still reversible, and in the presence of impairments to prevent aggravation of the disease and select an adequate correction of the treatment.

  2. Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models.

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    Juan Jose Ramos-Rodriguez

    Full Text Available Type 2 diabetes (T2D is an important risk factor to suffer dementia, including Alzheimer's disease (AD, and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS morphological alterations in the db/db mice (leptin receptor KO mice, as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD, as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis.

  3. Plasma lipoprotein(a levels are associated with mild renal impairment in type 2 diabetics independent of albuminuria.

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    Jennie Lin

    Full Text Available CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.In the Penn Diabetes Heart Study (PDHS, a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852. Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point were performed.Mild GFR impairment (eGFR 60-90 mL/min/1.73 m², median urinary ACR 5.25 mg/g was associated with higher log-transformed Lp(a values (OR 1.17, p = 0.005 and with clinically atherogenic Lp(a levels above 30 mg/dL (OR 1.35, p = 0.013 even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17 as well as apoC-III (p = 0.067 in the fully adjusted model.Elevated Lp(a levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.

  4. Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

    Science.gov (United States)

    Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

    2012-10-01

    To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (pcognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. System of matrix metalloproteinases and cytokine secretion in type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension.

    Science.gov (United States)

    Kologrivova, I V; Suslova, T E; Koshel'skaya, O A; Vinnitskaya, I V; Trubacheva, O A

    2014-03-01

    The study included patients with type 2 diabetes mellitus and impaired carbohydrate tolerance associated with arterial hypertension, patients with arterial hypertension, and healthy volunteers. We evaluated the levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloproteinase type 1 (TIMP-1), glucose, insulin, C-peptide, glycated hemoglobin, and spontaneous and mitogen-activated cytokine secretion (IL-2, IL4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ). Patients with type 2 diabetes mellitus in combination with arterial hypertension exhibited maximum TIMP-1 levels and TIMP-1/MMP-2, TIMP-1/ MMP-9 ratios as well as enhanced secretion of TNF-α, IL-6, IL-17 and reduced secretion of IL-10 in comparison with healthy individuals. The observed shifts are probably determined the development of systemic hyperinsulinemia in patients suffering from type 2 diabetes mellitus coupled with arterial hypertension.

  6. Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle.

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    Matthew P Krause

    Full Text Available Systemic elevations in PAI-1 suppress the fibrinolytic pathway leading to poor collagen remodelling and delayed regeneration of tibialis anterior (TA muscles in type-1 diabetic Akita mice. However, how impaired collagen remodelling was specifically attenuating regeneration in Akita mice remained unknown. Furthermore, given intrinsic differences between muscle groups, it was unclear if the reparative responses between muscle groups were different.Here we reveal that diabetic Akita muscles display differential regenerative responses with the TA and gastrocnemius muscles exhibiting reduced regenerating myofiber area compared to wild-type mice, while soleus muscles displayed no difference between animal groups following injury. Collagen levels in TA and gastrocnemius, but not soleus, were significantly increased post-injury versus controls. At 5 days post-injury, when degenerating/necrotic regions were present in both animal groups, Akita TA and gastrocnemius muscles displayed reduced macrophage and satellite cell infiltration and poor myofiber formation. By 10 days post-injury, necrotic regions were absent in wild-type TA but persisted in Akita TA. In contrast, Akita soleus exhibited no impairment in any of these measures compared to wild-type soleus. In an effort to define how impaired collagen turnover was attenuating regeneration in Akita TA, a PAI-1 inhibitor (PAI-039 was orally administered to Akita mice following cardiotoxin injury. PAI-039 administration promoted macrophage and satellite cell infiltration into necrotic areas of the TA and gastrocnemius. Importantly, soleus muscles exhibit the highest inducible expression of MMP-9 following injury, providing a mechanism for normative collagen degradation and injury recovery in this muscle despite systemically elevated PAI-1.Our findings suggest the mechanism underlying how impaired collagen remodelling in type-1 diabetes results in delayed regeneration is an impairment in macrophage

  7. Periconception onset diabetes is associated with embryopathy and fetal growth retardation, reproductive tract hyperglycosylation and impaired immune adaptation to pregnancy.

    Science.gov (United States)

    Brown, Hannah M; Green, Ella S; Tan, Tiffany C Y; Gonzalez, Macarena B; Rumbold, Alice R; Hull, M Louise; Norman, Robert J; Packer, Nicolle H; Robertson, Sarah A; Thompson, Jeremy G

    2018-02-01

    Diabetes has been linked with impaired fertility but the underlying mechanisms are not well defined. Here we use a streptozotocin-induced diabetes mouse model to investigate the cellular and biochemical changes in conceptus and maternal tissues that accompany hyperglycaemia. We report that streptozotocin treatment before conception induces profound intra-cellular protein β-O-glycosylation (O-GlcNAc) in the oviduct and uterine epithelium, prominent in early pregnancy. Diabetic mice have impaired blastocyst development and reduced embryo implantation rates, and delayed mid-gestation growth and development. Peri-conception changes are accompanied by increased expression of pro-inflammatory cytokine Trail, and a trend towards increased Il1a, Tnf and Ifng in the uterus, and changes in local T-cell dynamics that skew the adaptive immune response to pregnancy, resulting in 60% fewer anti-inflammatory regulatory T-cells within the uterus-draining lymph nodes. Activation of the heat shock chaperones, a mechanism for stress deflection, was evident in the reproductive tract. Additionally, we show that the embryo exhibits elevated hyper-O-GlcNAcylation of both cytoplasmic and nuclear proteins, associated with activation of DNA damage (ɣH2AX) pathways. These results advance understanding of the impact of peri-conception diabetes, and provide a foundation for designing interventions to support healthy conception without propagation of disease legacy to offspring.

  8. Using Ice Cream for Diagnosis of Diabetes Mellitus and Impaired Glucose Tolerance: An Alternative to the Oral Glucose Tolerance Test.

    Science.gov (United States)

    Chanprasertpinyo, Wandee; Bhirommuang, Nattapimon; Surawattanawiset, Titiporn; Tangsermwong, Thanwarin; Phanachet, Pariya; Sriphrapradang, Chutintorn

    2017-12-01

    Oral glucose tolerance test (OGTT) is a sensitive and reliable test for diabetes mellitus and impaired glucose tolerance (IGT). However, poor patient tolerance of glucose solutions is common. We aim to compare the diagnostic value of an ice cream test with a standard OGTT. A total of 104 healthy adults were randomly assigned to either 75-g OGTT or ice cream, followed by a crossover to the other test. Most patients were females (71%). Mean age was 37 ± 12 years, and body mass index was 24.2 ± 3.9kg/m 2 . Diabetes mellitus and IGT, as diagnosed by 75-g OGTT, were 4.8% and 6.7%, respectively. The 2-hour plasma glucose levels were 110 ± 55.5mg/dL with 75-g glucose and 97.52 ± 40.7mg/dL with ice cream. The correlation coefficient of 2-hour plasma glucose for the 2 tests was 0.82 (95% CI: 0.75-0.87; P ice cream test would have missed 5.76% of those at high risk for diabetes mellitus (impaired fasting glucose and IGT) or diabetes. An ice cream test may serve as an alternative to a 75-g OGTT. Before applying this test in clinical practice, it needs to be validated in a larger population. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  9. Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia

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    Lu Guan-Yi

    2010-12-01

    Full Text Available Abstract Background The Daming capsule (DMC is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM. This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ-induced diabetic rats with hyperlipoidemia. Methods Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats, and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE or sodium nitroprusside (SNP and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP. Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM. The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. Results Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR in response to PE-induced hypertension (+ΔMABP (P P P A receptor expression. Conclusion The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

  10. Can Cardiovascular Epidemiology and Clinical Trials Close the Risk Management Gap Between Diabetes and Prediabetes?

    DEFF Research Database (Denmark)

    Perreault, Leigh; Færch, Kristine; Gregg, Edward W

    2017-01-01

    PURPOSE OF REVIEW: We reviewed published literature to determine the relationship between A1c and cardiovascular disease (CVD) and summarize the need and implications for CVD risk reduction with interventions, focusing in the prediabetic A1c range (... a continuous relationship between A1c and CVD-even below the current levels of A1c-defined prediabetes and after adjustment for known risk factors for CVD. Clinical trials have demonstrated a reduction in CV morbidity and/or mortality when interventions are invoked in the prediabetic A1c range. Guidelines...... advocating CV risk factor management in prediabetes have not been widely adopted, subsequently leading to comparable coronary heart disease risk between people with prediabetes (HR = 1.9, 95% CI 1.7-2.1 vs normoglycemia) and diabetes itself (HR=2.0, 95% CI 1.8-2.2 vs no diabetes). This review highlights...

  11. Impaired insulin-stimulated nonoxidative glucose metabolism in glucose-tolerant women with previous gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P; Vestergaard, H; Kühl, Carl Erik

    1996-01-01

    Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes.......Our purpose was to investigate insulin sensitivity and insulin secretion in women with previous gestational diabetes....

  12. Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans.

    Directory of Open Access Journals (Sweden)

    Chen Liu

    Full Text Available Recent genome-wide association studies have identified a number of common variants associated with fasting glucose homeostasis and type 2 diabetes in populations of European origin. This is a replication study to examine whether such associations are also observed in Chinese Hans.We genotyped nine variants in or near MADD, ADRA2A, CRY2, GLIS3, PROX1, FADS1, C2CD4B, IGF1 and IRS1 in a population-based cohort including 3,210 unrelated Chinese Hans from Beijing and Shanghai.We confirmed the associations of GLIS3-rs7034200 with fasting glucose (beta = 0.07 mmol/l, P = 0.03, beta cell function (HOMA-B (beta = -3.03%, P = 0.009, and type 2 diabetes (OR [95%CI]  = 1.27 [1.09-1.49], P = 0.003 after adjustment for age, sex, region and BMI. The association for type 2 diabetes remained significant after adjusting for other diabetes related risk factors including family history of diabetes, lipid profile, medication information, hypertension and life style factors, while further adjustment for HOMA-B abolished the association. The A-allele of CRY2-rs11605924 was moderately associated with increased risk of combined IFG/type 2 diabetes (OR [95%CI]  = 1.15[1.01-1.30], P = 0.04. SNPs in or near MADD, ADRA2A, PROX1, FADS1, C2CD4B, IGF1, and IRS1 did not exhibit significant associations with type 2 diabetes or related glycemic traits (P≥0.10.In conclusion, our results indicate the associations of GLIS3 locus with type 2 diabetes and impaired fasting glucose in Chinese Hans, partially mediated through impaired beta-cell function. In addition, we also found modest evidence for the association of CRY2-rs11605924 with combined IFG/type 2 diabetes.

  13. Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood.

    Science.gov (United States)

    Hagman, E; Danielsson, P; Brandt, L; Ekbom, A; Marcus, C

    2016-08-22

    In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM. In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry - BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l(-1)) and WHO (6.1 mmol l(-1)). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l(-1)). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry. The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52-46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87-7.45) compared with those who had fasting glucose levels fasting glucose level of 5.6-6.0 mmol l(-1), that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84-3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50-6.52). More severe degree of obesity also increased the future T2DM risk. IFG according to WHO and elevated HbA1c (39-48 mmol l(-1)), but not the additional fasting glucose interval added by ADA (5.6-6.0 mmol l(-1)), can be considered as prediabetes in the obese pediatric population in Sweden.

  14. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and woman. The Hoorn Study.

    NARCIS (Netherlands)

    Snijder, M.B.; Heine, R.J.; Seidell, J.C.; Bouter, L.M.; Stehouwer, C.D.A.; Nijpels, M.G.A.A.M.; Funahashi, T.; Matsuzawa, Y.; Shimonura, I.; Dekker, J.M.

    2006-01-01

    OBJECTIVE - Adiponectin is an adipose tissue- derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose

  15. Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women : the hoorn study

    NARCIS (Netherlands)

    Snijder, Marieke B; Heine, Robert J; Seidell, Jacob C; Bouter, Lex M; Stehouwer, Coen D A; Nijpels, Giel; Funahashi, Tohru; Matsuzawa, Yuji; Shimomura, Iichiro; Dekker, Jacqueline M

    2006-01-01

    OBJECTIVE: Adiponectin is an adipose tissue-derived protein. Low levels are associated with obesity, insulin resistance, and type 2 diabetes. Our objective was to investigate the prospective association between adiponectin levels and the 6.4-year risk of type 2 diabetes and of impaired glucose

  16. Neurotrophin p75 receptor (p75NTR) promotes endothelial cell apoptosis and inhibits angiogenesis: implications for diabetes-induced impaired neovascularization in ischemic limb muscles

    NARCIS (Netherlands)

    Caporali, Andrea; Pani, Elisabetta; Horrevoets, Anton J. G.; Kraenkel, Nicolle; Oikawa, Atsuhiko; Sala-Newby, Graciela B.; Meloni, Marco; Cristofaro, Brunella; Graiani, Gallia; Leroyer, Aurelie S.; Boulanger, Chantal M.; Spinetti, Gaia; Yoon, Sung Ok; Madeddu, Paolo; Emanueli, Costanza

    2008-01-01

    Diabetes impairs endothelial function and reparative neovascularization. The p75 receptor of neurotrophins (p75(NTR)), which is scarcely present in healthy endothelial cells (ECs), becomes strongly expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. Here, we

  17. Impaired vascular function during short-term poor glycaemic control in Type 1 diabetic patients

    DEFF Research Database (Denmark)

    Sørensen, V.R.; Mathiassen, E.R.; Clausen, P.

    2005-01-01

    AIM: To study the effects of short-term poor glycaemic control on vascular function in Type 1 diabetic patients. METHODS: Ten Type 1 diabetic patients, with diabetes duration of less than 10 years and normal urinary albumin excretion and ophthalmoscopy, were studied. All patients were examined af...

  18. The treatment of type 2 diabetes in the presence of renal impairment: what we should know about newer therapies

    Directory of Open Access Journals (Sweden)

    Davies M

    2016-06-01

    Full Text Available Melanie Davies,1,2 Sudesna Chatterjee,1,2 Kamlesh Khunti1,2 1Diabetes Research Centre, University of Leicester, 2Leicester Diabetes Centre, University Hospitals of Leicester NHS Trust, Leicester, UK Abstract: Worldwide, an estimated 200 million people have chronic kidney disease (CKD, the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2–5 and without dose adjustment; there are contraindications and dose adjustments required for the remaining standard therapies. Newer therapies, particularly dipeptidyl peptidase-IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors, are increasingly being used in the treatment of type 2 diabetes; however, a major consideration is whether these newer therapies can also be used safely and effectively across the spectrum of renal impairment. Notably, reductions in albuminuria, a marker of CKD, are observed with many of the drug classes. Dipeptidyl peptidase-IV inhibitors can be used in all stages of renal impairment, with appropriate dose reduction, with the exception of linagliptin, which can be used without dose adjustment. No dose adjustment is required for liraglutide, albiglutide, and dulaglutide in CKD stages 2 and 3, although all glucagon-like peptide-1 receptor agonists are currently contraindicated in stages 4 and 5 CKD. At stage 3 CKD or greater, the sodium

  19. Impaired Leptomeningeal Collateral Flow Contributes to the Poor Outcome following Experimental Stroke in the Type 2 Diabetic Mice

    Science.gov (United States)

    Akamatsu, Yosuke; Nishijima, Yasuo; Lee, Chih Cheng; Yang, Shih Yen; Shi, Lei; An, Lin; Wang, Ruikang K.; Tominaga, Teiji

    2015-01-01

    Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects. PMID:25740515

  20. Cognitive impairment in diabetes mellitus and hypertension, a possibility of correction

    Directory of Open Access Journals (Sweden)

    I. Ch. Khairullin

    2016-01-01

    Full Text Available Objective: to evaluate cognitive functions in patients with type 2 diabetes mellitus (DM2 and hypertension and the efficacy of Ginkgo biloba extract Egb 761®.Patients and methods. 120 patients with DM2 and 50 hypertensive patients with no complications or a history of stroke and/or myocardial infarction, without active complaints of hypomnesia and other cognitive functions were examined. The exclusion criteria were prior stroke and/or myocardial infarction; clinically significant diseases of the peripheral arteries and major arteries of the head; DM2 decompensation; glomerular filtration rate <60 ml/min; proliferative retinopathy; and other endocrine diseases. The investigators used the following methods for the evaluation of cognitive functions: the Mini-Mental State Examination, the Montreal Cognitive Assessment, and the hand- eye coordination test (Parts A and B.Results and discussion. 85% of the patients with DM2 were found to have cognitive impairments (CI: disorders of attention, short-term memory, and thinking speed. Out of them, 82.5% had moderate CI and 2.5% had dementia. 30% of the hypertensive patients were diagnosed as having moderate CIs and 10% had dementia. At the same time, the degree of CI was higher in the patients with MD2 than in those with hypertension. The use of Egb 761® 240 mg/day for 3 months had a statistically significant positive impact on cognitive functions (improvements in short-term memory, concentration, and thinking speed and everyday activity.Conclusion. The authors consider that CIs are the first sign of encephalopathy in DM2. It is also noted that DM2 has a more pronounced impact on cognitive functions than hypertension. Egb 761® can be used as an effective drug to treat CI in these diseases.

  1. The molecular signature of impaired diabetic wound healing identifies serpinB3 as a healing biomarker.

    Science.gov (United States)

    Fadini, Gian Paolo; Albiero, Mattia; Millioni, Renato; Poncina, Nicol; Rigato, Mauro; Scotton, Rachele; Boscari, Federico; Brocco, Enrico; Arrigoni, Giorgio; Villano, Gianmarco; Turato, Cristian; Biasiolo, Alessandra; Pontisso, Patrizia; Avogaro, Angelo

    2014-09-01

    Chronic foot ulceration is a severe complication of diabetes, driving morbidity and mortality. The mechanisms underlying delaying wound healing in diabetes are incompletely understood and tools to identify such pathways are eagerly awaited. Wound biopsies were obtained from 75 patients with diabetic foot ulcers. Matched subgroups of rapidly healing (RH, n = 17) and non-healing (NH, n = 11) patients were selected. Proteomic analysis was performed by labelling with isobaric tag for relative and absolute quantification and mass spectrometry. Differentially expressed proteins were analysed in NH vs RH for identification of pathogenic pathways. Individual sample gene/protein validation and in vivo validation of candidate pathways in mouse models were carried out. Pathway analyses were conducted on 92/286 proteins that were differentially expressed in NH vs RH. The following pathways were enriched in NH vs RH patients: apoptosis, protease inhibitors, epithelial differentiation, serine endopeptidase activity, coagulation and regulation of defence response. SerpinB3 was strongly upregulated in RH vs NH wounds, validated as protein and mRNA in individual samples. To test the relevance of serpinB3 in vivo, we used a transgenic mouse model with α1-antitrypsin promoter-driven overexpression of human SERPINB3. In this model, wound healing was unaffected by SERPINB3 overexpression in non-diabetic or diabetic mice with or without hindlimb ischaemia. In an independent validation cohort of 47 patients, high serpinB3 protein content was confirmed as a biomarker of healing improvement. We provide a benchmark for the unbiased discovery of novel molecular targets and biomarkers of impaired diabetic wound healing. High serpinB3 protein content was found to be a biomarker of successful healing in diabetic patients.

  2. Oral administration of soybean peptide Vglycin normalizes fasting glucose and restores impaired pancreatic function in Type 2 diabetic Wistar rats.

    Science.gov (United States)

    Jiang, Hua; Feng, Jueping; Du, Zhongxia; Zhen, Hui; Lin, Mei; Jia, Shaohui; Li, Tao; Huang, Xinyuan; Ostenson, Claes-Goran; Chen, Zhengwang

    2014-09-01

    Vglycin, a natural 37-residue polypeptide isolated from pea seeds in which six half-cysteine residues are embedded in three pairs of disulfide bonds, is resistant to digestive enzymes and has antidiabetic potential. To investigate the pharmacological activity of Vglycin in vivo and to examine the mechanisms involved, the therapeutic effect of Vglycin in diabetic rats was examined. Diabetes was induced in Wistar rats by high-fat diet and multiple streptozotocin intraperitoneal injections. Diabetic rats were treated daily with Vglycin for 4 weeks. Body weight, food intake, fasting plasma glucose and insulin levels were assayed weekly. Glucose and insulin tolerance tests were conducted on Day 29. Subsequently, levels of p-Akt in the liver and pancreas and cleaved PARP, Pdx-1 and insulin in the pancreas were detected by immunoblotting. The morphology of the pancreas and the insulin expression in the pancreas were analyzed by hematoxylin-eosin staining and immunohistochemistry, respectively. Furthermore, human liver-derived cell lines were used to explore the in vitro effects of Vglycin on insulin sensitivity and glucose uptake. Chronic treatment with Vglycin normalized fasting glucose levels in diabetic rats. The improvement in glucose homeostasis and the increased insulin sensitivity mediated by restored insulin signaling likely contributed to decreased food intake and reduced body weight. Vglycin protected pancreatic cells from damage by streptozotocin. Although insulin synthesis and secretion in impaired β-cell were not significantly elevated, islets morphology was improved in the Vglycin-treated groups. These results suggest that Vglycin could be useful in Type 2 diabetes for restoring impaired insulin signaling, glucose tolerance and pancreatic function. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

    Directory of Open Access Journals (Sweden)

    Lukashevich V

    2013-01-01

    Full Text Available Valentina Lukashevich,1 Anja Schweizer,2 James E Foley,1 Sheila Dickinson,2 Per-Henrik Groop,3 Wolfgang Kothny11Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Novartis Pharma AG, Basel, Switzerland; 3Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Finland, and Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, AustraliaBackground: The purpose of this study was to evaluate the efficacy of vildagliptin 50 mg once daily in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2 and longstanding type 2 diabetes not adequately controlled with insulin therapy, which is a difficult-to-treat population, with limited therapeutic options and a high susceptibility to hypoglycemia.Methods: This was a post hoc subanalysis of data obtained during a previously described randomized, double-blind, parallel-group, 24-week study comparing the efficacy and safety of vildagliptin 50 mg once daily versus placebo in patients with type 2 diabetes and moderate or severe renal impairment. The present data derive from 178 patients with severe renal impairment (baseline estimated glomerular filtration rate approximately 21 mL/min/1.73 m2, 100 randomized to vildagliptin, 78 randomized to placebo, all of whom were receiving insulin therapy (alone or in combination with an oral antidiabetic agent for longstanding type 2 diabetes (mean approximately 19 years.Results: With vildagliptin in combination with insulin, the adjusted mean change (AMΔ in HbA1c from baseline (7.7% ± 0.1% was -0.9% ± 0.4% and the between-treatment difference (vildagliptin – placebo was -0.6% ± 0.2% (P < 0.001. The percentage of patients achieving endpoint HbA1c < 7.0% was significantly higher with vildagliptin than placebo (45.2% versus 22.8%, P = 0.008. When added to insulin, vildagliptin and placebo had

  4. Protein Kinase-C Beta Contributes to Impaired Endothelial Insulin Signaling in Humans with Diabetes Mellitus

    Science.gov (United States)

    Tabit, Corey E; Shenouda, Sherene M; Holbrook, Monica; Fetterman, Jessica L; Kiani, Soroosh; Frame, Alissa A; Kluge, Matthew A; Held, Aaron; Dohadwala, Mustali; Gokce, Noyan; Farb, Melissa; Rosenzweig, James; Ruderman, Neil; Vita, Joseph A; Hamburg, Naomi M

    2013-01-01

    Background Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of endothelial insulin signaling through the activity of protein kinase C-β (PKCβ) and nuclear factor κB (NFκB) reduces nitric oxide availability. We sought to establish whether similar mechanisms operate in the endothelium in human diabetes mellitus. Methods and Results We measured protein expression and insulin response in freshly isolated endothelial cells from patients with Type 2 diabetes mellitus (n=40) and non-diabetic controls (n=36). Unexpectedly, we observed 1.7-fold higher basal endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 in patients with diabetes (P=0.007) without a difference in total eNOS expression. Insulin stimulation increased eNOS phosphorylation in non-diabetic subjects but not in diabetic patients (P=0.003) consistent with endothelial insulin resistance. Nitrotyrosine levels were higher in diabetic patients indicating endothelial oxidative stress. PKCβ expression was higher in diabetic patients and was associated with lower flow-mediated dilation (r=−0.541, P=0.02) Inhibition of PKCβ with LY379196 reduced basal eNOS phosphorylation and improved insulin-mediated eNOS activation in patients with diabetes. Endothelial NFκB activation was higher in diabetes and was reduced with PKCβ inhibition. Conclusions We provide evidence for the presence of altered eNOS activation, reduced insulin action and inflammatory activation in the endothelium of patients with diabetes. Our findings implicate PKCβ activity in endothelial insulin resistance. PMID:23204109

  5. Prevention of cognitive impairment in diabetic rats with oral magnesium sulfate

    Directory of Open Access Journals (Sweden)

    Gharibzadeh Sh

    2007-11-01

    Full Text Available Background: Diabetes mellitus is a common metabolic disorder accompanied with structural and functional changes in central and peripheral nervous system. Researches showed, memory disturbance were occurred in the course of diabetes. On the other hand, magnesium deficit has been described in diabetic patients. Some researches were showed that, appropriate magnesium supplementation can play a positive role in diabetic control.Methods: Locally produced male rats were used. Diabetes was induced with intravenous injection of 40 mg/kg streptozotosin. In treatment groups, the animals were received magnesium sulfate via drinking water (10 g/l. Eight weeks after diabetes confirmation, the animals were assessed on Morris Water Maze.Results: A significant decrease in time of platform finding (latency and distance of swimming in all four experimental days were seen in all groups. Mean latency in diabetic group was significantly higher than the other. This weak response was almost completely prevented by magnesium sulfate administration.Conclusion: It seems that after eight weeks magnesium sulfate administration (10g/l, spatial memory of the animals was improved in comparison to diabetic group that can suggest role of magnesium in recovery of diabetic animal memory.

  6. Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study

    Science.gov (United States)

    Reynolds, Rebecca M; Labad, Javier; Sears, Alison V; Williamson, Rachel M; Strachan, Mark W J; Deary, Ian J; Lowe, Gordon D O; Price, Jackie F; Walker, Brian R

    2012-01-01

    Objective Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects. Design Cross-sectional cohort study. Methods Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids. Results Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle–brachial pressure index. Conclusions Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function. PMID:22408122

  7. Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging

    Directory of Open Access Journals (Sweden)

    Ji Won Yoon

    2016-03-01

    Full Text Available BackgroundThe study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes.MethodsThis was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30 and uncertainty about the diagnosis of diabetes (n=27. Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass.ResultsThe muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045 after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%.ConclusionPoor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.

  8. Cognitive impairment and dependence of patients with diabetes older than 65 years old in an urban area (DERIVA study).

    Science.gov (United States)

    Rodríguez-Sánchez, Emiliano; Mora-Simón, Sara; Patino-Alonso, María C; Pérez-Arechaederra, Diana; Recio-Rodríguez, José I; Gómez-Marcos, Manuel A; Valero-Juan, Luis F; García-Ortiz, Luis

    2016-02-01

    We analyzed the associations between diabetes and cognitive impairment (CI) and dependence in a population of patients 65 years or older. Cross-sectional study. We randomly selected 311 participants over the age of 65 living in an urban area of Spain. The mean age of the cohort was 75.89 ± 7.12 years, and 69 of the individuals (22.2%) had diabetes. Two questionnaires were used to assess cognitive performance (MMSE and Seven Minute Screen Test), and two assessments were used to evaluate patient dependence (Barthel Index and Lawton-Brody Index). Clinical information and sociodemographic data were also gathered. Nearly one quarter of patients with diabetes (21.7%) lived alone. Diabetic patients were more sedentary (p = .033) than non-diabetic patients. Roughly one sixth (15.3%) of the diabetics and 10.1% of the non-diabetics were depressed (p = .332). CI was present in 26.1% of the diabetics and 14.5% of non-diabetics (p = .029). Diabetic patients had a MMSE score that was significantly worse than non-diabetics (24.88 ± 4.74 vs 26.05 ± 4.03; p cognitive assessment as necessary components in a standard evaluation in both clinical guides and randomized trials of therapeutic interventions in patients with diabetes.

  9. Glucocorticoid-mediated activation of GSK3β promotes tau phosphorylation and impairs memory in type 2 diabetes.

    Science.gov (United States)

    Dey, Aditi; Hao, Shuai; Wosiski-Kuhn, Marlena; Stranahan, Alexis M

    2017-09-01

    Type 2 diabetes is increasingly recognized as a risk factor for Alzheimer's disease, but the underlying mechanisms remain poorly understood. Hyperphosphorylation of the microtubule-associated protein tau has been reported in rodent models of diabetes, including db/db mice, which exhibit insulin resistance and chronically elevated glucocorticoids due to leptin receptor insufficiency. In this report, we investigated endocrine mechanisms for hippocampal tau phosphorylation in db/db and wild-type mice. By separately manipulating peripheral and intrahippocampal corticosterone levels, we determined that hippocampal corticosteroid exposure promotes tau phosphorylation and activates glycogen synthase kinase 3β (GSK3β). Subsequent experiments in hippocampal slice preparations revealed evidence for a nongenomic interaction between glucocorticoids and GSK3β. To examine whether GSK3β activation mediates tau phosphorylation and impairs memory in diabetes, db/db and wild-type mice received intrahippocampal infusions of TDZD-8, a non-ATP competitive thiadiazolidinone inhibitor of GSK3β. Intrahippocampal TDZD-8 blocked tau hyperphosphorylation and normalized hippocampus-dependent memory in db/db mice, suggesting that pathological synergy between diabetes and Alzheimer's disease may involve glucocorticoid-mediated activation of GSK3β. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. [Comparative study on oral candidal infection in individuals with diabetes mellitus and impaired glucose regulation].

    Science.gov (United States)

    Huang, Jing-hua; Liu, Yang; Liu, Hong-wei

    2012-06-01

    To investigate the positive rate, infection rate and bearing rate of salivary candida in patients with type 2 diabetes mellitus (DM), individuals with impaired glucose regulation (IGR) and individuals with normal glucose tolerance (NGT) and their predisposing factors. Questionnaire was given to 145 patients with DM, 142 individuals with IGR and 149 NGT individuals. Oral examination was carried out, and fasting plasma glucose (FPG) level and plasma glucose level of 2 hours post glucose-load (PG2h), resting salivary flow, salivary pH value were tested. Salivary candida was cultured. In DM, IGR and NGT groups, the positive rates of salivary candida were 21.4% (31/145), 7.0% (10/142), 4.7% (7/149) respectively, the infection rates were 7.6% (11/145), 1.4% (2/142), 1.3% (2/149) respectively, and the bearing rates of salivary candida were 13.8% (20/145), 5.6% (8/142), 3.4% (5/149) respectively. The candida positive rate, candida infection rate in DM group were higher than those of IGR and NGT groups respectively (P 0.05). Resting salivary flow in DM [(1.30 ± 1.20) ml/10 min] and IGR [(1.40 ± 1.17) ml/10 min]groups were lower than that in NGT group [(1.93 ± 1.66) ml/10 min], salivary pH values in DM (7.11 ± 0.56) and IGR (7.05 ± 0.48) groups were lower than that in NGT group (7.38 ± 0.48) (P salivary candida was influenced to some degree by age, FPG level and bearing denture (OR value = 1.106, 1.258, 3.166). The patients with DM were more subjected to bearing or infection of candida than individuals with IGR and NGT. To control the plasma glucose level will help to decrease the positive rate and infection rate of oral candida.

  11. Erectile dysfunction and diabetes: Association with the impairment of lipid metabolism and oxidative stress.

    Science.gov (United States)

    Belba, Arben; Cortelazzo, Alessio; Andrea, Giansanti; Durante, Jacopo; Nigi, Laura; Dotta, Francesco; Timperio, Anna Maria; Zolla, Lello; Leoncini, Roberto; Guerranti, Roberto; Ponchietti, Roberto

    2016-01-01

    To test the hypothesis that exists an association of non-diabetic and diabetic patients suffering from erectile dysfunction (ED) with lipid metabolism and oxidative stress. Clinical and laboratory characteristics in non-diabetic (n = 30, middle age range: 41–55.5 years; n = 25, old age range: 55.5–73), diabetic ED patients (n = 30, age range: 55.5–75 years) and diabetic patients (n = 25, age range: 56–73.25), were investigated. Proteomic analysis was performed to identify differentially expressed plasma proteins and to evaluate their oxidative posttranslational modifications. A decreased level of high-density lipoproteins in all ED patients (P < 0.001, C.I. 0.046–0.10), was detected by routine laboratory tests. Proteomic analysis showed a significant decreased expression (P < 0.05) of 5 apolipoproteins (i.e. apolipoprotein H, apolipoprotein A4, apolipoprotein J, apolipoprotein E and apolipoprotein A1) and zinc-alpha-2-glycoprotein, 50% of which are more oxidized proteins. Exclusively for diabetic ED patients, oxidative posttranslational modifications for prealbumin, serum albumin, serum transferrin and haptoglobin markedly increased. Showing evidence for decreased expression of apolipoproteins in ED and the remarkable enhancement of oxidative posttranslational modifications in diabetes-associated ED, considering type 2 diabetes mellitus and age as independent risk factors involved in the ED pathogenesis, lipid metabolism and oxidative stress appear to exert a complex interplay in the disease.

  12. Impaired autoregulation of glomerular filtration rate in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, Helge; Smidt, U M

    1984-01-01

    The effect of acute lowering of arterial blood pressure upon kidney function in nephropathy was studied in 13 patients with long-term Type 1 (insulin-dependent) diabetes. Ten normal subjects (six normotensive and four hypertensive) and five short-term Type 1 diabetic patients without nephropathy...

  13. The threshold for diagnosing impaired fasting glucose : a position statement by the European Diabetes Epidemiology Group

    NARCIS (Netherlands)

    Forouhi, NG; Balkau, B; Borch-Johnsen, K; Dekker, J; Glumer, C; Qiao, Q; Spijkerman, A; Stolk, R; Tabac, A; Wareham, NJ

    The category of IFG was introduced in the late 1990s to denote a state of non-diabetic hyperglycaemia defined by a fasting plasma glucose (FPG) concentration between 6.1 and 6.9 mmol/l. In 2003 the American Diabetes Association recommended that this diagnostic threshold be lowered to 5.6 mmol/l. The

  14. Prevalence and progression of visual impairment in patients newly diagnosed with clinical type 2 diabetes: a 6-year follow up study

    Directory of Open Access Journals (Sweden)

    Almind Gitte

    2011-02-01

    Full Text Available Abstract Background Many diabetic patients fear visual loss as the worst consequence of diabetes. In most studies the main eye pathology is assigned as the cause of visual impairment. This study analysed a broad range of possible ocular and non-ocular predictors of visual impairment prospectively in patients newly diagnosed with clinical type 2 diabetes. Methods Data were from a population-based cohort of 1,241 persons newly diagnosed with clinical, often symptomatic type 2 diabetes aged ≥ 40 years. After 6 years, 807 patients were followed up. Standard eye examinations were done by practising ophthalmologists. Results At diabetes diagnosis median age was 65.5 years. Over 6 years, the prevalence of blindness (visual acuity of best seeing eye ≤ 0.1 rose from 0.9% (11/1,241 to 2.4% (19/807 and the prevalence of moderate visual impairment (> 0.1; Conclusions In a comprehensive assessment of predictors of visual impairment, even in a health care system allowing self-referral to free eye examinations, treatable eye pathologies such as DR and cataract emerge together with age as the most notable predictors of continued visual loss after diabetes diagnosis. Our results underline the importance of eliminating barriers to efficient eye care by increasing patients' and primary care practitioners' awareness of the necessity of regular eye examinations and timely surgical treatment.

  15. G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans

    DEFF Research Database (Denmark)

    Sparsø, Thomas; Bonnefond, Amélie; Andersson, Ehm

    2009-01-01

    independent effect on FPG with isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), type 2 diabetes, and measures of insulin release and peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS: We examined European-descent participants in the Inter99 study...... (n = 5,553), in a sample of young healthy Danes (n = 372), in Danish twins (n = 77 elderly and n = 97 young), in additional Danish type 2 diabetic patients (n = 1,626) and control subjects (n = 505), in the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study (n = 4...

  16. The metabolites in peripheral blood mononuclear cells showed greater differences between patients with impaired fasting glucose or type 2 diabetes and healthy controls than those in plasma.

    Science.gov (United States)

    Kim, Minjoo; Kim, Minkyung; Han, Ji Yun; Lee, Sang-Hyun; Jee, Sun Ha; Lee, Jong Ho

    2017-03-01

    To determine differences between peripheral blood mononuclear cells and the plasma metabolites in patients with impaired fasting glucose or type 2 diabetes and healthy controls. In all, 65 nononobese patients (aged 30-70 years) with impaired fasting glucose or type 2 diabetes and 65 nonobese sex-matched healthy controls were included, and fasting peripheral blood mononuclear cell and plasma metabolomes were profiled. The diabetic or impaired fasting glucose patients showed higher circulating and peripheral blood mononuclear cell lipoprotein phospholipase A 2 activities, high-sensitivity C-reactive protein and tumour necrosis factor-α than controls. Compared with controls, impaired fasting glucose or diabetic subjects showed increases in 11 peripheral blood mononuclear cell metabolites: six amino acids (valine, leucine, methionine, phenylalanine, tyrosine and tryptophan), l-pyroglutamic acid, two fatty acid amides containing palmitic amide and oleamide and two lysophosphatidylcholines. In impaired fasting glucose or diabetic patients, peripheral blood mononuclear cell lipoprotein phospholipase A 2 positively associated with peripheral blood mononuclear cell lysophosphatidylcholines and circulating inflammatory markers, including tumour necrosis factor-α, high-sensitivity C-reactive protein and lipoprotein phospholipase A 2 activities. In plasma metabolites between patients and healthy controls, we observed significant increases in only three amino acids (proline, valine and leucine) and decreases in only five lysophosphatidylcholines. This study demonstrates significant differences in the peripheral blood mononuclear cell metabolome in patients with impaired fasting glucose or diabetes compared with healthy controls. These differences were greater than those observed in the plasma metabolome. These data suggest peripheral blood mononuclear cells as a useful tool to better understand the inflammatory pathophysiology of diabetes.

  17. Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Subbuswamy K. Prabu

    2011-05-01

    Full Text Available We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks. These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III and cytochrome c oxidase (Complex IV were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I and succinate:ubiquinone oxidoreductase (Complex II were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.

  18. Impaired mitochondrial metabolism and protein synthesis in streptozotocin diabetic rat hepatocytes

    International Nuclear Information System (INIS)

    Memon, R.A.; Bessman, S.P.; Mohan, C.

    1990-01-01

    Isolated hepatocytes prepared from control, streptozotocin diabetic rats were incubated at 30 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, containing 0.5 mM concentration of each of the 20 natural amino acids. Effect of insulin on the oxidation of 2,3- 14 C and 1,4- 14 C succinate (suc) carbons and their incorporation into hepatocyte protein, lipid and various metabolic intermediates was studied. Mitochondrial oxidation of suc carbons and their incorporation into protein and lipid was significantly lower in diabetic and insulin treated diabetic rats. Diabetic rats failed to exhibit any significant insulin effect on the oxidation of either 2,3 or 1,4- 14 C suc carbons. Amphibolic channeling of 2,3- 14 C suc carbons into amino acids was significantly reduced in hepatocytes of diabetic rats, however, more of these carbons were diverted into the gluconeogenesis pathway. Diabetes caused a far greater decrease in the oxidation of 2,3- 14 C suc carbons as compared to 1,4- 14 C suc. Based on an earlier report that insulin stimulates only the intramitochondrial Krebs cycle reactions, the authors conclude that the diminished level of anabolic activities in the diabetic rat hepatocytes is due to the subsequent reduction in amphibolic channeling of metabolic intermediates

  19. Impaired pancreatic polypeptide response to a meal in type 1 diabetic patients

    DEFF Research Database (Denmark)

    Rasmussen, M H; Carstensen, H; List, S

    1993-01-01

    The pancreatic polypeptide (PP) response to a mixed meal was investigated in seven insulin-dependent diabetics without measurable signs of diabetic autonomic neuropathy, and in seven healthy subjects. Since acute changes in metabolic regulation might influence the meal-induced PP response...... is independent of short-term changes in metabolic control. Since the response was attenuated in the insulin-dependent diabetic patients, who had no otherwise measurable signs of neuropathy, the PP response to a meal could be a sensitive indicator of dysfunction of the reflex arc controlling PP secretion...

  20. Dynamic Changes of Neuroskeletal Proteins in DRGs Underlie Impaired Axonal Maturation and Progressive Axonal Degeneration in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Hideki Kamiya

    2009-01-01

    Full Text Available We investigated mechanisms underlying progressive axonal dysfunction and structural deficits in type 1 BB/Wor-rats from 1 week to 10 month diabetes duration. Motor and sensory conduction velocities were decreased after 4 and 6 weeks of diabetes and declined further over the remaining 9 months. Myelinated sural nerve fibers showed progressive deficits in fiber numbers and sizes. Structural deficits in unmyelinated axonal size were evident at 2 month and deficits in number were present at 4 mo. These changes were preceded by decreased availability of insulin, C-peptide and IGF-1 and decreased expression of neurofilaments and β-III-tubulin. Upregulation of phosphorylating stress kinases like Cdk5, p-GSK-3β, and p42/44 resulted in increased phosphorylation of neurofilaments. Increasing activity of p-GSK-3β correlated with increasing phosphorylation of NFH, whereas decreasing Cdk5 correlated with diminishing phosphorylation of NFM. The data suggest that impaired neurotrophic support results in sequentially impaired synthesis and postranslational modifications of neuroskeletal proteins, resulting in progressive deficits in axonal function, maturation and size.

  1. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

    Science.gov (United States)

    Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

    2011-12-01

    Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

  2. Association between diabetes mellitus and hearing impairment in American and Korean populations.

    Science.gov (United States)

    Moon, Shinje; Park, Jung Hwan; Yu, Jae Myung; Choi, Moon-Ki; Yoo, Hyung Joon

    2018-04-20

    The aim of this study was to evaluate ethnic- and sex-specific associations between DM and hearing impairment. For this cross-sectional study using National Health and Nutrition Examination Survey in the U.S. and Korea, the total number of eligible participants included was 7081 in the U.S. and 15,704 in Korea. Hearing impairment was defined as a pure tone threshold level ≥ 25 dB. Multivariate logistic regression analysis was conducted, adjusting for age, sex, race/ethnicity, socioeconomic status, body mass index, noise exposure, smoking, hypertension, and dyslipidemia. The association between DM and hearing impairment was found to be sex-specific. The multivariate adjusted ORs of high-frequency impairment were 0.843 (95% CI, 0.524-1.356) in American men, and 1.073 (95% CI, 0.835-1.379) in Korean men, while the ORs in women from U.S. and Korea were 1.911 (95% CI, 1.244-2.935) and 1.421 (95% CI, 1.103-1.830), respectively. A subgroup analysis of each race/ethnicity among the U.S. adults showed similar results. In contrast to high-frequency impairment, there was no significant association between low-frequency impairment and DM in both men and women. Our results suggest that DM is associated with hearing impairment in only women, irrespective of race/ethnicity groups. Copyright © 2018. Published by Elsevier Inc.

  3. Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA(1c) and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4).

    Science.gov (United States)

    Heianza, Y; Arase, Y; Fujihara, K; Tsuji, H; Saito, K; Hsieh, S D; Kodama, S; Shimano, H; Yamada, N; Hara, S; Sone, H

    2012-09-01

    To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA(1c) values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals. The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA(1c) ≥ 48 mmol/mol (≥ 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l or 6.1-6.9 mmol/l) and elevated HbA(1c) [39-46 mmol/mol (5.7-6.4%) or 42-46 mmol/mol (6.0-6.4%)]. During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.5-32.0% reverted to the normoglycaemic state as having neither elevated HbA(1c) nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l had a 100% cumulative risk of developing diabetes. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l would predict definite progression to diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  4. Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia.

    Science.gov (United States)

    Vukovic, R; Mitrovic, K; Milenkovic, T; Todorovic, S; Zdravkovic, D

    2012-11-01

    An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2-18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.

  5. Global Longitudinal Strain Is Not Impaired in Type 1 Diabetes Patients Without Albuminuria

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Sogaard, Peter; Andersen, Henrik Ullits

    2015-01-01

    suggested. It is not known whether myocardial dysfunction is a feature of T1DM per se or primarily associated with diabetes with albuminuria. METHODS: This cross-sectional study compared 1,065 T1DM patients without known heart disease from the outpatient clinic at the Steno Diabetes Center with 198 healthy......OBJECTIVES: The purpose of this study was to investigate if systolic myocardial function is reduced in all patients with type 1 diabetes (T1DM) or only in patients with albuminuria. BACKGROUND: Heart failure is a common cause of mortality in T1DM, and a specific diabetic cardiomyopathy has been...... mass index 25.5 kg/m(2), and mean diabetes duration 26.1 years. In unadjusted analyses, GLS differed significantly between T1DM patients and control subjects (p = 0.02). When stratified by degrees of albuminuria, the difference in GLS compared with control subjects was -18.8 ± 2.5% versus -18.5 ± 2...

  6. Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

    Science.gov (United States)

    Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

    2016-07-01

    New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

  7. Peculiarities of Ischemic Heart Disease Course and Treatment in Patients with Glucose Metabolism Impairment and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    O.M. Radchenko

    2015-09-01

    Full Text Available Combination of ischemic heart disease and diabetes mellitus is characterized by certain features of clinical picture and insufficient effectiveness of treatment of ischemic heart disease. With the aim of investigation of pathogenic mechanisms and features of the clinical course of ischemic heart disease associated with glucose homeostasis violation we examined 116 patients (51 women, 65 men, median of age 63 years old with normal regulation of glucose metabolism (NRG, n = 24, changes in fasting glucose (n = 23, violated glucose tolerance (n = 21, combined violation (n = 24 and diabetes mellitus (n = 24. We also conducted their prospective observation for 40 months with the following endpoints — hospitalization because of cardiovascular complications, death from them and the emergence of diabetes. It was established that ischemic heart disease associated with prediabetic disorders and diabetes mellitus has the following peculiarities: earlier clinical manifestation in women; more frequent and severe heart failure; lower tolerance to physical load in patients with angina pectoris; atypical manifestation of ischemic pain: longer attacks, atypical localization or absent pain; frequent combination with arrhythmias and conduction disorders; frequent affection of multiple coronary arteries, which leads to myocardial infarction with complicated course; eccentric type of left ventricle remodeling; significant calcification of mitral and aortic valves of heart. The main principles of treatment of ischemic heart disease: weight loss; active correction of glucose metabolism violations using medications (metformin even at the stage of prediabetes, because in chronic stable forms of ischemic heart disease metformin significantly improves glucose metabolism, decreases insulin resistance and does not increase the incidence of cardiovascular complications and decompensations of heart failure; the basic drugs for treatment of ischemic heart disease should be

  8. ATP synthesis is impaired in isolated mitochondria from myotubes established from type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Minet, Ariane D; Gaster, Michael

    2010-01-01

    To date, it is unknown whether mitochondrial dysfunction in skeletal muscle from subjects with type 2 diabetes is based on primarily reduced mitochondrial mass and/or a primarily decreased mitochondrial ATP synthesis. Mitochondrial mass were determined in myotubes established from eight lean, eight...... mass and the ATP synthesis rate, neither at baseline nor during acute insulin stimulation, were not different between groups. The ratio of ATP synthesis rate at hexokinase versus ATP synthesis rate at baseline was lower in diabetic mitochondria compared to lean mitochondria. Thus the lower content...... obese and eight subjects with type 2 diabetes precultured under normophysiological conditions. Furthermore, mitochondria were isolated and ATP production was measured by luminescence at baseline and during acute insulin stimulation with or without concomitant ATP utilization by hexokinase. Mitochondrial...

  9. Bridging the gap between neurocognitive processing theory and performance validity assessment among the cognitively impaired: a review and methodological approach.

    Science.gov (United States)

    Leighton, Angela; Weinborn, Michael; Maybery, Murray

    2014-10-01

    Bigler (2012) and Larrabee (2012) recently addressed the state of the science surrounding performance validity tests (PVTs) in a dialogue highlighting evidence for the valid and increased use of PVTs, but also for unresolved problems. Specifically, Bigler criticized the lack of guidance from neurocognitive processing theory in the PVT literature. For example, individual PVTs have applied the simultaneous forced-choice methodology using a variety of test characteristics (e.g., word vs. picture stimuli) with known neurocognitive processing implications (e.g., the "picture superiority effect"). However, the influence of such variations on classification accuracy has been inadequately evaluated, particularly among cognitively impaired individuals. The current review places the PVT literature in the context of neurocognitive processing theory, and identifies potential methodological factors to account for the significant variability we identified in classification accuracy across current PVTs. We subsequently evaluated the utility of a well-known cognitive manipulation to provide a Clinical Analogue Methodology (CAM), that is, to alter the PVT performance of healthy individuals to be similar to that of a cognitively impaired group. Initial support was found, suggesting the CAM may be useful alongside other approaches (analogue malingering methodology) for the systematic evaluation of PVTs, particularly the influence of specific neurocognitive processing components on performance.

  10. Decreased systolic blood pressure is associated with increased risk of all-cause mortality in patients with type 2 diabetes and renal impairment: A nationwide longitudinal observational study of 27,732 patients based on the Swedish National Diabetes Register.

    Science.gov (United States)

    Svensson, Maria K; Afghahi, Henri; Franzen, Stefan; Björk, Staffan; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Eliasson, Björn

    2017-05-01

    Previous studies have shown a U-shaped relationship between systolic blood pressure and risk of all-cause of mortality in patients with type 2 diabetes and renal impairment. To evaluate the associations between time-updated systolic blood pressure and time-updated change in systolic blood pressure during the follow-up period and risk of all-cause mortality in patients with type 2 diabetes and renal impairment. A total of 27,732 patients with type 2 diabetes and renal impairment in the Swedish National Diabetes Register were followed for 4.7 years. Time-dependent Cox models were used to estimate risk of all-cause mortality. Time-updated mean systolic blood pressure is the average of the baseline and the reported post-baseline systolic blood pressures. A time-updated systolic blood pressure blood pressure > 10 mmHg between the last two observations was associated with higher risk of all-cause mortality (-10 to -25 mmHg; hazard ratio: 1.24, 95% confidence interval: 1.17-1.32). Both low systolic blood pressure and a decrease in systolic blood pressure during the follow-up are associated with a higher risk of all-cause mortality in patients with type 2 diabetes and renal impairment.

  11. Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højlund, K.; Frystyk, J.; Levin, K.

    2006-01-01

    AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear...... (ten lean, 21 obese and 20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes...... by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes....

  12. Myocardial impulse propagation is impaired in right ventricular tissue of Zucker Diabetic Fatty (ZDF) rats

    DEFF Research Database (Denmark)

    Olsen, Kristine Boisen; Axelsen, Lene Nygaard; Braunstein, Thomas Hartig

    2013-01-01

    Diabetes increases the risk of cardiovascular complications including arrhythmias, but the underlying mechanisms remain to be established. Decreased conduction velocity (CV), which is an independent risk factor for re-entry arrhythmias, is present in models with streptozotocin (STZ) induced type ...

  13. Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients

    Directory of Open Access Journals (Sweden)

    Morana Jaganjac

    2017-08-01

    Full Text Available Objective: Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM. This study investigated whether impaired adipogenesis of omental (OM adipose tissues and elevated 4-hydroxynonenal (4-HNE accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. Methods: OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. Results: Preadipocytes isolated from insulin resistant (IR and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. Conclusion: This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic

  14. Upregulation of CREM/ICER suppresses wound endothelial CRE-HIF-1α-VEGF-dependent signaling and impairs angiogenesis in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Milad S. Bitar

    2015-01-01

    Full Text Available Impaired angiogenesis and endothelial dysfunction in type 2 diabetes constitute dominant risk factors for non-healing wounds and most forms of cardiovascular disease. We propose that diabetes shifts the ‘angiogenic balance’ in favor of an excessive anti-angiogenic phenotype. Herein, we report that diabetes impairs in vivo sponge angiogenic capacity by decreasing VEGF expression and fibrovascular invasion, and reciprocally enhances the formation of angiostatic molecules, such as thrombospondins, NFκB and FasL. Defective in vivo angiogenesis prompted cellular studies in cultured endothelial cells derived from subcutaneous sponge implants (SIECs of control and Goto-Kakizaki rats. Ensuing data from diabetic SIECs demonstrated a marked upregulation in cAMP-PKA-CREB signaling, possibly stemming from increased expression of adenylyl cyclase isoforms 3 and 8, and decreased expression of PDE3. Mechanistically, we found that oxidative stress and PKA activation in diabetes enhanced CREM/ICER expression. This reduces IRS2 cellular content by inhibiting cAMP response element (CRE transcriptional activity. Consequently, a decrease in the activity of Akt-mTOR ensued with a concomitant reduction in the total and nuclear protein levels of HIF-1α. Limiting HIF-1α availability for the specific hypoxia response elements in diabetic SIECs elicited a marked reduction in VEGF expression, both at the mRNA and protein levels. These molecular abnormalities were illustrated functionally by a defect in various pro-angiogenic properties, including cell proliferation, migration and tube formation. A genetic-based strategy in diabetic SIECs using siRNAs against CREM/ICER significantly augmented the PKA-dependent VEGF expression. To this end, the current data identify the importance of CREM/ICER as a negative regulator of endothelial function and establish a link between CREM/ICER overexpression and impaired angiogenesis during the course of diabetes. Moreover, it could

  15. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion

    DEFF Research Database (Denmark)

    Lyssenko, Valeriya; Nagorny, Cecilia L F; Erdos, Michael R

    2009-01-01

    Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype...... was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets....... Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which...

  16. Impaired beta cell sensitivity to incretins in type 2 diabetes is insufficiently compensated by higher incretin response

    DEFF Research Database (Denmark)

    Tura, A.; Bagger, J. I.; Ferrannini, E.

    2017-01-01

    Background and aims The incretin effect is impaired in type 2 diabetes (T2D), but the underlying mechanisms are only partially understood. We investigated the relationships between the time course of the incretin effect and that of glucose-dependent insulinotropic polypeptide (GIP) and glucagon......-like peptide-1 (GLP-1) during oral glucose tolerance tests (OGTTs), thereby estimating incretin sensitivity of the beta cell, and its associated factors. Methods and results Eight patients with T2D and eight matched subjects with normal glucose tolerance (NGT) received 25, 75, and 125 g OGTTs and corresponding...... was correlated with that of both GIP and GLP-1 in each subject (median r = 0.67 in NGT and 0.45 in T2D). We calculated an individual beta cell sensitivity to incretins (SINCR) using a weighted average of GIP and GLP-1 (pooled incretin concentration, PIC), as the slope of the relationship between PINCR and PIC...

  17. Impaired postprandial fullness in Type 2 diabetic subjects is rescued by acute exercise independently of total and acylated ghrelin

    DEFF Research Database (Denmark)

    Knudsen, Sine H; Karstoft, Kristian; Solomon, Thomas

    2013-01-01

    Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels...... in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could...... be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions...

  18. Carotid intima-media thickness is reduced 12 months after gastric bypass surgery in obese patients with type 2 diabetes or impaired glucose tolerance

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Tarnow, Lise; Hansen, Dorte L

    2014-01-01

    AIM: To investigate whether Roux-en-Y gastric bypass surgery (RYGB) - an in vivo model for normalisation of hyperglycaemia - improves carotid intima-media thickness (IMT) in patients with type 2 diabetes (T2D)/impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). METHODS: Observati...

  19. Impaired trophoblast invasion and increased numbers of immune cells at day 18 of pregnancy in the mesometrial triangle of type 1 diabetic rats

    NARCIS (Netherlands)

    Groen, B.; Uuldriks, G. A.; de Vos, P.; Visser, J. T.; Links, T. P.; Faas, M. M.

    Introduction: Type 1 diabetes (T1D) is associated with adverse pregnancy outcome, usually attributed to hyperglycemia. Recently, we showed that pregnancy outcome in normoglycemic T1D rats was characterized by decreased fetal and placental weight, suggesting impaired placental development. In the

  20. Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial

    NARCIS (Netherlands)

    van Beers, Cornelis A. J.; DeVries, J. Hans; Kleijer, Susanne J.; Smits, Mark M.; Geelhoed-Duijvestijn, Petronella H.; Kramer, Mark H. H.; Diamant, Michaela; Snoek, Frank J.; Serné, Erik H.

    2016-01-01

    Patients with type 1 diabetes who have impaired awareness of hypoglycaemia have a three to six times increased risk of severe hypoglycaemia. We aimed to assess whether continuous glucose monitoring (CGM) improves glycaemia and prevents severe hypoglycaemia compared with self-monitoring of blood

  1. Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A.

    Science.gov (United States)

    Kogawa, Evelyn Mikaela; Grisi, Daniela Corrêa; Falcão, Denise Pinheiro; Amorim, Ingrid Aquino; Rezende, Taia Maria Berto; da Silva, Izabel Cristina Rodrigues; Silva, Osmar Nascimento; Franco, Octávio Luiz; de Amorim, Rivadávio Fernandes Batista

    2016-11-01

    The purpose of this study was to evaluate the effect of type 2 diabetes mellitus (T2DM) on salivary function impairments according to glycemic control status and subsequently compare the concentration of chromogranin A (CHGA) with its genetic profile. Thirty-six patients with controlled T2DM, 36 with poorly controlled T2DM, and 38 nondiabetic subjects underwent salivary flow rate measurements by means of unstimulated labial (ULS), unstimulated whole (UWS), and stimulated whole saliva (SWS) collections. CHGA concentrations were determined in saliva and plasma with ELISA, and two CHGA polymorphisms (T-415C and Glu264Asp) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. T2DM patients presented significantly lower ULS and UWS flow rates regardless of glycemic control status compared to controls (P = 0.002 and P = 0.027, respectively). The SWS flow rate in the poorly controlled T2DM was the lowest among the groups (P = 0.026). Significantly higher plasma and salivary CHGA levels were found in T2DM groups (P = 0.019 and P diabetics and control subjects when associated with lower salivary flow and higher salivary CHGA production (P salivary glands. However, poorly controlled T2DM has the most influence on SWS flow rates. Our findings indicate an association between plasma and salivary CHGA levels and T2DM patients. Furthermore, the results suggest that CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. Nevertheless, further epidemiological studies are required to elucidate this clinical implication. Salivary impairments and high levels of CHGA are associated with T2DM patients. In addition, CGHA polymorphisms might be associated with salivary gland hypofunction and higher salivary CHGA production in T2DM patients. This could be a significant insight to establish a role for salivary CHGA as a potential clinical biomarker to T2DM.

  2. Type 2 diabetes impairs venous, but not arterial smooth muscle cell function: Possible role of differential RhoA activity

    Energy Technology Data Exchange (ETDEWEB)

    Riches, Kirsten [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Warburton, Philip [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); O’Regan, David J. [Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Department of Cardiac Surgery, The Yorkshire Heart Centre, Leeds General Infirmary, Leeds (United Kingdom); Turner, Neil A. [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular and Diabetes Research, Leeds Institute of Genetics, Health and Therapeutics (LIGHT), University of Leeds, Leeds (United Kingdom); Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds (United Kingdom)

    2014-04-15

    Background/purpose: Coronary heart disease is the leading cause of morbidity in patients with type 2 diabetes mellitus (T2DM), frequently resulting in a requirement for coronary revascularization using the internal mammary artery (IMA) or saphenous vein (SV). Patency rates of SV grafts are inferior to IMA and further impaired by T2DM whilst IMA patencies appear similar in both populations. Smooth muscle cells (SMC) play a pivotal role in graft integration; we therefore examined the phenotype and proliferative function of IMA- and SV-SMC isolated from non-diabetic (ND) patients or those diagnosed with T2DM. Methods/materials: SMC were cultured from fragments of SV or IMA. Morphology was analyzed under light microscopy (spread cell area measurements) and confocal microscopy (F-actin staining). Proliferation was analyzed by cell counting. Levels of RhoA mRNA, protein and activity were measured by real-time RT-PCR, western blotting and G-LISA respectively. Results: IMA-SMC from T2DM and ND patients were indistinguishable in both morphology and function. By comparison, SV-SMC from T2DM patients exhibited significantly larger spread cell areas (1.5-fold increase, P < 0.05), truncated F-actin fibers and reduced proliferation (33% reduction, P < 0.05). Furthermore, lower expression and activity of RhoA were observed in SV-SMC of T2DM patients (37% reduction in expression, P < 0.05 and 43% reduction in activity, P < 0.01). Conclusions: IMA-SMC appear impervious to phenotypic modulation by T2DM. In contrast, SV-SMC from T2DM patients exhibit phenotypic and functional changes accompanied by reduced RhoA activity. These aberrancies may be epigenetic in nature, compromising SMC plasticity and SV graft adaptation in T2DM patients. Summary: The internal mammary artery (IMA) is the conduit of choice for bypass grafting and is generally successful in all patients, including those with type 2 diabetes (T2DM). By contrast, saphenous vein (SV) is inferior to IMA and furthermore

  3. Frequency of diabetes, impaired fasting glucose, and glucose intolerance in high-risk groups identified by a FINDRISC survey in Puebla City, Mexico

    Directory of Open Access Journals (Sweden)

    Hirales-Tamez O

    2012-11-01

    Full Text Available Hector García-Alcalá, Christelle Nathalie Genestier-Tamborero, Omara Hirales-Tamez, Jorge Salinas-Palma, Elena Soto-VegaFaculty of Medicine, Universidad Popular Autónoma del Estado de Puebla, Puebla Pue, MexicoBackground: As a first step in the prevention of diabetes, the International Diabetes Federation recommends identification of persons at risk using the Finnish type 2 Diabetes Risk Assessment (FINDRISC survey. The frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in high-risk groups identified by FINDRISC is unknown in our country. The aim of this study was to determine the frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in higher-risk groups using a FINDRISC survey in an urban population.Methods: We used a television program to invite interested adults to fill out a survey at a television station. An oral glucose tolerance test was performed in all persons with a FINDRISC score ≥ 15 points (high-risk and very high-risk groups. Patients were classified as normal (fasting glucose < 100 mg/dL and 2-hour glucose < 140 mg/dL, or having impaired fasting glucose (fasting glucose 100–125 mg/dL and 2-hour glucose < 140 mg/dL, glucose intolerance (fasting glucose < 126 mg/dL and 2-hour glucose 140–199 mg/dL, and diabetes mellitus (fasting glucose ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL. We describe the frequency of each diagnostic category in this selected population according to gender and age.Results: A total of 186 patients had a score ≥ 15. The frequencies of diabetes mellitus, impaired fasting glucose, glucose intolerance, and normal glucose levels were 28.6%, 25.9%, 29.2%, and 16.2%, respectively. We found a higher frequency of diabetes mellitus and impaired fasting glucose in men than in women (33% versus 27% and 40% versus 21%, respectively and more glucose intolerance in women than in men (34% versus 16%, P < 0.05. Patients with diabetes mellitus (52.55 ± 9

  4. Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes

    DEFF Research Database (Denmark)

    Hendrieckx, Crystal; Jenkins, A; Hagger, Virginia

    2017-01-01

    AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with ty...... autonomic symptoms, perceived at relatively low glucose levels. Frequent self-monitoring of blood glucose prompted early recognition and treatment of hypoglycemia, suggesting severe hypoglycemia risk can be minimized.......AIMS: To assess prevalence of severe hypoglycemia, awareness and symptoms of hypoglycemia, and their associations with self-monitoring of blood glucose. METHODS: Diabetes MILES-Australia Study participants completed validated questionnaires and study-specific items. RESULTS: Of 642 adults with type...

  5. Effect of re-coaching on self-injection of insulin in older diabetic patients - Impact of cognitive impairment.

    Science.gov (United States)

    Omori, Keiko; Kawamura, Takahiko; Urata, Misako; Matsuura, Mayumi; Kusama, Minoru; Imamine, Rui; Watarai, Atsuko; Nakashima, Eitaro; Umemura, Toshitaka; Hotta, Nigishi

    2017-08-01

    We investigated the effect of re-coaching on self-injection of insulin and impact of cognitive function in 100 older diabetic patients. We examined patients on a variety of skills and knowledge regarding self-injection of insulin and evaluated the effect of re-coaching the patients after 3months and 4years. We also investigated the influence of cognitive impairment (CI) on coaching. Skills scores for self-injection of insulin and HbA1c improved significantly 3months after re-coaching. In 51 patients followed-up for 4years, skills scores were maintained during the 4years, while knowledge scores improved after 3months but then returned to the baseline level. In the group of patients with CI as determined by the Mini-Mental Status Examination, skills scores were similar to those in the group without CI, while knowledge scores were significantly lower as compared with those in the group without CI at any time point. Skills scores were maintained during the 4years regardless of CI. The present study showed that re-coaching in skills for self-injection of insulin was effective in improving and maintaining insulin treatment in older diabetic patients, even if patients had CI. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effects of Sleep Deprivation on Hypoglycemia-Induced Cognitive Impairment and Recovery in Adults With Type 1 Diabetes.

    Science.gov (United States)

    Inkster, Berit E; Zammitt, Nicola N; Ritchie, Stuart J; Deary, Ian J; Morrison, Ian; Frier, Brian M

    2016-05-01

    To ascertain whether hypoglycemia in association with sleep deprivation causes greater cognitive dysfunction than hypoglycemia alone and protracts cognitive recovery after normoglycemia is restored. Fourteen adults with type 1 diabetes underwent a hyperinsulinemic, hypoglycemic clamp on two separate occasions. Before one glucose clamp, the participants stayed awake overnight to induce sleep deprivation. Participants were randomized and counterbalanced to the experimental condition. Cognitive function tests were performed before and during hypoglycemia and for 90 min after restoration of normoglycemia. Cognitive impairment during hypoglycemia did not differ significantly between the sleep-deprived and non-sleep-deprived conditions. However, in the sleep-deprived state, digit symbol substitution scores and choice reaction times were significantly poorer during recovery (P sleep deprivation, such as tiredness, were removed. Hypoglycemia per se produced a significant decrement in cognitive function; coexisting sleep deprivation did not have an additive effect. However, after restoration of normoglycemia, preceding sleep deprivation was associated with persistence of hypoglycemic symptoms and greater and more prolonged cognitive dysfunction during the recovery period. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus: The Hoorn Study.

    Science.gov (United States)

    Adriaanse, M C; Dekker, J M; Heine, R J; Snoek, F J; Beekman, A J; Stehouwer, C D; Bouter, L M; Nijpels, G; Pouwer, F

    2008-07-01

    To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). Cross-sectional data from a population-based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score > or = 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels. The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P women with IGM [odds ratio (OR) = 3.60, 95% confidence interval (CI) = 1.57 to 8.28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non-significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms reduced the strength of these associations. Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could be intermediate factors.

  8. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    Directory of Open Access Journals (Sweden)

    Cen Fu

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD, micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD, cortical volumetric BMD (vBMD and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV, trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC, bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  9. Potential contribution of diabetes mellitus to orthostatic blood pressure fall and conversion of mild cognitive impairment to dementia

    Directory of Open Access Journals (Sweden)

    Muratli S

    2016-01-01

    Full Text Available Sevilay Muratli,1 Fatih Tufan,1 Ozlem Soyluk,2 Gulistan Bahat,1 Mehmet Akif Karan1 1Department of Geriatrics, 2Department of Endocrinology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, TurkeyWe read the article “Orthostatic blood pressure in people with mild cognitive impairment predicts conversion to dementia” by Hayakawa et al1 with interest. It is well-known that many individuals with mild cognitive impairment (MCI progress to dementia.2 However, we do not exactly know which risk factors increase this risk and to what extent. Hypertension is a risk factor for Alzheimer’s disease and vascular dementia. However, the findings of this study make us consider hypotension as a new risk factor for dementia. Furthermore, a recently published 6-year prospective general population cohort study suggested that not only orthostatic hypotension (OH, but also symptoms of OH seemed to be risk factors for cognitive decline.3 Notably, in the study by Elmstahl et al3, hypertension and diabetes mellitus (DM were more common in subjects with dementia. We would like to make some comments on this well-designed study.

  10. Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

    Science.gov (United States)

    Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

    2015-01-01

    Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

  11. Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients.

    Science.gov (United States)

    Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

    2017-02-28

    People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghrelin levels compared with their healthy-cognition subjects (all p ghrelin level was one of independent factors for MCI in T2DM patients (p ghrelin levels were positively associated with the scores of Montreal Cognitive Assessment (r = 0.196, p = 0.041) and Auditory Verbal Learning Test-delayed recall (r = 0.197, p = 0.040) after adjustment for HbA1c, FBG and HOMA-IR, wherein the latter represented episodic memory functions. No significant differences were found for the distributions of genotype and allele of ghrelin rs4684677 polymorphism between MCI and control group. A total of 218 T2DM patients, with 112 patients who satisfied the MCI diagnostic criteria and 106 who exhibited healthy cognition, were enrolled in this study. Demographic characteristics, clinical variables and cognitive performances were extensively assessed. Plasma ghrelin levels and ghrelin rs4684677 polymorphism were also determined. Our results suggest that decreased ghrelin levels are associated with MCI, especially with episodic memory dysfunction in T2DM populations.

  12. Nontraumatic fracture risk with diabetes mellitus and impaired fasting glucose in older white and black adults: the health, aging, and body composition study.

    Science.gov (United States)

    Strotmeyer, Elsa S; Cauley, Jane A; Schwartz, Ann V; Nevitt, Michael C; Resnick, Helaine E; Bauer, Douglas C; Tylavsky, Frances A; de Rekeneire, Nathalie; Harris, Tamara B; Newman, Anne B

    2005-07-25

    Diabetes mellitus (DM) and related complications may increase clinical fracture risk in older adults. Our objectives were to determine if type 2 diabetes mellitus or impaired fasting glucose was associated with higher fracture rates in older adults and to evaluate how diabetic individuals with fractures differed from those without fractures. The Health, Aging, and Body Composition Study participants were well-functioning, community-dwelling men and women aged 70 to 79 years (N = 2979; 42% black), of whom 19% had DM and 6% had impaired fasting glucose at baseline. Incident nontraumatic clinical fractures were verified by radiology reports for a mean +/- SD of 4.5 +/- 1.1 years. Cox proportional hazards regression models determined how DM and impaired fasting glucose affected subsequent risk of fracture. Diabetes mellitus was associated with elevated fracture risk (relative risk, 1.64; 95% confidence interval, 1.07-2.51) after adjustment for a hip bone mineral density (BMD) and fracture risk factors. Impaired fasting glucose was not significantly associated with fractures (relative risk, 1.34; 95% confidence interval, 0.67-2.67). Diabetic participants with fractures had lower hip BMD (0.818 g/cm(2) vs 0.967 g/cm(2); Pbattery score (5.0 vs 7.0), and falls (37% vs 21%) compared with diabetic participants without fractures (P<.05). These results indicate that older white and black adults with DM are at higher fracture risk compared with nondiabetic adults with a similar BMD since a higher risk of nontraumatic fractures was found after adjustment for hip BMD. Fracture prevention needs to target specific risk factors found in older adults with DM.

  13. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus and associated risk factors among adults living in a rural Koladiba town, northwest Ethiopia.

    Science.gov (United States)

    Worede, Abebaw; Alemu, Shitaye; Gelaw, Yalemzewod Assefa; Abebe, Molla

    2017-07-06

    Diabetes mellitus is becoming a big public health challenge, particularly in developing countries like Ethiopia. It is a manageable disease if early screening and follow up is made. However, as studies in Ethiopia are limited and unorganized, determining the magnitude of prediabetes and diabetes and identifying associated risk factors is quite essential. A community-based, cross-sectional study was conducted from February to April 2015 among adults (aged ≥20 years) in a rural Koladiba town. A multistage sampling technique was used to select a total of 392 study participants. Data were collected after a fully informed written consent was obtained from each participant. Demographic, behavioral, and clinical data were collected using a well-structured questionnaire. Multivariable logistic regression models were fitted to control the effect of confounders. Adjusted odds ratios (AOR) with their 95% confidence intervals (95% CI) were computed to measure associations. A p value of fasting glucose and undiagnosed diabetes mellitus were 12% (95% CI 9-16) and 2.3% (95% CI 1.1-4), respectively, in Koladiba. Overweight (AOR: 4.257, 95% CI 1.345-13.476), obesity (AOR: 5.26, 95% CI 1.138-24.316), hypertriglyceridemia (AOR: 2.83, 95% CI 1.451-5.521), and systolic hypertension (AOR: 3.858, 95% CI 1.62-9.189) were found to be independently associated with impaired fasting glucose. Positive family history of diabetes also showed a marginal association with impaired fasting glucose (p = 0.057). Male sex (p = 0.012) and hypertriglyceridemia (p = 0.030) were associated with undiagnosed diabetes mellitus. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus are found to be significant. Obesity, hypertriglyceridemia, and systolic hypertension are independently associated with impaired fasting glucose among adults. We recommend that the community be aware of healthy life style, early screening, and maintain continuous follow up.

  14. Progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screening programme in general practice: the ADDITION Study, Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Signe Sætre; Glümer, Charlotte; Sandbæk, Annelli

    2007-01-01

    -examination after 1 year. Glucose tolerance classification was based on the 1999 WHO definition. At follow-up, diabetes was based on one diabetic glucose value of fasting blood glucose or 2-h blood glucose. RESULTS: At baseline, 308 persons had IFG and 503 had IGT. The incidence of diabetes was 17.6 and 18.8 per...

  15. Type 2 diabetes impairs odour detection, olfactory memory and olfactory neuroplasticity; effects partly reversed by the DPP-4 inhibitor Linagliptin.

    Science.gov (United States)

    Lietzau, Grazyna; Davidsson, William; Östenson, Claes-Göran; Chiazza, Fausto; Nathanson, David; Pintana, Hiranya; Skogsberg, Josefin; Klein, Thomas; Nyström, Thomas; Darsalia, Vladimer; Patrone, Cesare

    2018-02-23

    Recent data suggest that olfactory deficits could represent an early marker and a pathogenic mechanism at the basis of cognitive decline in type 2 diabetes (T2D). However, research is needed to further characterize olfactory deficits in diabetes, their relation to cognitive decline and underlying mechanisms.The aim of this study was to determine whether T2D impairs odour detection, olfactory memory as well as neuroplasticity in two major brain areas responsible for olfaction and odour coding: the main olfactory bulb (MOB) and the piriform cortex (PC), respectively. Dipeptidyl peptidase-4 inhibitors (DPP-4i) are clinically used T2D drugs exerting also beneficial effects in the brain. Therefore, we aimed to determine whether DPP-4i could reverse the potentially detrimental effects of T2D on the olfactory system.Non-diabetic Wistar and T2D Goto-Kakizaki rats, untreated or treated for 16 weeks with the DPP-4i linagliptin, were employed. Odour detection and olfactory memory were assessed by using the block, the habituation-dishabituation and the buried pellet tests. We assessed neuroplasticity in the MOB by quantifying adult neurogenesis and GABAergic inhibitory interneurons positive for calbindin, parvalbumin and carletinin. In the PC, neuroplasticity was assessed by quantifying the same populations of interneurons and a newly identified form of olfactory neuroplasticity mediated by post-mitotic doublecortin (DCX) + immature neurons.We show that T2D dramatically reduced odour detection and olfactory memory. Moreover, T2D decreased neurogenesis in the MOB, impaired the differentiation of DCX+ immature neurons in the PC and altered GABAergic interneurons protein expression in both olfactory areas. DPP-4i did not improve odour detection and olfactory memory. However, it normalized T2D-induced effects on neuroplasticity.The results provide new knowledge on the detrimental effects of T2D on the olfactory system. This knowledge could constitute essentials for

  16. Anion Gap Toxicity in Alloxan Induced Type 2 Diabetic Rats Treated with Antidiabetic Noncytotoxic Bioactive Compounds of Ethanolic Extract of Moringa oleifera

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    Maxwell Omabe

    2014-01-01

    Full Text Available Moringa oleifera (MO is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P=0.0698; there was no gain in weight between the MO treated and the control groups (P>0.8115. However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P<0.0001, and more than twofold increase in anion gap (P<0.0001; metformin treatment also decreased bicarbonate (P<0.0001 and resulted in a threefold increase in anion gap (P<0.0001. Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats.

  17. Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

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    Rayees Ahmad Wani

    2015-01-01

    Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

  18. Exocrine dysfunction correlates with endocrinal impairment of pancreas in Type 2 diabetes mellitus

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    H R Prasanna Kumar

    2018-01-01

    Full Text Available Background: Diabetes mellitus (DM is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1 is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. Aim: The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. Methodology: A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics. Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t-test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Results: Statistically nonsignificant (P = 0.5051 relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation (P = 0.003 between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy (P = 0.001 and peripheral pulses (P = 0.001 with FE-1 levels were found to be statistically significant. Conclusion: This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  19. Exocrine Dysfunction Correlates with Endocrinal Impairment of Pancreas in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Prasanna Kumar, H R; Gowdappa, H Basavana; Hosmani, Tejashwi; Urs, Tejashri

    2018-01-01

    Diabetes mellitus (DM) is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1) is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM) by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics). Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t -test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Statistically nonsignificant ( P = 0.5051) relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation ( P = 0.003) between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy ( P = 0.001) and peripheral pulses ( P = 0.001) with FE-1 levels were found to be statistically significant. This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  20. [Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation].

    Science.gov (United States)

    Xu, Tao; Shi, Me; Qiu, Yun-Xia; Wang, Yan-Gang

    2014-06-01

    To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA

  1. A1C predicts type 2 diabetes and impaired glucose tolerance in a population at risk: the community diabetes prevention project

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    Leite Silmara AO

    2009-09-01

    Full Text Available Abstract Aims In a population at risk for type 2 diabetes (T2DM, we assessed early physical and metabolic markers that predict progression from normal to impaired glucose tolerance (IGT and T2DM. Methods A total of 388 individuals (22% male, age 46 + 11 years at risk for T2DM were randomized to Standard (n = 182 or Intervention (n = 206 care and evaluated at baseline and 5 annual follow-up visits, including blood pressure, BMI, A1C, lipids, urine albumin/creatinine ratio, VO2max, fasting glucose, insulin and C-peptide. The Standard group received results of annual lab tests and quarterly newsletters, while the Intervention group received quarterly newsletters and detailed discussions of lab results, routine self-directed activities, semi-annual group meetings and monthly telephone calls for ongoing support. Results Overall, 359 (93% returned for at least one follow-up visit and 272 (70% completed the final 5-year assessment. Return rates, changes in measures and incidence of IGT/T2DM were similar between groups. Low cardiorespiratory fitness (VO2max was the most prevalent baseline abnormality. A1C and BMI were significant predictors of IGT/T2DM after controlling for other factors. The risk of IGT/T2DM within 5 years was 17.16 (95% CL: 6.169, 47.736 times greater for those with baseline A1C>=5.8% as compared to those Conclusion Baseline A1C>=5.8% was a significant predictor of IGT/T2DM within 5 years in a population at high risk for T2DM. A1C is routinely performed among patients with diabetes, however these data and other evidence suggest that it may also be a useful tool for risk assessment and screening.

  2. Pharmacist managed diabetes and cardiovascular risk reduction clinic in kidney transplant recipients: bridging the gap in care transition.

    Science.gov (United States)

    Pinelli, Nicole R; Clark, Lindsey M; Carrington, Anne C; Carrington, Julia L; Malinzak, Lauren; Patel, Anita

    2014-12-01

    The purpose was to assess the feasibility of a care transition intervention for kidney transplant recipients (KTRs) with diabetes. Results document improved quality indicators and reduced resource utilization. These findings imply that a care transition intervention for KTRs with diabetes is feasible and associated with improved patient outcomes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    and serum in participants with neuropathy than in those without neuropathy [cerebrospinal fluid: median (range) 131 (86-173) vs 101 (70-190) μg/l, P = 0.08 and serum: 3725 (920-7060) vs 2220 (1130-4780), P = 0.06). CONCLUSIONS: Cerebrospinal fluid soluble CD163 level is associated with impaired peripheral......AIMS: To measure soluble CD163 levels in the cerebrospinal fluid and serum of people with Type 2 diabetes, with and without polyneuropathy, and to relate the findings to peripheral nerve function. METHODS: A total of 22 people with Type 2 diabetes and 12 control subjects without diabetes were...... included in this case-control study. Participants with diabetes were divided into those with neuropathy (n = 8) and those without neuropathy (n = 14) based on clinical examination, vibratory perception thresholds and nerve conduction studies. Serum and cerebrospinal fluid soluble CD163 levels were analysed...

  4. Caspase-14 Expression Impairs Retinal Pigment Epithelium Barrier Function: Potential Role in Diabetic Macular Edema

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    Selina Beasley

    2014-01-01

    Full Text Available We recently showed that caspase-14 is a novel molecule in retina with potential role in accelerated vascular cell death during diabetic retinopathy (DR. Here, we evaluated whether caspase-14 is implicated in retinal pigment epithelial cells (RPE dysfunction under hyperglycemia. The impact of high glucose (HG, 30 mM D-glucose on caspase-14 expression in human RPE (ARPE-19 cells was tested, which showed significant increase in caspase-14 expression compared with normal glucose (5 mM D-glucose + 25 mM L-glucose. We also evaluated the impact of modulating caspase-14 expression on RPE cells barrier function, phagocytosis, and activation of other caspases using ARPE-19 cells transfected with caspase-14 plasmid or caspase-14 siRNA. We used FITC-dextran flux assay and electric cell substrate impedance sensing (ECIS to test the changes in RPE cell barrier function. Similar to HG, caspase-14 expression in ARPE-19 cells increased FITC-dextran leakage through the confluent monolayer and decreased the transcellular electrical resistance (TER. These effects of HG were prevented by caspase-14 knockdown. Furthermore, caspase-14 knockdown prevented the HG-induced activation of caspase-1 and caspase-9, the only activated caspases by HG. Phagocytic activity was unaffected by caspase-14 expression. Our results suggest that caspase-14 contributes to RPE cell barrier disruption under hyperglycemic conditions and thus plays a role in the development of diabetic macular edema.

  5. Impaired fat oxidation after a single high-fat meal in insulin-sensitive nondiabetic individuals with a family history of type 2 diabetes.

    Science.gov (United States)

    Heilbronn, Leonie K; Gregersen, Søren; Shirkhedkar, Deepali; Hu, Dachun; Campbell, Lesley V

    2007-08-01

    Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P FAT)/CD36 (P fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1alpha and FAT/CD36 are likely candidates in mediating this response.

  6. Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

    Science.gov (United States)

    Cao, Bing; Rosenblat, Joshua D; Brietzke, Elisa; Park, Caroline; Lee, Yena; Musial, Natalie; Pan, Zihang; Mansur, Rodrigo B; McIntyre, Roger S

    2018-05-23

    The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Bushen Huoxue Attenuates Diabetes-Induced Cognitive Impairment by Improvement of Cerebral Microcirculation: Involvement of RhoA/ROCK/moesin and Src Signaling Pathways

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    Yuan Li

    2018-05-01

    Full Text Available Type 2 Diabetes mellitus (T2DM is closely correlated with cognitive impairment and neurodegenerative disease. Bushen Huoxue (BSHX is a compound Chinese medicine used clinically to treat diabetes-induced cognitive impairment. However, its underlying mechanisms remain unclear. In the present study, KKAy mice, a genetic model of type 2 diabetes with obesity and insulin resistant hyperglycemia, received a daily administration of BSHX for 12 weeks. Blood glucose was measured every 4 weeks. After 12 weeks, BSHX treatment significantly ameliorated the T2DM related insults, including the increased blood glucose, the impaired spatial memory, decreased cerebral blood flow (CBF, occurrence of albumin leakage, leukocyte adhesion and opening capillary rarefaction. Meanwhile, the downregulation of the tight junction proteins (TJ claudin-5, occludin, zonula occluden-1 (ZO-1 and JAM-1 between endothelial cells, amyloid-β (Aβ accumulation in hippocampus, increased AGEs and RAGE, and expression of RhoA/ROCK/moesin signaling pathway and phosphorylation of Src kinase in KKAy mice were significantly protected by BSHX treatment. These results indicate that the protective effect of BSHX on T2DM-induced cognitive impairment involves regulation of RhoA/ROCK1/moesin signaling pathway and phosphorylation of Src kinase.

  8. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    Science.gov (United States)

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  9. Impairments to Vision

    Science.gov (United States)

    ... an external Non-Government web site. Impairments to Vision Normal Vision Diabetic Retinopathy Age-related Macular Degeneration In this ... pictures, fixate on the nose to simulate the vision loss. In diabetic retinopathy, the blood vessels in ...

  10. Perfil de risco cardíaco no diabetes mellitus e na glicemia de jejum alterada Cardiac risk profile in diabetes mellitus and impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    Beatriz D'Agord Schaan

    2004-08-01

    population-based cross-sectional study was carried out in a representative random cluster sampling of 1,066 adult urban population (>20 years in the state of Rio Grande do Sul between 1999 and 2000. A structured questionnaire on coronary risk factors was applied and sociodemographic characteristics of all adults older than 20 years living in the same dwelling were collected. Subjects were clinically evaluated and blood samples were obtained for measuring total cholesterol and fasting glycemia. Statistical analysis was performed using Stata 7 and a 5% significance level was set. Categorical variables were compared by Pearson's chi-square and continuous variables were compared using Student's t-test or Anova and multivariate analysis, all controlled for the cluster effect. RESULTS: Of 992 subjects, 12.4% were diabetic and 7.4% had impaired fasting glucose. Among the risk factors evaluated, subjects who presented any kind of glucose homeostasis abnormality were at a higher prevalence of obesity (17.8, 29.2 and 35.3% in healthy subjects, impaired fasting glucose and DM respectively, p<0.001, hypertension (30.1, 56.3 and 50.5% in healthy subjects, impaired fasting glucose and DM, respectively, p<0.001, and hypercholesterolemia (23.2, 35.1 and 39.5 in healthy subjects, impaired fasting glucose and DM respectively, p=0.01. CONCLUSION: Subjects with any kind of glucose homeostasis abnormality represent a group, which preventive individual and population health policies should target since they have higher prevalence of coronary artery disease risk factors.

  11. Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats.

    Science.gov (United States)

    Kim, Young Hoon; Sung, Yun-Hee; Lee, Hee-Hyuk; Ko, Il-Gyu; Kim, Sung-Eun; Shin, Mal-Soon; Kim, Bo-Kyun

    2014-08-01

    During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.

  12. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

    Science.gov (United States)

    Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

    2013-12-09

    To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

  13. Consumption of dairy foods in relation to impaired glucose metabolism and type 2 diabetes mellitus: the Maastricht Study.

    Science.gov (United States)

    Eussen, Simone J P M; van Dongen, Martien C J M; Wijckmans, Nicole; den Biggelaar, Louise; Oude Elferink, Stefanie J W H; Singh-Povel, Cécile M; Schram, Miranda T; Sep, Simone J S; van der Kallen, Carla J; Koster, Annemarie; Schaper, Nicolaas; Henry, Ronald M A; Stehouwer, Coen D A; Dagnelie, Pieter C

    2016-04-01

    Observational studies suggest an inverse association between total dairy product intake and diabetes risk. However, there is a lack of information on the relationship of specific dairy products with impaired glucose metabolism (IGM) and type 2 diabetes mellitus (T2DM). Individuals aged 40-75 years were recruited for the Maastricht Study. All the participants filled out a 253-food item FFQ, covering fifty specific dairy items that captured differences between full-fat, semi-skimmed and skimmed products, as well as fermented and non-fermented products. Glucose metabolism status was assessed by an oral glucose tolerance test, and participants were informed on their glucose metabolism status after returning the FFQ. Data of 2391 individuals were available to estimate OR (95 % CI) for IGM (n 470) and newly diagnosed (ND) T2DM (n 125), with adjustment for age, sex, BMI, physical activity, smoking status, education, energy intake and intakes of vegetables, fruits, meat and fish. For IGM, fully adjusted analyses revealed inverse associations, with OR comparing the highest with the lowest tertile of intake of 0·73 (95 % CI 0·55, 0·96) for skimmed products and 0·74 (95 % CI 0·54, 0·99) for fermented products. These dairy products were not associated with ND T2DM. In contrast, full-fat products were positively associated with ND T2DM (OR 2·01; 95 % CI 1·16, 3·47), whereas total dairy product intake was inversely associated with ND T2DM (OR 0·50; 95 % CI 0·26, 0·93). In conclusion, individuals with a high consumption of skimmed and fermented products had lower odds of having IGM, and individuals with a high consumption of total dairy products had lower odds of having ND T2DM. High intake of full-fat products was not related to IGM but was positively related to ND T2DM.

  14. Prevalence of impaired fasting glucose and type 1 and 2 diabetes mellitus in a large nationwide working population in Spain.

    Science.gov (United States)

    Reviriego, Jesús; Vázquez, Luis Alberto; Goday, Albert; Cabrera, Martha; García-Margallo, María Teresa; Calvo, Eva

    2016-04-01

    To report the prevalence of impaired fasting glucose (IFG), undiagnosed and diagnosed diabetes, and their association to occupational categories in a representative sample of working population in Spain. A cross-sectional study of workers who attended routine medical check-ups from January 2007 to December 2007. A structured questionnaire was completed, and physical examinations and routine serum biochemical tests were performed. IFG was defined as fasting glucose levels ranging from 100 to 125 mg/dl with no diagnosis of T1DM or T2DM; T1DM was defined as previous diagnosis of T1DM; and T2DM as previous diagnosis of T2DM, treatment with oral antidiabetic drugs or insulin or fasting glucose levels ≥126 mg/dl, according to ADA criteria. Of the 371,997 participants (median age 35 [interquartile range 29-44] years), 72.4% were male. Raw prevalence rates (95% CI) of IFG, undiagnosed (UKDM), and previously known type 2 (KDM2) and type 1 (KDM1) diabetes were 10.4% (10.3-10.5%), 1.3% (1.2-1.3%), 1.1% (1.1-1.2%), and 0.3% (0.3-0.3%), respectively. With the exception of KDM1, prevalence of these conditions increased with age and was greater among manual/blue-collar workers (12.1%, 1.5%, 1.3% and 0.3%, respectively) as compared to non-manual/white-collar workers (7.3%, 0.8%, 0.8% and 0.3%, respectively). Age- and sex-adjusted prevalence rates of IFG, UKDM and KDM2 were 13.1%, 2.0% and 2.4%, respectively. In this sample of Spanish working population, impaired glycemic profiles were common. Prevalence rates of IFG and T2DM were high among blue-collar workers (except for T1DM). These data emphasize the need for earlier structured preventive schemes. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  15. Type 2 diabetes mellitus might be a risk factor for mild cognitive impairment progressing to Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Li W

    2016-09-01

    Full Text Available Wei Li,1,2 Tao Wang,1,2 Shifu Xiao1,2 1Alzheimer’s Disease and Related Disorders Center, 2Department of Geriatric Psychiatry, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China Background: Mild cognitive impairment (MCI is the prodromal stage of Alzheimer’s disease (AD, so identification of the related risk factors can be helpful. Although the association between type 2 diabetes mellitus (T2DM and these modest changes in cognition is well established, whether T2DM will promote the transformation of MCI into AD is not a unified conclusion.Objective: This study aims to explore the relationship between T2DM and MCI in the elderly population living in the community in Shanghai, People’s Republic of China.Methods: A total of 197 participants were included in the study. They were screened for T2DM, hyperlipidemia, traumatic brain injury, and family history of dementia. The Mini-Mental State Examination and the Montreal Cognitive Assessment were used to assess cognitive function. The diagnosis of AD was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, whereas the diagnosis of MCI was made according to Petersen’s criteria. Then, we investigated the relation between T2DM and MCI.Results: A total of 82 (41.6% participants had no cognitive impairment, 82 (41.6% participants had MCI, and 33 (16.8% participants had AD. Multivariate logistic regression models demonstrated that T2DM was a risk factor for AD (odds ratio =49.723, 95% CI =21.173–111.987.Conclusion: T2DM might be a risk factor for MCI progressing into AD. Keywords: T2DM, AD, MCI, risk factor

  16. Metabolic syndrome components and diabetes incidence according to the presence or absence of impaired fasting glucose: The Japan Epidemiology Collaboration on Occupational Health Study.

    Science.gov (United States)

    Kurotani, Kayo; Miyamoto, Toshiaki; Kochi, Takeshi; Eguchi, Masafumi; Imai, Teppei; Nishihara, Akiko; Tomita, Kentaro; Uehara, Akihiko; Yamamoto, Makoto; Murakami, Taizo; Shimizu, Chii; Shimizu, Makiko; Nagahama, Satsue; Nakagawa, Tohru; Honda, Toru; Yamamoto, Shuichiro; Okazaki, Hiroko; Sasaki, Naoko; Hori, Ai; Nishiura, Chihiro; Kuwahara, Keisuke; Kuroda, Reiko; Akter, Shamima; Kashino, Ikuko; Nanri, Akiko; Kabe, Isamu; Mizoue, Tetsuya; Kunugita, Naoki; Dohi, Seitaro

    2017-09-01

    We prospectively examined the association of diabetes risk with the number of metabolic abnormalities, as well as their combinations, according to the presence or absence of impaired fasting glucose (IFG) in a large-scale Japanese working population. Participants included 55,271 workers at 11 companies who received periodic health check-ups between 2008 and 2013. The metabolic syndrome (MetS) components were defined using the 2009 Joint Interim Statement. IFG was defined as fasting plasma glucose 5.6-6.9 mmol/L. Diabetes newly diagnosed after the baseline examination was defined according to the American Diabetes Association criteria. We calculated the hazard ratios (HRs) for diabetes incidence using the Cox proportional hazards model. During the follow-up period (median 4.95 years), 3183 subjects developed diabetes. In individuals with normal fasting glucose levels, the risk of diabetes increased steadily with the increasing number of MetS components; the multivariable-adjusted HRs for incident diabetes for the number of MetS components were 2.0, 4.3, 7.0, and 10.0 for one, two, three, or four MetS components, respectively, compared with the absence of components. A similar association was observed among individuals with IFG; the corresponding HRs were 17.6, 23.8, 33.9, and 40.7. The combinations that included central obesity appeared to be more strongly associated with diabetes risk than other combinations with the same number of MetS components within the same glucose status. Our findings indicate that risk stratification of individuals by the presence or absence of IFG and the number of MetS components can detect individuals with a high risk of diabetes. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  17. [Prevalence of diabetes and impaired glucose regulation in Chengdu populations and associated dietary risk factors].

    Science.gov (United States)

    Dai, Hua; Chen, Li-Yu; Li, Shuang-Qing

    2014-01-01

    To determine the prevalence of type 2 DM and impaired glucose regulation (IGR) in Chengdu populations and to identify dietary risk factors associated with DM and IGR. Two communities in Chengdu were selected for this study. Fasting blood-glucose (FBG) and 2-hour post-meal blood glucose (2 hGlu) tests were performed in the community residents. The participants were asked to complete a questionair recording their daily food intaking. The total calorie of food, percentage of different kinds of food, and intake of electrolyte, vietamine and micro minerals were calculated and compared between those with and without type 2 DM or IGR. Of the study participants, 18.59% had type 2 DM and 24.22% had IGR. Those with DM had higher levels of intake of calorie,fat,protein and sodium, and lower levels of intake of cellulose, carbohydrates, Iron, zinc, selenium,manganese and vietamine C and E compared with those without DM/IGR (P vitamine C and E compared with those without DM/IGR (P Vitamine E was identified as a protective factor of type 2 DM (OR = 0.733) and IGR (OR = 0.990). Chengdu has a higher than national average prevalence of type 2 DM and IGR. The high percentage of dietary fat and low levels of Vitamine E are major risk factors of type 2 DM and IGR.

  18. Reversal of diuretic-associated impaired glucose tolerance and new-onset diabetes: results of the STAR-LET study.

    Science.gov (United States)

    Bakris, George; Molitch, Mark; Zhou, Qian; Sarafidis, Pantelis; Champion, Annette; Bacher, Peter; Sowers, James R

    2008-01-01

    Reversal of new-onset diabetes secondary to thiazide diuretic use remains questionable. STAR-LET was a 6-month extension of the Study of Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the effects of a fixed-dose renin-angiotensin system inhibitor (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/-2.3; P<.001). This exploratory study suggests that the impairment in glycemic control seen with use of a thiazide diuretic combined with a RASI can be reversed by switching to a regimen that does not include a diuretic.

  19. Impairment of the vascular relaxation and differential expression of caveolin-1 of the aorta of diabetic +db/+db mice.

    Science.gov (United States)

    Lam, Tze Yan; Seto, Sai Wang; Lau, Yee Man; Au, Lai Shan; Kwan, Yiu Wa; Ngai, Sai Ming; Tsui, Kwong Wing

    2006-09-28

    In this study, we compared the endothelium-dependent and -independent relaxation of the isolated thoracic aorta of control (+db/+m) and diabetic (+db/+db) (C57BL/KsJ) mice. The gene expression (mRNA and protein) level of the muscarinic M(3) receptors, endothelial nitric oxide synthase (eNOS) and caveolin-1 of the aorta was also evaluated. Acetylcholine caused a concentration-dependent, N(G)-nitro-L-arginine methyl-ester (20 microM)-sensitive relaxation, with approximately 100% relaxation at 10 microM, in +db/+m mice. In +db/+db mice, the acetylcholine-induced relaxation was significantly smaller (maximum relaxation: approximately 80%). The sodium nitroprusside-mediated relaxation was slightly diminished in +db/+db mice, compared to +db/+m mice. However, there was no significant difference in the isoprenaline- and cromakalim-induced relaxation observed in both species. The mRNA and protein expression levels of caveolin-1 were significantly higher in the aorta of +db/+db mice. In contrast, there was no difference in the mRNA and protein expression levels of eNOS and muscarinic M(3) receptors between these mice. Our results demonstrate that the impairment of the acetylcholine-induced, endothelium-dependent aortic relaxation observed in +db/+db mice was probably associated with an enhanced expression of caveolin-1 mRNA and protein.

  20. Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005-2011.

    Science.gov (United States)

    Esteghamati, Alireza; Etemad, Koorosh; Koohpayehzadeh, Jalil; Abbasi, Mehrshad; Meysamie, Alipasha; Noshad, Sina; Asgari, Fereshteh; Mousavizadeh, Mostafa; Rafei, Ali; Khajeh, Elias; Neishaboury, Mohamadreza; Sheikhbahaei, Sara; Nakhjavani, Manouchehr

    2014-02-01

    To estimate the prevalence and trends of diabetes mellitus (DM) and impaired fasting glucose (IFG), 2005-2011, and to determine the contribution of obesity to DM prevalence. Data from Surveillance of Risk Factors of Non-communicable Diseases (SuRFNCD) conducted in 2005, 2007, and 2011 were gathered. DM was defined as presence of self-reported previous diagnosis or a fasting plasma glucose (FPG)≥7 mmol/L. IFG was diagnosed with FPG levels between 5.6 and 6.9 mmol/L. Prevalence rates for 2011 and trends for 2005-2011 were determined by extrapolating survey results to Iran's adult population. Population attributable fraction (PAF) of obesity was also calculated. In 2011, IFG and total DM prevalence rates were 14.60% (95%CI: 12.41-16.78) and 11.37% (95%CI: 9.86-12.89) among 25-70 years, respectively. DM was more common in older age (p obesity (BMI≥30 kg/m(2)), and central obesity (waist circumference≥90 cm), respectively. Additionally, the DM increase rate in 2005-2011, was 20 times higher in morbidly obese compared with lean individuals. More than four million Iranian adults have DM which has increased by 35% over the past seven years, owing in large part, to expanding obesity epidemic. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism

    Directory of Open Access Journals (Sweden)

    Hameed Shihab

    2012-06-01

    Full Text Available Abstract Background/Aims Infants with diabetes insipidus (DI, especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. Methods A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose. The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott. We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. Results After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L vs. only 51% on the old regimen (p = 0.0001. The sodium ranged from 132-154 mmol/L, compared to 120–156 on the old regimen. She was discharged home. Conclusion This practical regimen improved sodium control, parental independence, and allowed discharge home.

  2. Home blood sodium monitoring, sliding-scale fluid prescription and subcutaneous DDAVP for infantile diabetes insipidus with impaired thirst mechanism.

    Science.gov (United States)

    Hameed, Shihab; Mendoza-Cruz, Abel C; Neville, Kristen A; Woodhead, Helen J; Walker, Jan L; Verge, Charles F

    2012-06-09

    Infants with diabetes insipidus (DI), especially those with impaired thirst mechanism or hypothalamic hyperphagia, are prone to severe sodium fluctuations, often requiring hospitalization. We aimed to avoid dangerous fluctuations in serum sodium and improve parental independence. A 16-month old girl with central DI, absent thirst mechanism and hyperphagia following surgery for hypothalamic astrocytoma had erratic absorption of oral DDAVP during chemotherapy cycles. She required prolonged hospitalizations for hypernatremia and hyponatremic seizure. Intensive monitoring of fluid balance, weight and clinical assessment of hydration were not helpful in predicting serum sodium. Discharge home was deemed unsafe. Oral DDAVP was switched to subcutaneous (twice-daily injections, starting with 0.01mcg/dose, increasing to 0.024mcg/dose). The parents adjusted daily fluid allocation by sliding-scale, according to the blood sodium level (measured by handheld i-STAT analyser, Abbott). We adjusted the DDAVP dose if fluid allocation differed from maintenance requirements for 3 consecutive days. After 2.5 months, sodium was better controlled, with 84% of levels within reference range (135-145 mmol/L) vs. only 51% on the old regimen (p = 0.0001). The sodium ranged from 132-154 mmol/L, compared to 120-156 on the old regimen. She was discharged home. This practical regimen improved sodium control, parental independence, and allowed discharge home.

  3. Effect of the treatment of Type 2 diabetes mellitus on the development of cognitive impairment and dementia.

    Science.gov (United States)

    Areosa Sastre, Almudena; Vernooij, Robin Wm; González-Colaço Harmand, Magali; Martínez, Gabriel

    2017-06-15

    Prevention of cognitive impairment and dementia is an important public health goal. Epidemiological evidence shows a relationship between cognitive impairment and Type 2 diabetes mellitus. The risk of dementia increases with duration of disease. This updated systematic review investigated the effect on cognitive function of the type of treatment and level of metabolic control in people with Type 2 diabetes. To assess the effects of different strategies for managing Type 2 diabetes mellitus on cognitive function and the incidence of dementia. We searched ALOIS (the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG)), the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL and LILACS on 15 October 2016. ALOIS contains records from all major health care databases, (CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many trials' registers and grey literature sources. We included randomised controlled trials (RCTs) which compared two or more different treatments for Type 2 diabetes mellitus and in which cognitive function was measured at baseline and after treatment. Two review authors independently extracted data and assessed the quality of the included RCTs. We pooled data for comparable trials and estimated the effects of treatment by using risk ratios (RRs) and mean differences (MDs), according to the nature of the outcome. We assessed the quality of the evidence using GRADE methods. We identified seven eligible studies but only four provided data we could include in efficacy analyses. Two of these studies compared intensive versus standard glycaemic control and two compared different pharmacological treatments. All studies were at unclear risk of bias in at least two domains and one large study was at high risk of performance and detection bias.(a) Two studies with 13,934 participants at high cardiovascular risk provided efficacy data on intensive versus standard glycaemic control. A third study with 1791

  4. Effects of Changes in Potassium With Valsartan Use on Diabetes Risk: Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial

    Science.gov (United States)

    Thomas, Laine; Svetkey, Laura; Brancati, Frederick L.; Califf, Robert M.; Edelman, David

    2013-01-01

    BACKGROUND Low and low-normal serum potassium is associated with an increased risk of diabetes. We hypothesized that the protective effect of valsartan on diabetes risk could be mediated by its effect of raising serum potassium. METHODS We analyzed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial, which randomized participants at risk for diabetes to either valsartan (up to 160mg daily) or no valsartan. Using Cox models, we evaluated the effect of valsartan on diabetes risk over a median of 4 years of follow-up and calculated the mediation effect of serum potassium as the difference in treatment hazard ratios from models excluding and including 1-year change in serum potassium. The 95% confidence interval (CI) for the difference in log hazard ratios was computed by bootstrapping. RESULTS The hazard ratio for developing diabetes among those on valsartan vs. no valsartan was 0.866 (95% CI = 0.795–0.943) vs. 0.868 (95% CI = 0.797–0.945), after controlling for 1-year change in potassium. The bootstrap 95% CI for a difference in these log hazard ratios was not statistically significant (−0.003 to 0.009). CONCLUSIONS Serum potassium does not appear to significantly mediate the protective effect of valsartan on diabetes risk. PMID:23417031

  5. SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis.

    Science.gov (United States)

    Seidu, Samuel; Kunutsor, Setor K; Cos, Xavier; Gillani, Syed; Khunti, Kamlesh

    2018-06-01

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and 300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled. 42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m 2 ; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease. Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2

  6. Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation.

    Science.gov (United States)

    Herman, William H; Pan, Qing; Edelstein, Sharon L; Mather, Kieren J; Perreault, Leigh; Barrett-Connor, Elizabeth; Dabelea, Dana M; Horton, Edward; Kahn, Steven E; Knowler, William C; Lorenzo, Carlos; Pi-Sunyer, Xavier; Venditti, Elizabeth; Ye, Wen

    2017-12-01

    Both lifestyle and metformin interventions can delay or prevent progression to type 2 diabetes mellitus (DM) in people with impaired glucose regulation, but there is considerable interindividual variation in the likelihood of receiving benefit. Understanding an individual's 3-year risk of progressing to DM and regressing to normal glucose regulation (NGR) might facilitate benefit-based tailored treatment. We used the values of 19 clinical variables measured at the Diabetes Prevention Program (DPP) baseline evaluation and Cox proportional hazards models to assess the 3-year risk of progression to DM and regression to NGR separately for DPP lifestyle, metformin, and placebo participants who were adherent to the interventions. Lifestyle participants who lost ≥5% of their initial body weight at 6 months and metformin and placebo participants who reported taking ≥80% of their prescribed medication at the 6-month follow-up were defined as adherent. Eleven of 19 clinical variables measured at baseline predicted progression to DM, and 6 of 19 predicted regression to NGR. Compared with adherent placebo participants at lowest risk of developing diabetes, participants at lowest risk of developing diabetes who adhered to a lifestyle intervention had an 8% absolute risk reduction (ARR) of developing diabetes and a 35% greater absolute likelihood of reverting to NGR. Participants at lowest risk of developing diabetes who adhered to a metformin intervention had no reduction in their risk of developing diabetes and a 17% greater absolute likelihood of reverting to NGR. Participants at highest risk of developing DM who adhered to a lifestyle intervention had a 39% ARR of developing diabetes and a 24% greater absolute likelihood of reverting to NGR, whereas those who adhered to the metformin intervention had a 25% ARR of developing diabetes and an 11% greater absolute likelihood of reverting to NGR. Unlike our previous analyses that sought to explain population risk, these

  7. Long-term influences of body-weight changes, independent of the attained weight, on risk of impaired glucose tolerance and Type 2 diabetes

    DEFF Research Database (Denmark)

    Black, E; Holst, C; Astrup, A

    2005-01-01

    , but not by more recent weight gain in the later periods, probably because of the development of Type 2 diabetes leading to weight loss. CONCLUSIONS: Independent of attained level of body weight in middle-aged men, weight gain is associated with increased risk of IGT, and is greater in those not overweight......AIM: To investigate if weight gain during adulthood has effects on the risk of developing impaired glucose tolerance (IGT) or Type 2 diabetes beyond effect of attained weight. RESEARCH DESIGN AND METHODS: Data were obtained from a longitudinal study of two cohorts: one of juvenile-onset obese (n...... = 0.004), and weight gain during both the early and later ages contributed to the increased risk. Obese men, maintaining weight since age 20, had lower risk of IGT than non-obese men who became similarly obese by age 51. The risk of Type 2 diabetes increased by weight gain in early adult life...

  8. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study.

    Science.gov (United States)

    Li, Guangwei; Zhang, Ping; Wang, Jinping; An, Yali; Gong, Qiuhong; Gregg, Edward W; Yang, Wenying; Zhang, Bo; Shuai, Ying; Hong, Jing; Engelgau, Michael M; Li, Hui; Roglic, Gojka; Hu, Yinghua; Bennett, Peter H

    2014-06-01

    Lifestyle interventions among people with impaired glucose tolerance reduce the incidence of diabetes, but their effect on all-cause and cardiovascular disease mortality is unclear. We assessed the long-term effect of lifestyle intervention on long-term outcomes among adults with impaired glucose tolerance who participated in the Da Qing Diabetes Prevention Study. The study was a cluster randomised trial in which 33 clinics in Da Qing, China-serving 577 adults with impaired glucose tolerance-were randomised (1:1:1:1) to a control group or lifestyle intervention groups (diet or exercise or both). Patients were enrolled in 1986 and the intervention phase lasted for 6 years. In 2009, we followed up participants to assess the primary outcomes of cardiovascular mortality, all-cause mortality, and incidence of diabetes in the intention-to-treat population. Of the 577 patients, 439 were assigned to the intervention group and 138 were assigned to the control group (one refused baseline examination). 542 (94%) of 576 participants had complete data for mortality and 568 (99%) contributed data to the analysis. 174 participants died during the 23 years of follow-up (121 in the intervention group vs 53 in the control group). Cumulative incidence of cardiovascular disease mortality was 11.9% (95% CI 8.8-15.0) in the intervention group versus 19.6% (12.9-26.3) in the control group (hazard ratio [HR] 0.59, 95% CI 0.36-0.96; p=0.033). All-cause mortality was 28.1% (95% CI 23.9-32.4) versus 38.4% (30.3-46.5; HR 0.71, 95% CI 0.51-0.99; p=0.049). Incidence of diabetes was 72.6% (68.4-76.8) versus 89.9% (84.9-94.9; HR 0.55, 95% CI 0.40-0.76; p=0.001). A 6-year lifestyle intervention programme for Chinese people with impaired glucose tolerance can reduce incidence of cardiovascular and all-cause mortality and diabetes. These findings emphasise the long-term clinical benefits of lifestyle intervention for patients with impaired glucose tolerance and provide further justification for

  9. Metabolic syndrome, impaired fasting glucose and obesity, as predictors of incident diabetes in 14 120 hypertensive patients of ASCOT-BPLA: comparison of their relative predictability using a novel approach.

    Science.gov (United States)

    Gupta, A K; Prieto-Merino, D; Dahlöf, B; Sever, P S; Poulter, N R

    2011-08-01

    To evaluate, in hypertensive patients, whether the metabolic syndrome is a better predictor of new-onset diabetes compared with impaired fasting glucose, obesity or its other individual components alone, or collectively. Cox models were developed to assess the risk of new-onset diabetes associated with the metabolic syndrome after adjusting for a priori confounders (age, sex, ethnicity and concomitant use of non-cardiovascular medications), its individual components and other determinants of new-onset diabetes. Area under receiver operator curves using the metabolic syndrome or models of impaired fasting glucose were compared, and the ability of these models to correctly identify those who (after 5-years of follow-up) would or would not develop diabetes was assessed. The metabolic syndrome adjusted for a priori confounders and its individual components, and further adjusted for other determinants, was associated with significantly increased risk of new-onset diabetes [1.19 (1.00-1.40), P = 0.05 and 1.22 (1.03-1.44), P = 0.02, respectively]. The discriminative ability of the metabolic syndrome model [area under receiver operating curve: 0.764 (0.750-0.778)] was significantly better than the model of impaired fasting glucose [0.742 (0.727-0.757)] (P fasting glucose status (37.7%) (P fasting glucose were associated with an approximately 9-fold (7.47-10.45) increased risk of new-onset diabetes. Among normoglycaemic patients, the metabolic syndrome was also associated with significantly increased risk of new-onset diabetes, after adjusting for BMI and a priori confounders [1.66 (1.29-2.13)]. Both impaired fasting glucose and the metabolic syndrome predict the risk of new-onset diabetes; however, the metabolic syndrome is a better predictor than impaired fasting glucose in assigning the risk of new-onset diabetes in hypertensive patients, and among those with normoglycaemia. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  10. Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial.

    Science.gov (United States)

    Kothny, Wolfgang; Lukashevich, Valentina; Foley, James E; Rendell, Marc S; Schweizer, Anja

    2015-09-01

    There are limited data comparing dipeptidyl peptidase-4 (DPP-4) inhibitors directly. We compared the safety and efficacy of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment (RI). This study was a parallel-arm, randomised, multicentre, double-blind, 24 week study conducted in 87 centres across Brazil and the USA. Patients with type 2 diabetes, either drug naive or treated with any glucose-lowering agents, who had inadequate glycaemic control (HbA1c 6.5-10.0% [48-86 mmol/mol]) and an estimated GFR vildagliptin 50 mg once daily or sitagliptin 25 mg once daily. These doses are recommended in this patient population and considered maximally effective. Participants, investigators and the sponsor were blinded to group assignment. Efficacy endpoints included change in HbA1c and fasting plasma glucose (FPG) at all visits and the primary safety endpoint was assessment of treatment-emergent adverse events. In total, 148 patients were randomised, 83 to vildagliptin and 65 to sitagliptin. All patients were analysed. After 24 weeks, the adjusted mean change in HbA1c was -0.54% (5.9 mmol/mol) from a baseline of 7.52% (59 mmol/mol) with vildagliptin and -0.56% (6.1 mmol/mol) from a baseline of 7.80% (62 mmol/mol) with sitagliptin (p = 0.874). FPG decreased by 0.47 ± 0.37 mmol/l with vildagliptin and increased by 0.16 ± 0.43 mmol/l with sitagliptin (p = 0.185). Both treatments were well tolerated with overall similar safety profiles. At their recommended doses for severe RI, vildagliptin (50 mg once daily) compared with sitagliptin (25 mg once daily) demonstrated similar efficacy and both drugs were well tolerated. This study provides further support for the use of DPP-4 inhibitors in patients with severe RI. ClinicalTrials.gov NCT00616811 (completed) This study was planned and conducted by Novartis.

  11. Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires : The Cog-ID study

    NARCIS (Netherlands)

    Koekkoek, P. S.; Janssen, J.; Kooistra, M.; Biesbroek, J. M.; Groeneveld, O.; van den Berg, E.; Kappelle, L. J.; Biessels, G. J.; Rutten, G. E H M

    Aim: To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. Methods: Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous

  12. Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

    Science.gov (United States)

    Mager, U; Lindi, V; Lindström, J; Eriksson, J G; Valle, T T; Hämäläinen, H; Ilanne-Parikka, P; Keinänen-Kiukaanniemi, S; Tuomilehto, J; Laakso, M; Pulkkinen, L; Uusitupa, M

    2006-06-01

    Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

  13. Correlation between cognitive impairment and depressive mood of Thai elderly with type 2 diabetes in a primary care setting

    Directory of Open Access Journals (Sweden)

    Supaporn Trongsakul

    2015-07-01

    Full Text Available The prevalence of type 2 diabetes increases with age.1 More than 80% of people with diabetes live in low-and middle-income countries.2 Diabetes care is important in lowering blood glucose level and maintaining a good metabolic control in order to help prevent complication of diabetes. For successful diabetes self-management, individuals must commit to lifelong daily self-care tasks such as adhering to diet, exercise, medication regimens and checking blood glucose level. The coordination of these tasks often requires complex cognitive functioning.3

  14. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

    Science.gov (United States)

    Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

    2015-12-01

    Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

  15. Diabetes

    Science.gov (United States)

    ... you, discussing your symptoms, and going over your health history, your doctor may test for diabetes if he or she suspects you are at risk. To check for diabetes, your doctor may request the following tests: Fasting blood sugar test. This test is usually done ...

  16. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

    For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women...... with gestational diabetes mellitus is highly relevant....

  17. Study of the association between left ventricular diastolic impairment and cardiac autonomic neuropathy in diabetic patients using [123I] metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Suzuki, Rokuro; Tanaka, Shiro; Tojo, Osamu; Ishii, Tomofusa; Sato, Toshihiko; Fujii, Satoru; Tumura, Kei.

    1994-01-01

    The association between left ventricular (LV) diastolic dysfunction and myocardial MIBG accumulation was investigated. The subjects were 14 Type II diabetic patients who had no evidence of ischemic heat disease, LV hypertrophy or dilated cardiomyopathy as determined by exercise Tl-201 myocardial scintigraphy and echocardiography. In 14 diabetic patients, isovolumic relaxation time (IRT) was measured by M-mode echocardiography, and the subjects were subdivided into two groups: Group1, 8 patients with impaired left ventricular diastolic function (IRT≥80 msec), and Group 2, 6 patients with normal left ventricular diastolic function (IRT 123 I-MIBG myocardial scintigraphy was performed, and the myocardial accumulation of 123 I-MIBG was investigated. The ratio of myocardial to mediastinal MIBG uptake was significantly (p<0.01) lower in Group 1 than in Group 2. And scintigraphic defects were significantly (p<0.05) more numerous in Group 1 than in Group 2. Patients in Group 1 had a greater frequency of cardiac autonomic neuropathy evaluated by QTc interval and coefficient of variation of R-R interval, when compared with Group 2. These data suggest that, in diabetic patients with no evidence of ischemic heart disease, LV hypertrophy or dilated cardiomyopathy, impairment of left ventricular diastolic function is associated with cardiac autonomic neuropathy. (author)

  18. Prevalence of the impaired glucose metabolism and its association with risk factors for coronary artery disease in women with gestational diabetes.

    Science.gov (United States)

    Rivero, Katia; Portal, Vera Lúcia; Vieira, Matias; Behle, Ivo

    2008-03-01

    Gestational diabetes (GDM) has increased risk of diabetes (DM2), a coronary artery disease (CAD) equivalent. The aim of this study was to determine the prevalence of impaired glucose metabolism (IGM) in GDM and its association with risk factors for CAD. A cohort of 109 women with GDM underwent a glucose tolerance test which classified them into three groups: diabetic (DM2) (fasting glucose (G) >or=126mg/dl or plasma glucose 2h (2-h G) >or=200mg/dl); impaired glucose tolerance (IGT) (G 100-125mg/dl and/or 2-h G 140-199mg/dl); and normal (N) (GDM2, 39.4% IGT and 43.1% were N. PBMI, CBMI, SBP and DBP were significantly higher in the DM2 than N. G was higher in DM2 and IGT. HDL-cholesterol (HDL-C) was higher in the N (p=0.02) and the triglycerides (TG) were higher in DM2 (p=0.02). The groups showed significantly different levels of hsCRP (p=0.002). We conclude that the high prevalence of IGM, overweight/obesity, dyslipidemia and altered inflammatory markers, make GDM a high-risk situation for CAD.

  19. The Utility of the Mini-Addenbrooke's Cognitive Examination as a Screen for Cognitive Impairment in Elderly Patients with Chronic Kidney Disease and Diabetes.

    Science.gov (United States)

    Hobson, Peter; Rohoma, Kamel H; Wong, Stephen P; Kumwenda, Mick J

    2016-01-01

    We tested the utility of the Mini-Addenbrooke's Cognitive Examination (M-ACE) in a cohort of older adults with chronic kidney disease (CKD) and diabetes. The M-ACE was administered to 112 CKD and diabetes patients attending a nephrology clinic. Cognitive impairment was based upon patient, informant, and case review, neuropsychological assessment, and application of criteria for mild cognitive impairment (MCI) and the Diagnostic and Statistical Manual of Mental Disorders, fifth edition for dementia. The M-ACE was also compared to the Mini-Mental State Examination (MMSE). Upon assessment, 52 patients had normal cognitive function, 33 had MCI, and 27 had dementia. The area under the receiver operating curve for the M-ACE was 0.96 (95% CI 0.95-1.00). The sensitivity and specificity for a dementia diagnosis were 0.96 and 0.84 at the cut point <25 and 0.70 and 1.00 at the cut point <21. Mean M-ACE scores differed significantly between normal, demented, and MCI groups ( p < 0.001), and compared to the MMSE, the M-ACE did not suffer from ceiling effects. The M-ACE is an easily administered test with good sensitivity and specificity to capture and assist in the diagnosis of MCI or dementia in patients with CKD and diabetes.

  20. Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Penkowa, Milena; Hidalgo, Juan

    2005-01-01

    lower levels of MT-I+II were also detected in the plasma of type 2 diabetic subjects compared with control subjects. These results suggest that, in control subjects, the MT-I+II defense system is active and inducible within skeletal muscle tissue and plasma. In type 2 diabetes, reduced levels of MT......Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine....... Immunohistochemical analysis revealed reduced MT-I+II levels in the skeletal muscle of type 2 diabetic subjects compared with control subjects. Control subjects produced a robust increase of MT-I+II in response to training; however, in type 2 diabetes, MT-I+II levels remained essentially unchanged. Significantly...

  1. Pharmacokinetics and Pharmacodynamics of Luseogliflozin, a Selective SGLT2 Inhibitor, in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment.

    Science.gov (United States)

    Samukawa, Yoshishige; Haneda, Masakazu; Seino, Yutaka; Sasaki, Takashi; Fukatsu, Atsushi; Kubo, Yusuke; Sato, Yuri; Sakai, Soichi

    2018-04-25

    This open-label, parallel-group, multicenter study aimed to assess the effects of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of luseogliflozin. A single 5-mg dose of luseogliflozin was administered to Japanese patients with type 2 diabetes mellitus in the following groups: G1, normal renal function; G2, mild renal impairment; G3a, mild to moderate impairment; G3b, moderate to severe impairment; G4, severe impairment, based on estimated glomerular filtration rate (eGFR; ≥90, 60-89, 45-59, 30-44, 15-29 mL/min/1.73 m 2 , respectively). While luseogliflozin pharmacokinetics were similar for patients across all renal function groups, the increase in plasma concentration was slightly slower and maximum concentration was slightly reduced in the lower eGFR groups compared with the other groups. However, luseogliflozin pharmacodynamics were affected by the severity of renal impairment. Urinary glucose excretion (UGE) increased in all groups relative to baseline levels, but the degree of UGE increase was smaller in the lower eGFR groups. Moreover, plasma glucose AUC changes from baseline tended to be smaller in the lower eGFR groups. No clear trends were observed between eGFR and incidence, type, or severity of adverse events. Thus, luseogliflozin administration should be carefully considered, as patients with renal impairment may show an insufficient response to treatment. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  2. Addressing the common pathway underlying hypertension and diabetes in people who are obese by maximizing health: the ultimate knowledge translation gap.

    Science.gov (United States)

    Dean, Elizabeth; Lomi, Constantina; Bruno, Selma; Awad, Hamzeh; O'Donoghue, Grainne

    2011-03-06

    In accordance with the WHO definition of health, this article examines the alarming discord between the epidemiology of hypertension, type 2 diabetes mellitus (T2DM), and obesity and the low profile of noninvasive (nondrug) compared with invasive (drug) interventions with respect to their prevention, reversal and management. Herein lies the ultimate knowledge translation gap and challenge in 21st century health care. Although lifestyle modification has long appeared in guidelines for medically managing these conditions, this evidence-based strategy is seldom implemented as rigorously as drug prescription. Biomedicine focuses largely on reducing signs and symptoms; the effects of the problem rather than the problem. This article highlights the evidence-based rationale supporting prioritizing the underlying causes and contributing factors for hypertension and T2DM, and, in turn, obesity. We argue that a primary focus on maximizing health could eliminate all three conditions, at best, or, at worst, minimize their severity, complications, and medication needs. To enable such knowledge translation and maximizing health outcome, the health care community needs to practice as an integrated team, and address barriers to effecting maximal health in all patients. Addressing the ultimate knowledge translation gap, by aligning the health care paradigm to 21st century needs, would constitute a major advance.

  3. Addressing the Common Pathway Underlying Hypertension and Diabetes in People Who Are Obese by Maximizing Health: The Ultimate Knowledge Translation Gap

    Directory of Open Access Journals (Sweden)

    Elizabeth Dean

    2011-01-01

    Full Text Available In accordance with the WHO definition of health, this article examines the alarming discord between the epidemiology of hypertension, type 2 diabetes mellitus (T2DM, and obesity and the low profile of noninvasive (nondrug compared with invasive (drug interventions with respect to their prevention, reversal and management. Herein lies the ultimate knowledge translation gap and challenge in 21st century health care. Although lifestyle modification has long appeared in guidelines for medically managing these conditions, this evidence-based strategy is seldom implemented as rigorously as drug prescription. Biomedicine focuses largely on reducing signs and symptoms; the effects of the problem rather than the problem. This article highlights the evidence-based rationale supporting prioritizing the underlying causes and contributing factors for hypertension and T2DM, and, in turn, obesity. We argue that a primary focus on maximizing health could eliminate all three conditions, at best, or, at worst, minimize their severity, complications, and medication needs. To enable such knowledge translation and maximizing health outcome, the health care community needs to practice as an integrated team, and address barriers to effecting maximal health in all patients. Addressing the ultimate knowledge translation gap, by aligning the health care paradigm to 21st century needs, would constitute a major advance.

  4. Caffeine Consumption Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the Hippocampus of NONcZNO10/LTJ Mice

    OpenAIRE

    Duarte, João M. N.; Agostinho, Paula M.; Carvalho, Rui A.; Cunha, Rodrigo A.

    2012-01-01

    Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A(1) and A(2A) receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different...

  5. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

    Science.gov (United States)

    Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

    2017-01-01

    Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. PMID:28404095

  6. Predictive biomarkers for type 2 of diabetes mellitus: Bridging the gap between systems research and personalized medicine.

    Science.gov (United States)

    Kraniotou, Christina; Karadima, Vasiliki; Bellos, George; Tsangaris, George Th

    2018-03-05

    The global incidence of metabolic disorders like type 2 diabetes mellitus (DM2) has assumed epidemic proportions, leading to adverse health and socio-economic impacts. It is therefore of critical importance the early diagnosis of DM2 patients and the detection of those at increased risk of disease. In this respect, Precision Medicine (PM) is an emerging approach that includes practices, tests, decisions and treatments adapted to the characteristics of each patient. With regard to DM2, PM manages a wealth of "omics" data (genomic, metabolic, proteomic, environmental, clinical and paraclinical) to increase the number of clinically validated biomarkers in order to identify patients in early stage even before the prediabetic phase. In this paper, we discuss the epidemic dimension of metabolic disorders like type 2 diabetes mellitus (DM2) and the urgent demand for novel biomarkers to reduce the incidence or even delay the onset of DM2. Recent research data produced by "multi-omics" technologies (genomics/epigenomics, transcriptomics, proteomics and metabolomics), suggest that many potential biomarkers might be helpful in the prediction and early diagnosis of DM2. Predictive, Preventive and Personalized Medicine (PPPM) manages and integrates these data to apply personalized, preventive, and therapeutic approaches. This is significant because there is an emerging need for establishing channels for communication and personalized consultation between systems research and precision medicine, as the medicine of the future. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Mesenchymal stem cells ameliorate impaired wound healing through enhancing keratinocyte functions in diabetic foot ulcerations on the plantar skin of rats.

    Science.gov (United States)

    Kato, Jiro; Kamiya, Hideki; Himeno, Tatsuhito; Shibata, Taiga; Kondo, Masaki; Okawa, Tetsuji; Fujiya, Atsushi; Fukami, Ayako; Uenishi, Eita; Seino, Yusuke; Tsunekawa, Shin; Hamada, Yoji; Naruse, Keiko; Oiso, Yutaka; Nakamura, Jiro

    2014-01-01

    Although the initial healing stage involves a re-epithelialization in humans, diabetic foot ulceration (DFU) has been investigated using rodent models with wounds on the thigh skin, in which a wound contraction is initiated. In this study, we established a rodent model of DFU on the plantar skin and evaluated the therapeutic efficacy of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in this model. The wounds made on the hind paws or thighs of streptozotocin induced diabetic or control rats were treated with BM-MSCs. Expression levels of phosphorylated focal adhesion kinase (pFAK), matrix metaroprotease (MMP)-2, EGF, and IGF-1, were evaluated in human keratinocytes, which were cultured in conditioned media of BM-MSCs (MSC-CM) with high glucose levels. Re-epithelialization initiated the healing process on the plantar, but not on the thigh, skin. The therapy utilizing BM-MSCs ameliorated the delayed healing in diabetic rats. In the keratinocytes cultured with MSC-CM, the decreased pFAK levels in the high glucose condition were restored, and the MMP2, EGF, and IGF-1 levels increased. Our study established a novel rat DFU model. The impaired healing process in diabetic rats was ameliorated by transplantation of BM-MSCs. This amelioration might be accounted for by the modification of keratinocyte functions. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Diabetes

    Science.gov (United States)

    ... including: Blurry vision Excess thirst Fatigue Frequent urination Hunger Weight loss Because type 2 diabetes develops slowly, ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

  9. Diabetes

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for diabetes. The data is provided by three managed care organizations in Allegheny County (Gateway Health Plan,...

  10. The prevalence of depression in White-European and South-Asian people with impaired glucose regulation and screen-detected type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Aujla, Navneet; Abrams, Keith R.; Davies, Melanie J.

    2009-01-01

    ) and South-Asian (SA) population attending a community diabetes screening programme, and to explore the association of depression with screen-detected Type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR). Methodology/Principal Findings: Participants were recruited from general practices.......9% in WE, 26.4% in SA, p = 0.86). Age-adjusted prevalences were higher for females than males. Odds ratios adjusted for age, gender, and ethnicity, showed no significant increase in prevalent depression for people with T2DM (OR = 0.95, 95%CI 0.62 to 1.45) or IGR (OR = 1.17, 95%CI 0.96 to1.42). Conclusions......: Prior to the knowledge of diagnosis, depression was not significantly more prevalent in people with screen detected T2DM or IGR. Differences in prevalent depression between WE and SA people were also not identified. In this multi-ethnic population, female gender was significantly associated...

  11. Impaired autoregulation of cerebral blood flow in long-term type I (insulin-dependent) diabetic patients with nephropathy and retinopathy

    DEFF Research Database (Denmark)

    Kastrup, J; Rørsgaard, S; Parving, H H

    1986-01-01

    Autoregulation of cerebral blood flow, i.e., the maintenance of cerebral blood flow within narrow limits during changes in arterial perfusion pressure, was studied in nine healthy control subjects and in 12 long-term Type I (insulin-dependent) diabetic patients with clinical microangiopathy...... the previous findings suggesting that autoregulation of cerebral blood flow is impaired in some long-term Type I diabetic patients with clinical microangiopathy (arteriolar hyalinosis)........ Cerebral blood flow was measured by the intravenous 133Xenon method. Mean arterial blood pressure was elevated approximately 30 mmHg by intravenous infusion of angiotensin amide II and lowered about 10 mmHg by intravenous infusion of trimethaphan camsylate. In the control subjects the flow/pressure curve...

  12. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis.

    Science.gov (United States)

    Moran, Lisa J; Misso, Marie L; Wild, Robert A; Norman, Robert J

    2010-01-01

    BACKGROUND Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women associated with impaired glucose tolerance (IGT), type 2 diabetes mellitus (DM2) and the metabolic syndrome. METHODS A literature search was conducted (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) identifying studies reporting prevalence or incidence of IGT, DM2 or metabolic syndrome in women with and without PCOS. Data were presented as odds ratio (OR) [95% confidence interval (CI)] with fixed- and random-effects meta-analysis by Mantel-Haenszel methods. Quality testing was based on Newcastle-Ottawa Scaling and The Cochrane Collaboration's risk of bias assessment tool. Literature searching, data abstraction and quality appraisal were performed by two investigators. RESULTS A total of 2192 studies were reviewed and 35 were selected for final analysis. Women with PCOS had increased prevalence of IGT (OR 2.48, 95% CI 1.63, 3.77; BMI-matched studies OR 2.54, 95% CI 1.44, 4.47), DM2 (OR 4.43, 95% CI 4.06, 4.82; BMI-matched studies OR 4.00, 95% CI 1.97, 8.10) and metabolic syndrome (OR 2.88, 95% CI 2.40, 3.45; BMI-matched studies OR 2.20, 95% CI 1.36, 3.56). One study assessed IGT/DM2 incidence and reported no significant differences in DM2 incidence (OR 2.07, 95% CI 0.68, 6.30). One study assessed conversion from normal glucose tolerance to IGT/DM2 (OR 2.4, 95% CI 0.7, 8.0). No studies reported metabolic syndrome incidence. CONCLUSIONS Women with PCOS had an elevated prevalence of IGT, DM2 and metabolic syndrome in both BMI and non-BMI-matched studies. Few studies have determined IGT/DM2 or metabolic syndrome incidence in women with and without PCOS and further research is required.

  13. Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Qian Sun

    2018-03-01

    Full Text Available Aims: To investigate the white matter (WM integrity and hippocampal functional connectivity (FC in type 2 diabetes mellitus (T2DM patients without mild cognitive impairment (MCI by using diffusion tensor imaging (DTI and resting-state functional magnetic resonance imaging (rs-fMRI, respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS combining region of interests (ROIs analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA, mean diffusivity (MD, λ1 and λ23 and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE and Montreal Cognitive Assessment (MoCA. Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC. Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights-T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2

  14. Diabetes Mellitus Impairs Left Ventricular Mass Regression after Surgical or Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis.

    Science.gov (United States)

    Nakamura, Teruya; Toda, Koichi; Kuratani, Toru; Miyagawa, Shigeru; Yoshikawa, Yasushi; Fukushima, Satsuki; Saito, Shunsuke; Yoshioka, Daisuke; Kashiyama, Noriyuki; Daimon, Takashi; Sawa, Yoshiki

    2016-01-01

    It is well-documented that persistent myocardial hypertrophy in patients with aortic stenosis is related to suboptimal postoperative outcomes after aortic valve replacement. Although diabetes is known to potentially exacerbate myocardial hypertrophy, it has yet to be examined if it affects postoperative left ventricular mass regression (LVMR). A single-centre, retrospective analysis was performed on 183 consecutive patients who underwent either surgical or transcatheter aortic valve replacement between 2010 and May 2013. Patient demographics, postoperative outcomes and echocardiographic data were obtained preoperatively and a year after surgery. There were 42 diabetic and 141 non-diabetic patients. Preoperative characteristics of diabetic patients were statistically similar to those of non-diabetic patients, except for higher prevalence of hyperlipidaemia (p regression analysis demonstrated that diabetes (standardised partial regression coefficient (SPRC)=-0.187, p=0.018), female gender (SPRC=0.245, p=0.026) and age (SPRC=0.203, p=0.018) were associated with poor postoperative LVMR. Patients with diabetes showed suboptimal postoperative LVMR, and the disease was a prognostic factor that was associated with poor LVMR. These findings suggest that diabetes may predispose the particular group of patients to worse postoperative outcomes. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  15. Closing the knowledge gap on cardiovascular disease in type 2 diabetes: the EMPA-REG OUTCOME trial and beyond

    Directory of Open Access Journals (Sweden)

    Elif A Oral

    2016-09-01

    Full Text Available Type 2 diabetes mellitus (T2DM is associated with marked cardiovascular (CV morbidity and mortality, including heartfailure (HF. Until recently, an oral glucose-lowering agent that improved hyperglycemia as well as provided CV benefits in patients with T2DM and cardiovascular disease (CVD was lacking. The newest class of glucose-lowering agents, sodium glucose cotransporter 2 (SGLT2 inhibitors, includes canagliflozin, dapagliflozin, and empagliflozin. Prior to the release of the LEADER trial results, the recent EMPA-REG OUTCOME study was the only dedicated CV trial to demonstrate a reduction in major adverse cardiac events, CV mortality, and all-cause mortality and a reduction in hospitalization for HF with empagliflozin, given on top of standard-of-care therapy in patients with T2DM and CVD. This paper summarizes the results from EMPA-REG OUTCOME and discusses their significance and clinical implications.

  16. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

    DEFF Research Database (Denmark)

    Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio

    2014-01-01

    AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed...... the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

  17. Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus (T2DM) cases with impaired wound healing.

    Science.gov (United States)

    Singh, Kanhaiya; Agrawal, Neeraj K; Gupta, Sanjeev K; Sinha, Pratima; Singh, Kiran

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia which causes a chain of abrupt biochemical and physiological changes. Immune dys-regulation is the hallmark of T2DM that could contribute to prolonged inflammation causing transformation of wounds into non-healing chronic ulcers. Toll like receptor -9 (TLR9) is a major receptor involved in innate immune regulation. TLR9 activation induces release of pro-inflammatory molecules like S100A8 and interleukin-8 (IL-8) by myeloid cells causing migration of myeloid cells to the site of inflammation. We hypothesized that pro-inflammatory S100A8 and IL-8 proteins could cause persistent inflammation in chronic wounds like diabetic foot ulcer (DFU) and may contribute to impaired wound healing in T2DM patients. Expression of TLR9 and its downstream effector molecules S100A8, and IL-8 were analyzed in chronic diabetic wound and non-diabetic control wound tissue samples by semiquantitative reverse transcriptase - polymerase chain reaction (RT-PCR), quantitative RT-PCR, western blot and immunofluorescence. CD11b(+)CD33(+) myeloid cells were analyzed by flow cytometry. TLR9 message and protein were higher in diabetic wounds compared to control wounds (p=0.03, t=2.21 for TLR9 mRNA; p=diabetic wounds (p=0.003, t=3.1 for S100A8 mRNA; p=0.04, t=2.04 for IL-8). CD11b(+) CD33(+) myeloid cells were decreased in T2DM as compared to non-diabetic controls (p=0.001, t=3.6). DFU subjects had higher levels of CD11b(+) CD33(+) myeloid cells as compared to non-DFU T2DM control (p=0.003, t=2.8). Infection in the wound microenvironment could be the cause of increase in CD11b(+)CD33(+) myeloid cells in DFU (p=0.03, t=2.5). The up-regulation of myeloid cell-derived pro-inflammatory molecules S100A8 and IL-8 in combination with lower levels of CD11b(+) CD33(+) myeloid cells may cause the impairment of wound healing in T2DM subjects leading to chronic ulcers. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Glutamic acid decarboxylase autoantibody-positivity post-partum is associated with impaired β-cell function in women with gestational diabetes mellitus.

    Science.gov (United States)

    Lundberg, T P; Højlund, K; Snogdal, L S; Jensen, D M

    2015-02-01

    To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including β-cell function and insulin sensitivity. During 1997-2010, 407 women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin sensitivity and insulin secretion were estimated to assess insulin secretion adjusted for insulin sensitivity, disposition index (DI). Twenty-two (5.4%) women were positive for GAD autoantibodies (GAD+ve) and the remainder (94.6%) were negative for GAD autoantibodies (GAD-ve). The two groups had similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post-partum. Fasting levels of C-peptide and insulin were lower in GAD+ve women compared with GAD-ve women (520 vs. 761 pmol/l, P = 0.02 and 33 vs. 53 pmol/l, P = 0.05) Indices of insulin sensitivity were similar in GAD+ve and GAD-ve women, whereas all estimates of DI were significantly reduced in GAD+ve women. GAD+ve women had higher glucose levels and impaired insulin secretion adjusted for insulin sensitivity (DI) compared with GAD-ve women. The combination of OGTT and GAD autoantibodies post-partum identify women with impaired β-cell function. These women should be followed with special focus on development of Type 1 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  19. GAP Analysis Program (GAP)

    Data.gov (United States)

    Kansas Data Access and Support Center — The Kansas GAP Analysis Land Cover database depicts 43 land cover classes for the state of Kansas. The database was generated using a two-stage hybrid classification...

  20. Dynamics of heart rate variability analysed through nonlinear and linear dynamics is already impaired in young type 1 diabetic subjects.

    Science.gov (United States)

    Souza, Naiara M; Giacon, Thais R; Pacagnelli, Francis L; Barbosa, Marianne P C R; Valenti, Vitor E; Vanderlei, Luiz C M

    2016-10-01

    Autonomic diabetic neuropathy is one of the most common complications of type 1 diabetes mellitus, and studies using heart rate variability to investigate these individuals have shown inconclusive results regarding autonomic nervous system activation. Aims To investigate the dynamics of heart rate in young subjects with type 1 diabetes mellitus through nonlinear and linear methods of heart rate variability. We evaluated 20 subjects with type 1 diabetes mellitus and 23 healthy control subjects. We obtained the following nonlinear indices from the recurrence plot: recurrence rate (REC), determinism (DET), and Shanon entropy (ES), and we analysed indices in the frequency (LF and HF in ms2 and normalised units - nu - and LF/HF ratio) and time domains (SDNN and RMSSD), through analysis of 1000 R-R intervals, captured by a heart rate monitor. There were reduced values (p<0.05) for individuals with type 1 diabetes mellitus compared with healthy subjects in the following indices: DET, REC, ES, RMSSD, SDNN, LF (ms2), and HF (ms2). In relation to the recurrence plot, subjects with type 1 diabetes mellitus demonstrated lower recurrence and greater variation in their plot, inter-group and intra-group, respectively. Young subjects with type 1 diabetes mellitus have autonomic nervous system behaviour that tends to randomness compared with healthy young subjects. Moreover, this behaviour is related to reduced sympathetic and parasympathetic activity of the autonomic nervous system.

  1. Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes.

    Science.gov (United States)

    Laeger, Thomas; Castaño-Martinez, Teresa; Werno, Martin W; Japtok, Lukasz; Baumeier, Christian; Jonas, Wenke; Kleuser, Burkhard; Schürmann, Annette

    2018-06-01

    Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.

  2. Activin a is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes

    NARCIS (Netherlands)

    Chen, Weena J. Y.; Greulich, Sabrina; van der Meer, Rutger W.; Rijzewijk, Luuk J.; Lamb, Hildo J.; de Roos, Albert; Smit, Johannes W. A.; Romijn, Johannes A.; Ruige, Johannes B.; Lammertsma, Adriaan A.; Lubberink, Mark; Diamant, Michaela; Ouwens, D. Margriet

    2013-01-01

    Activin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic

  3. Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

    Science.gov (United States)

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2016-06-01

    The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; Pdiabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. © 2016 American Heart Association, Inc.

  4. Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Pardeep Kumar

    2015-01-01

    Full Text Available Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV and Trigonella foenum graecum seed powder (TSP administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase, intracellular calcium (Ca2+ levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

  5. Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats.

    Science.gov (United States)

    Kumar, Pardeep; Taha, Asia; Kumar, Nitin; Kumar, Vinod; Baquer, Najma Zaheer

    2015-01-01

    Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.

  6. Preserving Duodenal-Jejunal (Foregut) Transit Does Not Impair Glucose Tolerance and Diabetes Remission Following Gastric Bypass in Type 2 Diabetes Sprague-Dawley Rat Model.

    Science.gov (United States)

    Dolo, Ponnie R; Yao, Libin; Li, Chao; Zhu, Xiaocheng; Shi, Linsen; Widjaja, Jason

    2017-11-02

    Possible mechanisms underlying diabetes remission following Roux-en-Y gastric bypass (RYGB) include eradication of putative factor(s) with duodenal-jejunal bypass. The objective of this study is to observe the effects of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass rat model. In order to verify the effect of duodenal-jejunal transit on glucose tolerance and diabetes remission in gastric bypass, 22 type 2 diabetes Sprague-Dawley rat models established through high-fat diet and low-dose streptozotocin (STZ) administered intraperitoneally were assigned to one of three groups: gastric bypass with duodenal-jejunal transit (GB-DJT n = 8), gastric bypass without duodenal-jejunal transit (RYGB n = 8), and sham (n = 6). Body weight, food intake, blood glucose, as well as meal-stimulated insulin, and incretin hormone responses were assessed to ascertain the effect of surgery in all groups. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted three and 7 weeks after surgery. Comparing our GB-DJT to the RYGB group, we saw no differences in the mean decline in body weight, food intake, and blood glucose 8 weeks after surgery. GB-DJT group exhibited immediate and sustained glucose control throughout the study. Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels were also significantly increased from preoperative level in the GB-DJT group (p transit does not impede glucose tolerance and diabetes remission after gastric bypass in type-2 diabetes Sprague-Dawley rat model.

  7. Diabetic and nondiabetic patients with nonalcoholic fatty liver disease have an impaired incretin effect and fasting hyperglucagonaemia

    DEFF Research Database (Denmark)

    Junker, A E; Gluud, L; Holst, J J

    2016-01-01

    ; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect.......001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1) )] and without diabetes [7.5 pmol L......(-1) (5.0-8.0 pmol L(-1) )]. Fasting glucagon levels were lower but similar in patients with type 2 diabetes and no liver disease [4.5 pmol L(-1) (3.0-6.0 pmol L(-1) )] and controls [3.4 pmol L(-1) (1.8-6.0 pmol L(-1) )]. All groups had similar glucagon-like peptide-1 and glucose...

  8. Activation of the EPOR-β common receptor complex by cibinetide ameliorates impaired wound healing in mice with genetic diabetes.

    Science.gov (United States)

    Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Mannino, Federica; Vaccaro, Mario; Arcoraci, Vincenzo; Aliquò, Federica; Minutoli, Letteria; Colonna, Michele R; Galeano, Maria Rosaria; Brines, Michael; De Ponte, Chiara; Collino, Massimo; Squadrito, Francesco; Altavilla, Domenica

    2018-02-01

    Diabetes is characterized by poor wound healing which currently lacks an efficacious treatment. The innate repair receptor (IRR) is a master regulator of tissue protection and repair which is expressed as a response injury or metabolic stress, including in diabetes. Activation of the IRR might provide benefit for diabetic wound healing. A specific IRR agonist cibinetide was administered in an incisional wound healing model performed mice with genetic diabetes (db + /db + ) and compared to the normal wild-type. Animals were treated daily with cibinetide (30μg/kg/s.c.) or vehicle and euthanized 3, 7, and 14days after the injury to quantitate vascular endothelial growth factor (VEGF), malondialdehyde (MAL), phospho-Akt (pAkt), phospho e-NOS (p-eNOS), and nitrite/nitrate content within the wound. Additional evaluations included quantification of skin histological change, angiogenesis, scar strength, and time to complete wound closure. Throughout the wound healing process diabetic animals treated with vehicle exhibited increased wound MAL with reduced VEGF, pAkt, peNOS and nitrite/nitrate, all associated with poor re-epitheliziation, angiogenesis, and wound breaking strength. Cibenitide administration significantly improved these abnormalities. The results suggest that cibinetide-mediated IRR activation may represent an interesting strategy to treat diabetes-associated wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Impact of screening and early detection of impaired fasting glucose tolerance and type 2 diabetes in Canada: a Markov model simulation

    Directory of Open Access Journals (Sweden)

    Badawi A

    2012-04-01

    Full Text Available Soroush Mortaz*, Christine Wessman*, Ross Duncan, Rachel Gray, Alaa Badawi Office of Biotechnology Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, Canada*Both authors contributed equally to this workBackground: Type 2 diabetes mellitus (T2DM is a major global health problem. An estimated 20%–50% of diabetic subjects in Canada are currently undiagnosed, and around 20%–30% have already developed complications. Screening for high blood glucose levels can identify people with prediabetic conditions and permit introduction of timely and effective prevention. This study examines the benefit of screening for impaired fasting glucose (IFG and T2DM. If intervention is introduced at this prediabetic stage, it can be most effective in delaying the onset and complications of T2DM.Methods: Using a Markov model simulation, we compare the cost-effectiveness of screening for prediabetes (IFG and T2DM with the strategy of no screening. An initial cohort of normoglycemic, prediabetic, or undiagnosed diabetic adults with one or more T2DM risk factors was used to model the strategies mentioned over a 10-year period. Subjects without known prediabetes or diabetes are screened every 3 years and persons with prediabetes were tested for diabetes on an annual basis. The model weighs the increase in quality-adjusted life-years (QALYs associated with early detection of prediabetes and earlier diagnosis of T2DM due to lifestyle intervention and early treatment in asymptomatic subjects.Results: Costs for each QALY gained were $2281 for conventional screening compared with $2890 for no screening. Thus, in this base-case analysis, conventional screening with a frequency of once every 3 years was favored over no screening. Furthermore, conventional screening was more favorable compared with no screening over a wide range of willingness-to-pay thresholds. Changing the frequency of screening did not affect the overall results. Screening

  10. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Holman, Rury R; Coleman, Ruth L; Chan, Juliana C N; Chiasson, Jean-Louis; Feng, Huimei; Ge, Junbo; Gerstein, Hertzel C; Gray, Richard; Huo, Yong; Lang, Zhihui; McMurray, John J; Rydén, Lars; Schröder, Stefan; Sun, Yihong; Theodorakis, Michael J; Tendera, Michal; Tucker, Lynne; Tuomilehto, Jaakko; Wei, Yidong; Yang, Wenying; Wang, Duolao; Hu, Dayi; Pan, Changyu

    2017-11-01

    The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009

  11. Risk factors for visual impairment and blindness amongst black adult diabetics receiving treatment at Government healthcare facilities in Mopani District, Limpopo province, South Africa.

    Science.gov (United States)

    Mabaso, Raymond G; Oduntan, Olalekan A

    2014-11-21

    Diabetes mellitus (DM) is a common systemic disease amongst Black South Africans. It may lead to diabetic retinopathy (DR), a common cause of visual impairment (VI) and blindness. DR may signifiantly increase the prevalence of VI and blindness. To assess risk factors for VI and blindness amongst a black diabetic South African population aged ≥ 40 years. The study was conducted in seven Government healthcare facilities (two hospitals, four clinics and one health centre) in Mopani District, Limpopo province, South Africa. This was a cross-sectional health facility-based quantitative study. Structured interviews were used to obtain information, which included sociodemographic profie, knowledge about DM and its ocular complications, presence of hypertension and accessibility to health facilities. Subsequently participants were examined for VI and blindness using an autorefractor, pinhole disc, ophthalmoscope and logMAR visual acuity chart. Anthropometric measurements (height, weight and waist) were also taken. Associations between 31 risk factors and VI as well as blindness were statistically examined. Participants (N = 225) included 161 women and 64 men aged 40-90 years (mean 61.5 ± 10.49 years); 41.3% of them had VI and 3.6% were blind. Cataracts (76.8%) and DR (7.1%) were the common causes of compensated VI and blindness. Risk factors that were associated with VI and blindness were age, monthly income, compliance with losing weight and physical activity. Findings suggest that lifestyle intervention and appropriate eyecare programmes may reduce VI and blindness in this population.

  12. Association Between Sarcopenia and Mild Cognitive Impairment Using the Japanese Version of the SARC-F in Elderly Patients With Diabetes.

    Science.gov (United States)

    Ida, Satoshi; Nakai, Mari; Ito, Sho; Ishihara, Yuki; Imataka, Kanako; Uchida, Akihiro; Monguchi, Kou; Kaneko, Ryutaro; Fujiwara, Ryoko; Takahashi, Hiroka; Murata, Kazuya

    2017-09-01

    The purpose of this study was to investigate the association between sarcopenia and mild cognitive impairment (MCI) in elderly patients with diabetes using the Japanese version of the simple 5-item questionnaire (SARC-F-J). Cross-sectional study. Community hospital in Japan. Subjects were people with diabetes aged 65 years and older being treated on an outpatient basis at the Ise Red Cross Hospital. We used the Japanese version of the self-administered cognitive test Test Your Memory (TYM-J) to measure MCI and the self-administered questionnaire SARC-F-J, consisting of 5 items, to evaluate sarcopenia. We conducted a multiple logistic regression analysis with MCI as the dependent variable and sarcopenia as the explanatory variable to calculate the odds ratio of sarcopenia in association with MCI. A total of 250 cases (150 men and 100 women) were included in our study. The prevalence of sarcopenia in this sample was 19.5% and that of MCI was 40.3%. The adjusted odds ratio of sarcopenia in association with MCI was 2.96 (95% confidence interval, 1.09-7.70, P = .032). A statistically significant association was found between sarcopenia and MCI in an assessment of elderly patients with diabetes using the SARC-F-J. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  13. Relative contributions of energy expenditure on physical activity, body composition and weight gain to the evolution of impaired glucose to tolerance to Frank diabetes

    International Nuclear Information System (INIS)

    Forrester, T.; Wilks, R.; Gaskin, P.; Luke, A.; Jahoor, F.; Adeyemo, A.

    2002-01-01

    There is a gradient of diabetes prevalence among populations of the African Diaspora, with a rate of about 1% in West Africa, 12% in Jamaica and 16% in the United States. A population-based survey was conducted in an urban community in Jamaica to document the risk factors for the evolution of impaired glucose tolerance to frank diabetes. In a sample of 614 adults, 239 men and 375 women, oral glucose tolerance tests and examinations were conducted at Baseline and after 4-years of Follow-Up. There were significant increases in virtually all weight and adiposity variables for both men and women. Energy expenditure was also measured in a subset of participants at Follow-Up and was related significantly to glucose tolerance status. Among men, baseline age, weight, fat mass, body fat, waist circumference, and change in waist circumference were predictive of worsening glucose tolerance status. Among women, only age and change in waist circumference was a significant predictor. No physical activity parameter was predictive of change in tolerance status. These results provide support for the need to decrease adiposity as an important mechanism to control the rise in diabetes prevalence. (author)

  14. Multiple diabetic complications, as well as impaired physical and mental function, are associated with declining balance function in older persons with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Hong XF

    2017-01-01

    Full Text Available Xiufang Hong,1,2 Xujiao Chen,2 Jiaojiao Chu,2 Shanshan Shen,2 Qichen Chai,2 Gaobo Lou,2 Lingyan Chen2 1Zhejiang Chinese Medical University, 2Department of Geriatrics, Zhejiang Hospital, Hangzhou, Zhejiang, People’s Republic of China Objective: To investigate whether there is a difference in balance function between older persons with and without diabetes mellitus (DM, and to identify whether mediating factors, such as diabetic complications, Instrumental Activities of Daily Living (IADL score, Mini-Mental State Examination (MMSE score, as well as hemoglobin A1c (HbA1c, fasting plasma glucose (FPG, serum total cholesterol (TC, triglycerides (TG, and low-density lipoprotein (LDL, are associated with balance function in older persons with DM.Methods: In this cross-sectional study, a total of 208 older persons were divided into a DM group (n=80 and a control group who did not have DM (n=128. Balance function was evaluated with the Tinetti performance-oriented mobility assessment (POMA, which includes balance and gait subscales. Activities of daily living (ADL, IADL, and the MMSE were also measured. Fall incidents in last 12 months, the use of walking aids, fear of falling, comorbidities, and polypharmacy were recorded. Diabetic complications were recorded, and HbA1c, FPG, TC, TG, and LDL were measured in the patients of the DM group.Results: Fall incidents in last 12 months were higher in the DM group than in the control group (P<0.01. POMA score as well as ADL and IADL scores were lower in the diabetic group than the control group (P<0.05. Within the diabetic group, the POMA score was positively related to the ADL score (odds ratio [OR], 11.7; 95% confidence interval [CI], 3.076–44.497; P<0.01, IADL score (OR, 16.286; 95% CI, 4.793–55.333; P<0.01, and MMSE score (OR, 10.524; 95% CI, 2.764–40.074; P<0.01, but was negatively related to age (OR, 7.707; 95% CI, 2.035–29.185; P<0.01 and diabetic complication (OR, 6.667; 95% CI, 2.279–19

  15. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Directory of Open Access Journals (Sweden)

    Paramasivam Prabu

    Full Text Available Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM. While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT, impaired glucose tolerance (IGT and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  16. Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians—an ethnic population characterized to represent ‘Asian Indian phenotype’ known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a ‘New Lead’ in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes. PMID:26020947

  17. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    Science.gov (United States)

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

  18. Diabetes mellitus e intolerância à glicose são subdiagnosticados nas unidades de terapia intensiva Diabetes mellitus and impaired glucose tolerance are underdiagnosed in intensive care units

    Directory of Open Access Journals (Sweden)

    Renata Teixeira Ladeira

    2012-12-01

    Full Text Available OBJETIVO: Avaliar a presença de diabetes mellitus e a intolerância à glicose em pacientes internados em unidades de terapia intensiva. MÉTODOS: Foram incluídos pacientes clínicos, em pós-operatório de cirurgias eletivas e de urgência, e excluídos aqueles com história de diabetes mellitus. Para o diagnóstico de alterações prévias da glicemia, utilizou-se a dosagem da hemoglobina glicada (HbA1c na admissão do paciente, sendo classificado em normal (6,4%. Durante os 3 primeiros dias da internação, foram avaliados o controle glicêmico e as complicações clínicas. A evolução para óbito foi acompanhada por 28 dias. Para as análises estatísticas, utilizaram-se testes do qui-quadrado, ANOVA, teste t de Student, Kruskall-Wallis ou Mann Whitney. RESULTADOS: Foram incluídos 30 pacientes, 53% do gênero feminino, idade de 53,4±19,7 anos e APACHE II de 13,6±6,6. A maioria dos pacientes foi admitida por sepse grave ou choque séptico, seguido por pós-operatório de cirurgias eletivas, oncológicas, politraumatismo e cirurgia de urgência. Ao classificar esses pacientes segundo a HbA1c, apesar da ausência prévia de história de diabetes mellitus, apenas 13,3% tinham HbA1c normal, 23,3% tinham níveis compatíveis com o diagnóstico de diabetes mellitus e 63,3% eram compatíveis com intolerância à glicose. Houve associação significativa entre o diagnóstico de diabetes mellitus ou intolerância a glicose e o uso de droga vasoativa (p=0,04. CONCLUSÃO: Foi encontrada alta prevalência de diabetes mellitus e intolerância à glicose, sem diagnóstico prévio, em pacientes internados em uma unidade de terapia intensiva geral.OBJECTIVE: To evaluate the presence of diabetes mellitus and impaired glucose tolerance in intensive care unit inpatients. METHODS: The study included patients in post-surgical care for elective and emergency surgery and excluded those patients with known diabetes mellitus. To diagnose prior serum glucose

  19. Cholera toxin subunit B peptide fusion proteins reveal impaired oral tolerance induction in diabetes-prone but not in diabetes-resistant mice.

    Science.gov (United States)

    Presa, Maximiliano; Ortiz, Angela Zarama; Garabatos, Nahir; Izquierdo, Cristina; Rivas, Elisa I; Teyton, Luc; Mora, Conchi; Serreze, David; Stratmann, Thomas

    2013-11-01

    The cholera toxin B subunit (CTB) has been used as adjuvant to improve oral vaccine delivery in type 1 diabetes. The effect of CTB/peptide formulations on Ag-specific CD4(+) T cells has remained largely unexplored. Here, using tetramer analysis, we investigated how oral delivery of CTB fused to two CD4(+) T-cell epitopes, the BDC-2.5 T-cell 2.5 mi mimotope and glutamic acid decarboxylase (GAD) 286-300, affected diabetogenic CD4(+) T cells in nonobese diabetic (NOD) mice. When administered i.p., CTB-2.5 mi activated 2.5 mi(+) T cells and following intragastric delivery generated Ag-specific Foxp3(+) Treg and Th2 cells. While 2.5 mi(+) and GAD-specific T cells were tolerized in diabetes-resistant NODxB6.Foxp3(EGFP) F1 and nonobese resistant (NOR) mice, this did not occur in NOD mice. This indicated that NOD mice had a recessive genetic resistance to induce oral tolerance to both CTB-fused epitopes. In contrast to NODxB6.Foxp3(EGFP) F1 mice, oral treatment in NOD mice lead to strong 2.5 mi(+) T-cell activation and the sequestration of these cells to the effector-memory pool. Oral treatment of NOD mice with CTB-2.5 mi failed to prevent diabetes. These findings underline the importance of investigating the effect of oral vaccine formulations on diabetogenic T cells as in selected cases they may have counterproductive consequences in human patients. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

    Science.gov (United States)

    Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

    2013-09-05

    Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

  1. Impaired first-phase insulin response predicts postprandial blood glucose increment in patients with recently diagnosed type 2 diabetes

    DEFF Research Database (Denmark)

    Gredal, C; Rosenfalck, A M; Dejgaard, Anders

    2007-01-01

    The aim of the study was to evaluate the relationship between postprandial blood glucose and first-phase insulin response and, furthermore, to assess whether the intravenous glucagon stimulation test can be used as a predictor for increased postprandial glucose in patients with recently diagnosed...... type 2 diabetes....

  2. Impaired activity and gene expression of hexokinase II in muscle from non-insulin-dependent diabetes mellitus patients

    DEFF Research Database (Denmark)

    Vestergaard, H; Bjørbaek, C; Hansen, T

    1995-01-01

    -phosphate concentrations in muscle have been found in non-insulin-dependent diabetes mellitus (NIDDM) patients when examined during a hyperglycemic hyperinsulinemic clamp. These findings [correction of finding] are consistent with a defect in glucose transport and/or phosphorylation. In the present study...

  3. Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

    NARCIS (Netherlands)

    Meex, Steven J. R.; van Greevenbroek, Marleen M. J.; Ayoubi, Torik A.; Vlietinck, Robert; van Vliet-Ostaptchouk, Jana V.; Hofker, Martin H.; Vermeulen, Vicky M. M. -J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; de Bruin, Tjerk W. A.

    Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of

  4. Risk factors of impaired fasting glucose and type 2 diabetes in Yaounde, Cameroon : a cross sectional study

    NARCIS (Netherlands)

    Kufe, Clement Nyuyki; Klipstein-Grobusch, Kerstin; Leopold, Fezeu; Assah, Felix; Ngufor, George; Mbeh, George; Mbanya, Vivian Nchanchou; Mbanya, Jean Claude

    2015-01-01

    Background: The prevalence of diabetes is increasing worldwide, particularly in low and middle income countries, where treatment and control are often unavailable and inaccessible. Information on risk factors at local and regional levels is of utmost importance for tailored prevention programmes to

  5. The impact of severe hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Jørgensen, Hanne V; Pedersen-Bjergaard, Ulrik; Rasmussen, Ase K

    2003-01-01

    .01). CONCLUSIONS: Cohabitants of patients with type 1 diabetes recall significantly more episodes of severe hypoglycemia than the patients. The rate of severe hypoglycemia and state of hypoglycemic awareness are the principal determinants of degree of cohabitants' involvement in their partners' disease....

  6. Impaired exercise-related myocardial uptake of technetium-99m-tetrofosmin in relation to coronary narrowing and diabetic state

    International Nuclear Information System (INIS)

    Sasao, Hisataka; Nakata, Tomoaki; Tsuchihashi, Kazufumi; Wakabayashi, Takeru; Nakahara, Norifumi; Doi, Atsushi; Hashimoto, Akiyoshi; Kobayashi, Hiroshi; Shimamoto, Kazuaki

    2001-01-01

    Despite the diagnostic efficacy of stress myocardial perfusion imaging, the correlation between the actual perfusion tracer activity and diseased state of a coronary artery has not been studied in detail. We estimated exercise-related perfusion augmentation in relation to disease states of a coronary artery in diabetic and non-diabetic patients by a newly developed quantitative technetium (Tc)-99m-tetrofosmin myocardial imaging technique. Tc-99m-tetrofosmin tomographic imaging with an exercise-rest protocol was performed in 26 stable coronary patients and in 8 age-matched controls. Percent increase (%IR) in myocardial count during symptom-limited submaximal exercise-stress was calculated in 16 non-infarcted polar map segments and in each coronary territory by a subtraction technique with corrections for physical decay and injected tracer doses, and the results were compared with those of angiographically quantified coronary diameter stenosis (%DS). Percent IR and peak heart rate during exercise showed a positive linear correlation both in coronary territories with significant stenosis (%DS≥75%) and in control or non-stenotic (%DS<75%) territories. The regression line in stenotic regions was, however, significantly (p<0.01) shifted downward compared to that in non-stenotic regions. Percent IR in stenotic regions showed a significant inverse correlation with %DS. Coronary stenosis of 75% or more was identified by a %IR cutoff value of 40% with 77% sensitivity, 70% specificity, and an accuracy of 72%. In coronary territories with a %DS of less than 75%, %IR in diabetic patients was significantly lower (46±15%) than that in non-diabetic patients (61±25%). Thus, blunted exercise-related augmentation of myocardial uptake of Tc-99m-tetrofosmin correlates with the severity of coronary narrowing and diabetic state. (author)

  7. The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) update of the Finnish diabetes risk score for prediction of incident type 2 diabetes

    DEFF Research Database (Denmark)

    Alssema, M; Vistisen, D; Heymans, M W

    2011-01-01

    the ROC curve to 0.766 (95% CI 0.750-0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity. CONCLUSIONS/INTERPRETATION: The predictive value...... of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid...

  8. For Debate: Personalized Health Care: As Exemplified by Home Sodium Measurements in a Child with Central Diabetes Insipidus and Impaired Thirst Perception.

    Science.gov (United States)

    van der Linde, A A A; van Herwaarden, A E; Oosting, J D; Claahsen-van der Grinten, H L; de Grouw, E P L M

    2018-04-01

    We describe a 6-year old boy with central diabetes insipidus (CDI) caused by destruction of the pituitary gland due to treatment of an optical pathway glioma. He has been treated with chemotherapy and has had several debulking operations over the past years and consequently developed central hypocortisolism, hypothyroidism and CDI. The treatment of CDI was gravely complicated by an impaired thirst perception and compulsive drinking behavior. He was frequently seen at the ER or admitted due to dysregulation of fluid balance. In order to provide better self-reliance, home point of care testing (POCT) sodium measurement was introduced. Realizing POCT sodium measurement resulted in a significant decrease of ER visits and clinical admissions due to dysregulation of fluid balance. This case is an example of personalized health care and has led to better self-reliance and quality of life. Copyright© of YS Medical Media ltd.

  9. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease

    NARCIS (Netherlands)

    Cryns, K; Sivakumaran, TA; Van den Ouweland, JMW; Pennings, RJE; Cremers, CWRJ; Flothmann, K; Young, TL; Smith, RJH; Lesperance, MM; Van Camp, G

    2003-01-01

    WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition,

  10. Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.

    NARCIS (Netherlands)

    Cryns, K.; Sivakumaran, T.A.; Ouweland, J.M.W. van den; Pennings, R.J.E.; Cremers, C.W.R.J.; Flothmann, K.; Young, T.L.; Smith, R.J.H.; Lesperance, M.M.; Camp, G. van

    2003-01-01

    WFS1 is a novel gene and encodes an 890 amino-acid glycoprotein (wolframin), predominantly localized in the endoplasmic reticulum. Mutations in WFS1 underlie autosomal recessive Wolfram syndrome and autosomal dominant low frequency sensorineural hearing impairment (LFSNHI) DFNA6/14. In addition,

  11. Pre-teen insulin resistance predicts weight gain, impaired fasting glucose, and type 2 diabetes at age 18-19 y : a 10-y prospective study of black and white girls

    NARCIS (Netherlands)

    Morrison, John A.; Glueck, Charles J.; Horn, Paul S.; Schreiber, George B.; Wang, Ping

    2008-01-01

    Background: Identifying early pre-teen predictors of adolescent weight gain and the development of impaired fasting glucose (IFG) and type 2 diabetes (T2DM) at age 18-19 y could provide avenues for prevention. Objective: We evaluated possible pre-teen predictors for development of IFG, T2DM, and

  12. Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma

    Directory of Open Access Journals (Sweden)

    Lance A. Johnson

    2016-01-01

    Full Text Available Obesity, metabolic syndrome (MetS and type 2 diabetes (T2D are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D, multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV, a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.

  13. Increased Oxidation as an Additional Mechanism Underlying Reduced Clot Permeability and Impaired Fibrinolysis in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Anna Lados-Krupa

    2015-01-01

    Full Text Available Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks and clot lysis time induced by recombinant tissue plasminogen activator (CLT in 163 consecutive type 2 diabetic patients (92 men and 71 women aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c of 6.8%. We also measured oxidative stress markers, including nitrotyrosine, the soluble form of receptor for advanced glycation end products (sRAGE, 8-iso-prostaglandin F2α (8-iso-PGF2α, oxidized low-density lipoprotein (oxLDL, and advanced glycation end products (AGE. Results. There were inverse correlations between Ks and nitrotyrosine, sRAGE, 8-iso-PGF2α, and oxLDL. CLT showed a positive correlation with oxLDL and nitrotyrosine but not with other oxidation markers. All these associations remained significant for Ks after adjustment for fibrinogen, disease duration, and HbA1c (all P<0.05, while oxLDL was the only independent predictor of CLT. Conclusions. Our study shows that enhanced oxidative stress adversely affects plasma fibrin clot properties in type 2 diabetic patients, regardless of disease duration and glycemia control.

  14. Insulin Resistance Is Not Associated with an Impaired Mitochondrial Function in Contracting Gastrocnemius Muscle of Goto-Kakizaki Diabetic Rats In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Macia

    Full Text Available Insulin resistance, altered lipid metabolism and mitochondrial dysfunction in skeletal muscle would play a major role in type 2 diabetes mellitus (T2DM development, but the causal relationships between these events remain conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in Goto-Kakizaki (GK rats, a non-obese T2DM model developing peripheral insulin resistant without abnormal level of plasma non-esterified fatty acids (NEFA. Wistar rats were used as controls. Mechanical performance and energy metabolism were assessed strictly non-invasively using magnetic resonance (MR imaging and 31-phosphorus MR spectroscopy (31P-MRS. Compared with control group, plasma insulin and glucose were respectively lower and higher in GK rats, but plasma NEFA level was normal. In resting GK muscle, phosphocreatine content was reduced whereas glucose content and intracellular pH were both higher. However, there were not differences between both groups for basal oxidative ATP synthesis rate, citrate synthase activity, and intramyocellular contents for lipids, glycogen, ATP and ADP (an important in vivo mitochondrial regulator. During a standardized fatiguing protocol (6 min of maximal repeated isometric contractions electrically induced at a frequency of 1.7 Hz, mechanical performance and glycolytic ATP production rate were reduced in diabetic animals whereas oxidative ATP production rate, maximal mitochondrial capacity and ATP cost of contraction were not changed. These findings provide in vivo evidence that insulin resistance is not caused by an impairment of mitochondrial function in this diabetic model.

  15. Restoration of Impaired Metabolic Energy Balance (ATP Pool and Tube Formation Potential of Endothelial Cells under “high glucose”, Diabetic Conditions by the Bioinorganic Polymer Polyphosphate

    Directory of Open Access Journals (Sweden)

    Xiaohong Wang

    2017-11-01

    Full Text Available Micro-vascularization is a fast, energy-dependent process that is compromised by elevated glucose concentrations such as in diabetes mellitus disease. Here, we studied the effect of the physiological bioinorganic polymer, polyphosphate (polyP, on the reduced ATP content and impaired function of endothelial cells cultivated under “high glucose” (35 mM diabetes mellitus conditions concentrations. This high-energy biopolymer has been shown to provide a source of metabolic energy, stored in its phosphoanhydride bonds. We show that exposure of human umbilical vein endothelial cells (HUVEC cells to “high glucose” levels results in reduced cell viability, increased apoptotic cell death, and a decline in intracellular ATP level. As a consequence, the ability of HUVEC cells to form tube-like structures in the in vitro cell tube formation assay was almost completely abolished under “high glucose” conditions. Those cells were grown onto a physiological collagen scaffold (collagen/basement membrane extract. We demonstrate that these adverse effects of increased glucose levels can be reversed by administration of polyP to almost normal values. Using Na-polyP, complexed in a stoichiometric (molar ratio to Ca2+ ions and in the physiological concentration range between 30 and 300 µM, an almost complete restoration of the reduced ATP pool of cells exposed to “high glucose” was found, as well as a normalization of the number of apoptotic cells and energy-dependent tube formation. It is concluded that the adverse effects on endothelial cells caused by the metabolic energy imbalance at elevated glucose concentrations can be counterbalanced by polyP, potentially opening new strategies for treatment of the micro-vascular complications in diabetic patients.

  16. Progression from impaired glucose tolerance to type 2 diabetes in obese children and adolescents: a 3-6-year cohort study in southern Thailand.

    Science.gov (United States)

    Jaruratanasirikul, Somchit; Thammaratchuchai, Sudarat; Puwanant, Maneerat; Mo-Suwan, Ladda; Sriplung, Hutcha

    2016-11-01

    Childhood obesity is associated with abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). This study evaluated the prevalence of abnormal glucose metabolism in asymptomatic obese children and adolescents, and determined the percentage of T2DM development after 3-6 years of follow-up. During 2007-2013, 177 obese children and adolescents who had normal fasting plasma glucose (FPG100 mg/dL) were given an oral glucose tolerance test (OGTT). The participants were classified into four groups: normal glucose tolerance (NGT), NGT-hyperinsulinemia (NGT-HI), impaired glucose tolerance (IGT), and diabetes mellitus (DM). Blood chemistries, including FPG, glycated hemoglobin, and lipid profiles, and liver function test were performed every 6-12 months or when the patient developed any symptom or sign indicative of diabetes. Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p1). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. Glucose metabolism alteration was commonly found among obese adolescents. Factors associated with T2DM development were greater weight status and the severity of insulin resistance as shown by higher HOMA-IR levels.

  17. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin

    Science.gov (United States)

    Sambuceti, Gianmario; Morbelli, Silvia; Vanella, Luca; Kusmic, Claudia; Marini, Cecilia; Massollo, Michela; Augeri, Carla; Corselli, Mirko; Ghersi, Chiara; Chiavarina, Barbara; Rodella, Luigi F; L'Abbate, Antonio; Drummond, George; Abraham, Nader G; Frassoni, Francesco

    2009-01-01

    Background Atherosclerosis progression is accelerated in diabetes mellitus (DM) by either direct endothelial damage or reduced availability and function of endothelial progenitor cells (EPCs). Both alterations are related to increased oxidant damage. Aim We examined if DM specifically impairs vascular signaling, thereby reducing the recruitment of normal EPCs, and if increases in antioxidant levels by induction of heme oxygenase-1 (HO-1) can reverse this condition. Methods Control and diabetic rats were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) once a week for 3 weeks. Eight weeks after the development of diabetes, EPCs harvested from the aorta of syngenic inbred normal rats and labeled with technetium-99m-exametazime were infused via the femoral vein to estimate their blood clearance and aortic recruitment. Circulating endothelial cells (CECs) and the aortic expression of thrombomodulin (TM), CD31, and endothelial nitric oxide synthase (eNOS) were used to measure endothelial damage. Results DM reduced blood clearance and aortic recruitment of EPCs. Both parameters were returned to control levels by CoPP treatment without affecting EPC kinetics in normal animals. These abnormalities of EPCs in DM were paralleled by reduced serum adiponectin levels, increased numbers of CECs, reduced endothelial expression of phosphorylated eNOS, and reduced levels of TM, CD31, and phosphorylated AMP-activated protein kinase (pAMPK). CoPP treatment restored all of these parameters to normal levels. Conclusion Type II DM and its related oxidant damage hamper the interaction between the vascular wall and normal EPCs by mechanisms that are, at least partially, reversed by the induction of HO-1 gene expression, adiponectin, and pAMPK levels. PMID:19038792

  18. Prevalence of Type 2 Diabetes and Impaired Glucose Regulation with Associated Cardiometabolic Risk Factors and Depression in an Urbanizing Rural Community in Bangladesh: A Population-Based Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Bishwajit Bhowmik

    2012-12-01

    Full Text Available BackgroundTo determine the prevalence of type 2 diabetes (T2DM and impaired glucose regulation (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT] in an urbanizing rural population of Bangladesh and associated cardiometabolic risk indicators and depression.MethodsA total of 2,293 subjects aged ≥20 years in an urbanizing rural Bangladeshi community were investigated. Socio-demographic and anthropometric details, blood pressure, fasting plasma glucose (FPG, 2 hours after 75 g plasma glucose (2hPG, glycosylated hemoglobin, fasting serum insulin and lipid profiles were studied. Presence of depressive symptoms using Montogomery-Asberg Depression Rating Scale was also assessed.ResultsThe prevalence of IFG, IGT, IFG+IGT, and T2DM were 3.4%, 4.0%, 1.2%, and 7.9%, respectively. The prevalence of T2DM and impaired glucose regulation differed between males and females, but, both increased with age in both sexes. FPG and 2hPG had positive correlation. Employing logistic regression, it was found that increased age, waist to hip ratio, systolic blood pressure, total cholesterol, triglycerides, and depression were independent risk indicators for diabetes. Both insulin resistance and β-cell deficiency were significantly related for causation of diabetes. Among the study population, 26.2% had general obesity, 39.8% central obesity, 15.5% hypertension, 28.7% dyslipidemia, 17.6% family history of diabetes, and 15.3% had depression. Physical inactivity and smoking habits were significantly higher in male.ConclusionRising prevalence of diabetes and impaired glucose regulation in this urbanizing rural population exist as a significant but hidden public health problem. Depression and other cardiometabolic risk indicators including obesity, hypertension, and dyslipdemia were also prevalent in this population.

  19. Adipose-derived stem cells were impaired in restricting CD4+T cell proliferation and polarization in type 2 diabetic ApoE-/- mouse.

    Science.gov (United States)

    Liu, Ming-Hao; Li, Ya; Han, Lu; Zhang, Yao-Yuan; Wang, Di; Wang, Zhi-Hao; Zhou, Hui-Min; Song, Ming; Li, Yi-Hui; Tang, Meng-Xiong; Zhang, Wei; Zhong, Ming

    2017-07-01

    Atherosclerosis (AS) is the most common and serious complication of type 2 diabetes mellitus (T2DM) and is accelerated via chronic systemic inflammation rather than hyperglycemia. Adipose tissue is the major source of systemic inflammation in abnormal metabolic state. Pro-inflammatory CD4 + T cells play pivotal role in promoting adipose inflammation. Adipose-derived stem cells (ADSCs) for fat regeneration have potent ability of immunosuppression and restricting CD4 + T cells as well. Whether T2DM ADSCs are impaired in antagonizing CD4 + T cell proliferation and polarization remains unclear. We constructed type 2 diabetic ApoE -/- mouse models and tested infiltration and subgroups of CD4 + T cell in stromal-vascular fraction (SVF) in vivo. Normal/T2DM ADSCs and normal splenocytes with or without CD4 sorting were separated and co-cultured at different scales ex vivo. Immune phenotypes of pro- and anti-inflammation of ADSCs were also investigated. Flow cytometry (FCM) and ELISA were applied in the experiments above. CD4 + T cells performed a more pro-inflammatory phenotype in adipose tissue in T2DM ApoE -/- mice in vivo. Restriction to CD4 + T cell proliferation and polarization was manifested obviously weakened after co-cultured with T2DM ADSCs ex vivo. No obvious distinctions were found in morphology and growth type of both ADSCs. However, T2DM ADSCs acquired a pro-inflammatory immune phenotype, with secreting less PGE2 and expressing higher MHC-II and co-stimulatory molecules (CD40, CD80). Normal ADSCs could also obtain the phenotypic change after cultured with T2DM SVF supernatant. CD4 + T cell infiltration and pro-inflammatory polarization exist in adipose tissue in type 2 diabetic ApoE -/- mice. T2DM ADSCs had impaired function in restricting CD4 + T lymphocyte proliferation and pro-inflammatory polarization due to immune phenotypic changes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Impaired growth and force production in skeletal muscles of young partially pancreatectomized rats: a model of adolescent type 1 diabetic myopathy?

    Directory of Open Access Journals (Sweden)

    Carly S Gordon

    Full Text Available This present study investigated the temporal effects of type 1 diabetes mellitus (T1DM on adolescent skeletal muscle growth, morphology and contractile properties using a 90% partial pancreatecomy (Px model of the disease. Four week-old male Sprague-Dawley rats were randomly assigned to Px (n = 25 or Sham (n = 24 surgery groups and euthanized at 4 or 8 weeks following an in situ assessment of muscle force production. Compared to Shams, Px were hyperglycemic (>15 mM and displayed attenuated body mass gains by days 2 and 4, respectively (both P<0.05. Absolute maximal force production of the gastrocnemius plantaris soleus complex (GPS was 30% and 50% lower in Px vs. Shams at 4 and 8 weeks, respectively (P<0.01. GP mass was 35% lower in Px vs Shams at 4 weeks (1.24±0.06 g vs. 1.93±0.03 g, P<0.05 and 45% lower at 8 weeks (1.57±0.12 vs. 2.80±0.06, P<0.05. GP fiber area was 15-20% lower in Px vs. Shams at 4 weeks in all fiber types. At 8 weeks, GP type I and II fiber areas were ∼25% and 40% less, respectively, in Px vs. Shams (group by fiber type interactions, P<0.05. Phosphorylation states of 4E-BP1 and S6K1 following leucine gavage increased 2.0- and 3.5-fold, respectively, in Shams but not in Px. Px rats also had impaired rates of muscle protein synthesis in the basal state and in response to gavage. Taken together, these data indicate that exposure of growing skeletal muscle to uncontrolled T1DM significantly impairs muscle growth and function largely as a result of impaired protein synthesis in type II fibers.

  1. Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus and Impaired Renal Function: Interim Report from Post-marketing Surveillance.

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    Haneda, Masakazu; Kadowaki, Takashi; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Ishii, Manabu; Matsukawa, Miyuki; Ueno, Makoto

    2018-06-01

    Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from

  2. The Impact of Cognitive Impairment in Dementia on Self-Care Domains in Diabetes Mellitus: A Systematic Search and Narrative Review.

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    Santos, Tamsin; Lovell, Janaka; Shiell, Kerrie; Johnson, Marilyn; Ibrahim, Joseph E

    2018-04-29

    Self-management is integral to effective chronic disease management. Cognitive impairments (CogImp) associated with dementia have not previously been reviewed in diabetes mellitus (DM) self-care. (i) Whether CogImp associated with dementia impact self-care. (ii) Whether specific CogImp affects key DM self-care processes. A systematic literature search with a narrative review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This review examined studies published from January, 2000 to February, 2016 describing the relationship between cognition and DM self-care domains in community dwelling older adults with dementia/CogImp. Eight studies met inclusion criteria. Decrements in all self-care domains were associated with CogImp. Problem solving was related to reduced disease knowledge (OR 0.87, 95% CI=0.49-1.55), resulting in poorer glycemic control. Decision-making impairments manifested as difficulties in adjusting insulin doses, leading to more hospital admissions. People without CogImp were better able to find/utilize resources by adhering to recommended management (OR 1.03, 95% CI=1.02-1.05). A lack of interaction with health care providers was demonstrated through reduced receipt of important routine investigation including eye examinations (ARR=0.85, 95% CI=0.85-0.86), HbA1c testing (ARR=0.96, 95% CI=0.96-0.97) and LDL-C testing (ARR=0.91, 95% CI=0.901-0.914). People without CogImp had better clinic attendance (OR 2.17, 95% CI=1.30-3.70). Action taking deficits were apparent through less self-testing of blood sugar levels (20.2% vs 24.4%, p=0.1) resulting in poorer glycemic control, self-care and more frequent micro/macrovascular complications. Persons with diabetes and CogImp, particularly in domains of learning, memory and executive function, were significantly impaired in all self-care tasks. This article is protected by copyright. All rights reserved.

  3. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice.

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    Aleksunes, Lauren M; Reisman, Scott A; Yeager, Ronnie L; Goedken, Michael J; Klaassen, Curtis D

    2010-04-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic beta-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum beta-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels.

  4. Correlations of dietary energy and protein intakes with renal function impairment in chronic kidney disease patients with or without diabetes.

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    Chen, Mei-En; Hwang, Shang-Jyh; Chen, Hung-Chun; Hung, Chi-Chih; Hung, Hsin-Chia; Liu, Shao-Chun; Wu, Tsai-Jiin; Huang, Meng-Chuan

    2017-05-01

    Dietary energy and protein intake can affect progression of chronic kidney disease (CKD). CKD complicated with diabetes is often associated with a decline in renal function. We investigated the relative importance of dietary energy intake (DEI) and dietary protein intake (DPI) to renal function indicators in nondiabetic and diabetic CKD patients. A total of 539 Stage 3-5 CKD patients [estimated glomerular filtration rate (eGFR)Disease equation] with or without diabetes were recruited from outpatient clinics of Nephrology and Nutrition in a medical center in Taiwan. Appropriateness of DEI and DPI was used to subcategorize CKD patients into four groups:(1) kidney diet (KD) A (KD-A), the most appropriate diet, was characterized by low DPI and adequate DEI; (2) KD-B, low DPI and inadequate DEI; (3) KD-C, excess DPI and adequate DEI; and (4) KD-D, the least appropriate diet, excess DPI and inadequate DEI. Inadequate DEI was defined as a ratio of actual intake/recommended intake less than 90% and adequate DEI as over 90%. Low DPI was defined as less than 110% of recommended intake and excessive when over 110%. Outcome measured was eGFR. In both groups of CKD patients, DEI was significantly lower (ppatients were KD-C and KD-D significantly correlated with reduced eGFR compared with KD-A at increments of -5.63 mL/min/1.73 m 2 (p = 0.029) and -7.72 mL/min/1.73 m 2 (p=0.015). In conclusion, inadequate energy and excessive protein intakes appear to correlate with poorer renal function in nondiabetic CKD patients. Patients with advanced CKD are in need of counseling by dietitians to improve adherence to diets. Copyright © 2017. Published by Elsevier Taiwan.

  5. Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model of Type 2 Diabetes Mellitus

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    Andersen, Jens Velde; Nissen, Jakob Dahl; Christensen, Sofie Kjellerup

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer's disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine...... significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None...

  6. Defining the gap: a systematic review of the difference in rates of diabetes-related foot complications in Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians.

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    West, Matthew; Chuter, Vivienne; Munteanu, Shannon; Hawke, Fiona

    2017-01-01

    diabetes related foot complication compared to non-Indigenous Australians. Evidence-based, culturally appropriate screening and intervention programs and improved access to effective health care services are required to prevent a widening of the gap in diabetes related foot complications between Aboriginal and Torres Strait Islander and non-Indigenous Australians.

  7. Defining the gap: a systematic review of the difference in rates of diabetes-related foot complications in Aboriginal and Torres Strait Islander Australians and non-Indigenous Australians

    Directory of Open Access Journals (Sweden)

    Matthew West

    2017-11-01

    Australians have a 3–6 fold increased likelihood of experiencing a diabetes related foot complication compared to non-Indigenous Australians. Evidence-based, culturally appropriate screening and intervention programs and improved access to effective health care services are required to prevent a widening of the gap in diabetes related foot complications between Aboriginal and Torres Strait Islander and non-Indigenous Australians.

  8. Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β.

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    Gabbi, Chiara; Kong, Xiaomu; Suzuki, Hitoshi; Kim, Hyun-Jin; Gao, Min; Jia, Xiao; Ohnishi, Hideo; Ueta, Yoichi; Warner, Margaret; Guan, Youfei; Gustafsson, Jan-Åke

    2012-02-21

    The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.

  9. Type 2 diabetes and impaired glucose tolerance are associated with word memory source monitoring recollection deficits but not simple recognition familiarity deficits following water, low glycaemic load, and high glycaemic load breakfasts.

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    Lamport, Daniel J; Lawton, Clare L; Mansfield, Michael W; Moulin, Chris A J; Dye, Louise

    2014-01-30

    It has been established that type 2 diabetes, and to some extent, impaired glucose tolerance (IGT), are associated with general neuropsychological impairments in episodic memory. However, the effect of abnormalities in glucose metabolism on specific retrieval processes such as source monitoring has not been investigated. The primary aim was to investigate the impact of type 2 diabetes and IGT on simple word recognition (familiarity) and complex source monitoring (recollection). A secondary aim was to examine the effect of acute breakfast glycaemic load manipulations on episodic memory. Data are presented from two separate studies; (i) 24 adults with type 2 diabetes and 12 controls aged 45-75years, (ii) 18 females with IGT and 47 female controls aged 30-50years. Controls were matched for age, IQ, BMI, waist circumference, and depression. Recognition of previously learned words and memory for specifically which list a previously learned word had appeared in (source monitoring) was examined at two test sessions during the morning after consumption of low glycaemic load, high glycaemic load and water breakfasts according to a counterbalanced, crossover design. Type 2 diabetes (pglucose metabolism are not detrimental for global episodic memory processes. This enhances our understanding of how metabolic disorders are associated with memory impairments. © 2013.

  10. Correlations of dietary energy and protein intakes with renal function impairment in chronic kidney disease patients with or without diabetes

    Directory of Open Access Journals (Sweden)

    Mei-En Chen

    2017-05-01

    Full Text Available Dietary energy and protein intake can affect progression of chronic kidney disease (CKD. CKD complicated with diabetes is often associated with a decline in renal function. We investigated the relative importance of dietary energy intake (DEI and dietary protein intake (DPI to renal function indicators in nondiabetic and diabetic CKD patients. A total of 539 Stage 3–5 CKD patients [estimated glomerular filtration rate (eGFR<60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease equation] with or without diabetes were recruited from outpatient clinics of Nephrology and Nutrition in a medical center in Taiwan. Appropriateness of DEI and DPI was used to subcategorize CKD patients into four groups:(1 kidney diet (KD A (KD-A, the most appropriate diet, was characterized by low DPI and adequate DEI; (2 KD-B, low DPI and inadequate DEI; (3 KD-C, excess DPI and adequate DEI; and (4 KD-D, the least appropriate diet, excess DPI and inadequate DEI. Inadequate DEI was defined as a ratio of actual intake/recommended intake less than 90% and adequate DEI as over 90%. Low DPI was defined as less than 110% of recommended intake and excessive when over 110%. Outcome measured was eGFR. In both groups of CKD patients, DEI was significantly lower (p<0.001 and DPI higher (p=0.002 than recommended levels. However, only in the nondiabetic CKD patients were KD-C and KD-D significantly correlated with reduced eGFR compared with KD-A at increments of −5.63 mL/min/1.73 m2 (p = 0.029 and −7.72 mL/min/1.73 m2 (p=0.015. In conclusion, inadequate energy and excessive protein intakes appear to correlate with poorer renal function in nondiabetic CKD patients. Patients with advanced CKD are in need of counseling by dietitians to improve adherence to diets.

  11. Desarrollo de diabetes mellitus en pacientes con tolerancia a la glucosa alterada: Seguimiento de 18 años Development of diabetes mellitus in patients with impaired glucose tolerance: An 18-year follow-up

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    Pedro Perich Amador

    2002-08-01

    Full Text Available Se realizó un estudio prospectivo en 84 pacientes con diagnóstico de “tolerancia a la glucosa alterada” (TGA, desde hace 18 años, para conocer la prevalencia de diabetes mellitus (DM e identificar factores clínicos o metabólicos que pudieran estar asociados a la evolución desfavorable de esta afección. Se encontró que de los 114 sujetos con TGA que componían el grupo inicial, 25 (22 % habían fallecido. Se revisaron sus características iniciales y se halló que tenían un promedio de 10 años de edad más que los no fallecidos y frecuencia significativamente mayor de signos electrocardiográficos de cardiopatía isquémica, hipertensión arterial, hipercolesterolemia y hábito de fumar. En los 84 sujetos en los que se estudió la evolución metabólica, más de la mitad (53,6 % evolucionó a la DM, el 23,8 % se mantuvo con TGA y el 22,6 % restante, presentó tolerancia a la glucosa normal. No hubo relación entre las características clínicas en el estudio inicial y el tipo de evolución. Los sujetos que tenían al inicio “trastornos de la regulación de la glucemia en ayunas” (cifras ³ 6,1 mmol/L,18 años después presentaron mayor frecuencia de diabetes manifiesta que el resto, diferencia no significativa estadísticamente. Se concluyó que la TGA es un factor de riesgo importante para la DM2, y los trastornos de la regulación de la glucemia en ayunas, un estado avanzado de esta situación de riesgo por lo que se necesitan indicadores clínicos y metabólicos, asociados a la evolución desfavorable, que permitan establecer precozmente el nivel de riesgo de los sujetos con TGA.A prospective study was conducted among 84 patients that were diagnosed “impaired glucose tolerance” (IGT 18 years ago in order to know the prevalence of diabetes mellitus (DM and to identify clinical or metabolic factors that may be associated to an unfavorable evolution of this affection. It was found that of the 114 subjects with IGT that were

  12. Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes

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    Hansen, Jakob Schiøler; Pedersen, Bente Klarlund; Xu, Guowang

    2016-01-01

    blocking the increase in the glucagon to insulin ratio. In addition, we evaluated exercise-induced plasma FGF21 and follistatin in patients with T2D compared with healthy controls in response to 1 hour of bicycle exercise followed by a 3-hour recovery period. RESULTS: In healthy individuals, we observed......CONTEXT: Hepatokines have emerged as liver-derived hormone-like factors. Plasma fibroblast growth factor (FGF)-21 and follistatin increase with a high glucagon to insulin ratio and exercise, and resting levels are elevated in patients with type 2 diabetes (T2D). OBJECTIVE: The objective...... of the study was to investigate the regulatory roles of glucagon to insulin ratio and T2D on exercise-induced FGF21 and follistatin secretion. Design /Interventions: Young healthy males performed a 2-hour bicycle exercise bout followed by 5 hours of rest in supine position with and without a pancreatic clamp...

  13. Sustained Reduction in Severe Hypoglycemia in Adults With Type 1 Diabetes Complicated by Impaired Awareness of Hypoglycemia: 2-Year Follow-up in the HypoCOMPaSS Randomized Clinical Trial.

    Science.gov (United States)

    Little, Stuart A; Speight, Jane; Leelarathna, Lalantha; Walkinshaw, Emma; Tan, Horng Kai; Bowes, Anita; Lubina-Solomon, Alexandra; Chadwick, Thomas J; Stocken, Deborah D; Brennand, Catherine; Marshall, Sally M; Wood, Ruth; Kerr, David; Flanagan, Daniel; Heller, Simon R; Evans, Mark L; Shaw, James A M

    2018-04-16

    Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P diabetes complicated by impaired awareness of hypoglycemia. © 2018 by the American Diabetes Association.

  14. Study Protocol: The Norfolk Diabetes Prevention Study [NDPS]: a 46 month multi - centre, randomised, controlled parallel group trial of a lifestyle intervention [with or without additional support from lay lifestyle mentors with Type 2 diabetes] to prevent transition to Type 2 diabetes in high risk groups with non - diabetic hyperglycaemia, or impaired fasting glucose.

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    Pascale, Melanie; Murray, Nikki; Bachmann, Max; Barton, Garry; Clark, Allan; Howe, Amanda; Greaves, Colin; Sampson, Mike

    2017-01-06

    This 7 year NIHR programme [2011-2018] tests the primary hypothesis that the NDPS diet and physical activity intervention will reduce the risk of transition to type 2 diabetes (T2DM) in groups at high risk of Type 2 diabetes. The NDPS programme recognizes the need to reduce intervention costs through group delivery and the use of lay mentors with T2DM, the realities of normal primary care, and the complexity of the current glycaemic categorisation of T2DM risk. NDPS identifies people at highest risk of T2DM on the databases of 135 general practices in the East of England for further screening with ab fasting plasma glucose and glycosylated haemoglobin [HbA1c]. Those with an elevated fasting plasma glucose [impaired fasting glucose or IFG] with or without an elevated HbA1c [non -diabetic hyperglycaemia; NDH] are randomised into three treatment arms: a control arm receiving no trial intervention, an arm receiving an intensive bespoke group-based diet and physical activity intervention, and an arm receiving the same intervention with enhanced support from people with T2DM trained as diabetes prevention mentors [DPM]. The primary end point is cumulative transition rates to T2DM between the two intervention groups, and between each intervention group and the control group at 46 months. Participants with screen detected T2DM are randomized into an equivalent prospective controlled trial with the same intervention and control arms with glycaemic control [HbA1c] at 46 months as the primary end point. Participants with NDH and a normal fasting plasma glucose are randomised into an equivalent prospective controlled intervention trial with follow up for 40 months. The intervention comprises six education sessions for the first 12 weeks and then up to 15 maintenance sessions until intervention end, all delivered in groups, with additional support from a DPM in one treatment arm. The NDPS programme reports in 2018 and will provide trial outcome data for a group delivered

  15. Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    International Nuclear Information System (INIS)

    Devi, Sachin S.; Mehendale, Harihara M.

    2005-01-01

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G 0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G 1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

  16. Autonomic Neuropathy—a Prospective Cohort Study of Symptoms and E/I Ratio in Normal Glucose Tolerance, Impaired Glucose Tolerance, and Type 2 Diabetes

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    Malin Zimmerman

    2018-03-01

    Full Text Available BackgroundAutonomic neuropathy in diabetes, in addition to causing a range of symptoms originating from the autonomic nervous system, may increase cardiovascular morbidity. Our aim was to study the progression of autonomic neuropathy, based on symptom score and evaluation of an autonomic test, in persons with normal and impaired glucose tolerance and in patients with type 2 diabetes (T2D.MethodsParticipants were recruited in 2003/2004 with a follow-up in 2014. The participants’ glucose tolerance was categorized using oral glucose tolerance tests. Symptoms were evaluated using an autonomic symptom score (ASS, ECG was used to test cardiac autonomic function based on the expiration/inspiration ratio (E/I ratio, and blood samples were taken on both occasions.ResultsASSs were higher at follow-up in the T2D patients than in the normal glucose tolerance group (mean 1.21 ± 1.30 vs. 0.79 ± 0.7; p < 0.05. E/I ratio did not deteriorate more than could be expected as an aging effect in well-controlled T2D. No relationship was found between E/I ratio and HbA1c or ASS.ConclusionThe presence of autonomic symptoms increased over time in T2D patients, but the symptoms did not correlate with the E/I ratio in this metabolically well-controlled cohort. ASSs can be a useful clinical tool when assessing the progression of autonomic dysfunction in patients with abnormal glucose metabolism.

  17. ASSOCIATION OF CARDIORESPIRATORY FITNESS WITH ELEVATED HEPATIC ENZYME AND LIVER FAT IN JAPANESE PATIENTS WITH IMPAIRED GLUCOSE TOLERANCE AND TYPE 2 DIABETES MELLITUS

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    Mayumi Nagano

    2010-09-01

    Full Text Available No study has so far determined whether a favorable level of cardiorespiratory fitness (CF contributes to a reduced risk of elevated hepatic enzymes and a high degree of liver fat in patients having various metabolic risks. This study investigated the association between the maximal oxygen uptake (VO2 max and the prevalence of elevated liver enzymes and high liver fat, while considering such factors as abdominal obesity, hyperinsulinemia and the other metabolic risks. The study enrolled newly diagnosed Japanese patients (n = 84; 52 males and 32 females; aged 25-69 years with impaired glucose tolerance (IGT and type 2 diabetes mellitus (Type2DM who did not receive any intervention or pharmacological therapy. The subjects were divided into 3 groups according to the distribution of the VO2max for each sex. The odds ratios (ORs for the prevalence of elevated aspartate and alanine aminotransferase (AST and ALT and high degree of liver fat adjusted for age, sex, disease type, daily ethanol intake, and current smoking were significantly lower in the moderate- and high CF groups in comparison to the low CF group. In addition, a significant OR for AST was maintained in the moderate and high CF group after adjusting for abdominal obesity and/or hyperinsulinemia. The significant ORs for the prevalence of elevated ALT and a high degree of liver fat were attenuated after adjusting for abdominal obesity and/or hyperinsulinemia. No significant OR for the prevalence of elevated gamma-glutamyl transferase (GGT was recognized in all logistic models. These results indicated that CF was negatively and independently associated with the prevalence of elevated AST even in Japanese diabetic patients having various metabolic risks. It was concluded that the AST level might be useful as a simple marker reflecting physical inactivity in such subjects

  18. Vitamins Associated with Brain Aging, Mild Cognitive Impairment, and Alzheimer Disease: Biomarkers, Epidemiological and Experimental Evidence, Plausible Mechanisms, and Knowledge Gaps.

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    Fenech, Michael

    2017-11-01

    The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies. Current evidence suggests that all known vitamins and some "quasi-vitamins" are involved as cofactors or influence ≥1 of the 6 key sets of pathways or pathologies associated with MCI or AD, relating to 1 ) 1-carbon metabolism, 2 ) DNA damage and repair, 3 ) mitochondrial function and glucose metabolism, 4 ) lipid and phospholipid metabolism and myelination, 5 ) neurotransmitter synthesis and synaptogenesis, and 6 ) amyloidosis and Tau protein phosphorylation. The contemporary level of evidence for each of the vitamins varies considerably, but it is notable that B vitamins are involved as cofactors in all of the core pathways or pathologies and, together with vitamins C and E, are consistently associated with a protective role against dementia. Outcomes from recent studies indicate that the efficacy and safety of supplementation with vitamins to prevent MCI and the early stages of AD will most likely depend on 1 ) which pathways are defective, 2 ) which vitamins are deficient and could correct the relevant metabolic defects, and 3 ) the modulating impact of nutrient-nutrient and nutrient-genotype interaction. More focus on a precision nutrition approach is required to realize the full potential of vitamin therapy in preventing dementia and to avoid causing harm. © 2017 American Society for Nutrition.

  19. Association between the melatonin receptor 1B gene polymorphism on the risk of type 2 diabetes, impaired glucose regulation: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qing Xia

    Full Text Available BACKGROUND: Melatonin receptor 1B (MTNR1B belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction. METHODS: PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs and 95% confidence intervals (95% CIs were calculated. Heterogeneity and publication bias were also tested. RESULTS: A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153 on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02-1.08; P<10(-4 and 1.04 (95% CI: 0.98-1.10; P = 0.20 were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. CONCLUSIONS: This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D.

  20. Pregnancy induces molecular alterations reflecting impaired insulin control over glucose oxidative pathways that only in women with a family history of Type 2 diabetes last beyond pregnancy.

    Science.gov (United States)

    Piccinini, M; Mostert, M; Seardo, M A; Bussolino, S; Alberto, G; Lupino, E; Ramondetti, C; Buccinnà, B; Rinaudo, M T

    2009-01-01

    In circulating lymphomonocytes (CLM) of patients with Type 2 diabetes (DM2) pyruvate dehydrogenase (PDH), the major determinant of glucose oxidative breakdown, is affected by a cohort of alterations reflecting impaired insulin stimulated glucose utilization. The cohort is also expressed, although incompletely, in 40% of healthy young subjects with a DM2-family history (FH). Pregnancy restrains glucose utilization in maternal peripheral tissues to satisfy fetal requirements. Here we explore whether pregnant women develop the PDH alterations and, if so, whether there are differences between women with and without FH (FH+, FH-). Ten FH+ and 10 FH- were evaluated during pregnancy (12-14, 24-26, and 37-39 weeks) and 1 yr after (follow-up) for fasting plasma glucose and insulin as well as body mass index (BMI), and for the PDH alterations. Twenty FH- and 20 FH+ non-pregnant women served as controls. All FH+ and FH- controls exhibited normal clinical parameters and 8 FH+ had an incomplete cohort of PDH alterations. In FH- and FH+ pregnant women at 12-14 weeks clinical parameters were normal; from 24-26 weeks, with unvaried glucose, insulin and BMI rose more in FH- and only in the latter recovered the 12-14 weeks values at follow-up. In all FH-, the cohort of PDH alterations was incomplete at 24-26 weeks, complete at 37-39 weeks, and absent at follow-up but complete from 12-14 weeks including follow-up in all FH+. In FH-, the cohort is an acquired trait restricted to pregnancy signaling transiently reduced insulin-stimulated glucose utilization; in FH+, instead, it unveils the existence of an inherited DM2-related background these women all have, that is awakened by pregnancy and as such lastingly impairs insulin-stimulated glucose utilization.

  1. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

    DEFF Research Database (Denmark)

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María

    2017-01-01

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused...... of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes....

  2. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression.

    Science.gov (United States)

    Kakoly, N S; Khomami, M B; Joham, A E; Cooray, S D; Misso, M L; Norman, R J; Harrison, C L; Ranasinha, S; Teede, H J; Moran, L J

    2018-03-26

    Our prior meta-analyses demonstrated an increased prevalence of impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) with polycystic ovary syndrome (PCOS), but with substantial clinical heterogeneity. We aimed to update our previous review to quantify the prevalence of IGT and T2DM in PCOS with only quality studies (good and fair quality). We also aimed to examine the contribution of parameters including ethnicity, obesity and method of diagnosing T2DM in explaining the observed heterogeneity in IGT and T2DM prevalence in PCOS. We conducted a literature search (MEDLINE, CINAHL, EMBASE, clinical trial registries and hand-searching) up to June 2016 to identify studies reporting the prevalence of dysglycemia (IGT and T2DM) in women with and without PCOS. We included studies where women with PCOS (defined according to original National Institute of Health) were compared to women without PCOS for the end-points of the prevalence of IGT or T2DM. We excluded case reports, case series, editorials, and narrative reviews. Studies where PCOS was diagnosed by self-report, or where IGT or T2DM were measured by fasting glucose, only were excluded. We assessed the methodological quality of the included studies using a priori criteria based on the Newcastle-Ottawa Scaling (NOS) for non-randomized studies. Data are presented as odds ratio (OR) (95% CI) with random-effects meta-analysis by Mantel-Haenszel methods. We assessed the contribution of demographic and clinical factors to heterogeneity using subgroup and meta-regression analysis. We reviewed 4530 studies and included 40 eligible studies in the final analysis. On meta-analysis of quality studies, women with PCOS had an increased prevalence of IGT (OR = 3.26, 95% CI: 2.17-4.90) and T2DM (OR = 2.87, 95% CI: 1.44-5.72), which differed by ethnicity (for IGT, Asia: 5-fold, the Americas: 4-fold and Europe: 3-fold), was higher with obesity, and doubled among studies using self-report or administrative data for

  3. Plantar fascia enthesopathy is highly prevalent in diabetic patients without peripheral neuropathy and correlates with retinopathy and impaired kidney function.

    Science.gov (United States)

    Ursini, Francesco; Arturi, Franco; Nicolosi, Kassandra; Ammendolia, Antonio; D'Angelo, Salvatore; Russo, Emilio; Naty, Saverio; Bruno, Caterina; De Sarro, Giovambattista; Olivieri, Ignazio; Grembiale, Rosa Daniela

    2017-01-01

    Aim of this study was to evaluate the prevalence of plantar fascia (PF) enthesopathy in Type 2 diabetes mellitus (T2DM) patients without distal peripheral neuropathy (DPN). We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI). All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF. PF thickness was significantly higher in T2DM patients (p<0.0001). T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002), enthesophyte (p = 0.02) and cortical irregularity (p = 0.02). The overall sum of abnormalities was higher in T2DM patients (p<0.0001), as was the percentage of bilateral involvement (p = 0.005). In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05) and enthesophytes (OR 5.13, p = 0.001); reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04); body mass index (BMI) predicted cortical irregularity (OR 0.87, p = 0.05); mean glucose predicted enthesophyte (OR 1.01, p = 0.03); LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02). Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.

  4. Plantar fascia enthesopathy is highly prevalent in diabetic patients without peripheral neuropathy and correlates with retinopathy and impaired kidney function.

    Directory of Open Access Journals (Sweden)

    Francesco Ursini

    Full Text Available Aim of this study was to evaluate the prevalence of plantar fascia (PF enthesopathy in Type 2 diabetes mellitus (T2DM patients without distal peripheral neuropathy (DPN.We recruited 50 T2DM patients without DPN and 50 healthy controls. DPN was excluded using the Michigan Neuropathy Screening Instrument (MNSI. All patients underwent a bilateral sonographicevaluation of the enthesealportion of the PF.PF thickness was significantly higher in T2DM patients (p<0.0001. T2DM patients presented a higher prevalence of entheseal thickening (p = 0.002, enthesophyte (p = 0.02 and cortical irregularity (p = 0.02. The overall sum of abnormalities was higher in T2DM patients (p<0.0001, as was the percentage of bilateral involvement (p = 0.005. In a logistic regression analysis, retinopathy predicted entheseal thickening (OR 3.5, p = 0.05 and enthesophytes (OR 5.13, p = 0.001; reduced eGFR predicted enthesophytes (OR 2.93, p = 0.04; body mass index (BMI predicted cortical irregularity (OR 0.87, p = 0.05; mean glucose predicted enthesophyte (OR 1.01, p = 0.03; LDL cholesterol predicted cortical irregularity (OR 0.98, p = 0.02.Our data suggest that T2DM is associated with PF enthesopathyindependently of DPN.

  5. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity

    DEFF Research Database (Denmark)

    Knop, Filip K; Aaboe, K; Vilsbøll, T

    2012-01-01

    Aims: People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated a and ß-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM...... or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Methods: Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m(2) ]; (ii) Eight obese...... subjects with NGT [BMI: 33 (35-38) kg/m(2) ]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m(2) ]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m(2) ]. Results: The incretin effect was significantly (p T2DM {obese: 7 ± 7% [mean ± standard error...

  6. Hearing impairment in genotyped Wolfram syndrome patients.

    NARCIS (Netherlands)

    Plantinga, R.F.; Pennings, R.J.E.; Huygen, P.L.M.; Bruno, R.; Eller, P.; Barrett, T.G.; Vialettes, B.; Paquis-Fluklinger, V.; Lombardo, F.; Cremers, C.W.R.J.

    2008-01-01

    OBJECTIVES: Wolfram syndrome is a progressive neurodegenerative syndrome characterized by the features "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). We sought to study the audiometric data of genotyped Wolfram syndrome patients with sensorineural hearing impairment.

  7. Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

    Directory of Open Access Journals (Sweden)

    Zainab Jahangir

    2014-01-01

    Full Text Available Impaired insulin signaling has been thought of as important step in both Alzheimer’s disease (AD and type 2 diabetes mellitus (T2DM. Posttranslational modifications (PTMs regulate functions and interaction of insulin with insulin receptors substrates (IRSs and activate insulin signaling downstream pathways via autophosphorylation on several tyrosine (TYR residues on IRSs. Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser and threonine (Thr residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation modification is important PTM and inhibits phosphorylation on same or neighboring Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been shown to be O-glycosylated; however exact sites are not determined yet. In this study, by using neuronal network based prediction methods, we found more than 50 Ser/Thr residues that have potential to be O-glycosylated and may act as possible sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1 Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize the risk of AD and T2DM.

  8. Cerebral hemodynamics and systemic endothelial function are already impaired in well-controlled type 2 diabetic patients, with short-term disease.

    Directory of Open Access Journals (Sweden)

    Paola Palazzo

    Full Text Available Impaired cerebral vasomotor reactivity (VMR and flow-mediated dilation (FMD were found in selected subgroups of type 2 diabetes mellitus (T2DM patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN.Twenty-six T2DM patients with short-term (4.40±4.80 years and well-controlled (HbA1C = 6.71±1.29% disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also.FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p.05.In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.

  9. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity.

    Science.gov (United States)

    Knop, Filip K; Aaboe, K; Vilsbøll, T; Vølund, A; Holst, J J; Krarup, T; Madsbad, S

    2012-06-01

    People with type 2 diabetes mellitus (T2DM) are characterized by reduced incretin effect and inappropriate glucagon levels. We evaluated α and β-cell responses to oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI) in lean and obese persons with T2DM or normal glucose tolerance (NGT) to elucidate the impact of obesity on the incretin effect and incretin hormone and glucagon responses. Four hour 50-g OGTT and IIGI were performed in (i) Eight obese patients with T2DM [mean body mass index (BMI): 37 (range: 35-41) kg/m(2)]; (ii) Eight obese subjects with NGT [BMI: 33 (35-38) kg/m(2)]; (iii) Eight lean patients with T2DM [BMI: 24 (22-25) kg/m(2)]; and (iv) Eight lean healthy subjects [BMI: 23 (20-25) kg/m(2)]. The incretin effect was significantly (p obese: 7 ± 7% [mean ± standard error of the mean (SEM)]; lean: 29 ± 8%; p = 0.06)} and was lower in obese subjects (41 ± 4%) than in lean subjects with NGT (53 ± 4%; p Obese subjects with NGT were also characterized by elevated fasting plasma glucagon levels, but the inappropriate glucagon responses to OGTT found in the T2DM patients were not evident in these subjects. Our findings suggest that reduced incretin effect and fasting hyperglucagonaemia constitute very early steps in the pathophysiology of T2DM detectable even in obese people who despite their insulin-resistant state have NGT. © 2011 Blackwell Publishing Ltd.

  10. Association between poor glycemic control, impaired sleep quality, and increased arterial thickening in type 2 diabetic patients.

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    Koichiro Yoda

    Full Text Available Poor sleep quality is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and objective sleep architecture and its influence on arteriosclerosis in patients with type-2 diabetes mellitus (DM. The present study examined the association of objective sleep architecture with both glycemic control and arteriosclerosis in type-2 DM patients.Cross-sectional study in vascular laboratory.The subjects were 63 type-2 DM inpatients (M/F, 32/31; age, 57.5±13.1 without taking any sleeping promoting drug and chronic kidney disease. We examined objective sleep architecture by single-channel electroencephalography and arteriosclerosis by carotid-artery intima-media thickness (CA-IMT.HbA1c was associated significantly in a negative manner with REM sleep latency (interval between sleep-onset and the first REM period (β=-0.280, p=0.033, but not with other measurements of sleep quality. REM sleep latency associated significantly in a positive manner with log delta power (the marker of deep sleep during that period (β=0.544, p=0.001. In the model including variables univariately correlated with CA-IMT (REM sleep latency, age, DM duration, systolic blood pressure, and HbA1c as independent variables, REM sleep latency (β=-0.232, p=0.038, but not HbA1c were significantly associated with CA-IMT. When log delta power was included in place of REM sleep latency, log delta power (β=-0.257, p=0.023 emerged as a significant factor associated with CA-IMT.In type-2 DM patients, poor glycemic control was independently associated with poor quality of sleep as represented by decrease of REM sleep latency which might be responsible for increased CA-IMT, a relevant marker for arterial wall thickening.

  11. Ranibizumab for Visual Impairment due to Diabetic Macular Edema: Real-World Evidence in the Italian Population (PRIDE Study

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    Ugo Menchini

    2015-01-01

    Full Text Available Purpose. An expanded access program (PRIDE study in Italy to provide ranibizumab 0.5 mg to diabetic macular edema (DME patients, prior to reimbursement. Methods. Open-label, prospective, phase IIIb study. Majority of patients were not treatment-naïve before enrollment. Patients received ranibizumab as per the EU label (2011. Safety was assessed by incidences of ocular/systemic adverse events (AEs and serious AEs (SAEs and efficacy in terms of visual acuity (VA change from baseline (decimal score or Snellen (20/value. Results. Overall, 515 patients (83.5% completed the study. In unilateral/bilateral patients, commonly observed AEs were cardiac disorders (1.3%/1.3% and nervous system disorders (1.3%/1.1%; SAEs were reported in 4.5%/4.8% of patients. Acute renal failure, lung carcinoma, and cardiac arrest were the causes of death in one unilateral and two bilateral patients. Ranibizumab improved/maintained VA (Snellen (20/value/decimal scores in both unilateral (up to −16.7/1.5 and bilateral patients (up to −23.6/1.2 at Month 5, with a mean of 4.15 and 4.40 injections, respectively. Overall, no difference was observed in the VA outcomes and treatment exposure between unilateral/bilateral patients. Conclusions. The PRIDE study provided early ranibizumab access to >600 Italian patients. Ranibizumab was well-tolerated and improved/maintained VA in 40.2%–68.8% patients, with no differences in case of unilateral or bilateral pathology. The study is registered with EudraCT.

  12. Factores metabólicos asociados con la progresión hacia la diabetes mellitus en sujetos con tolerancia a la glucosa alterada Metabolic factors associated with the progression of diabetes mellitus in subjects with impaired glucose tolerance

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    Roberto M. González Suárez

    2007-12-01

    Full Text Available Se realizó un estudio prospectivo en 84 pacientes con tolerancia a la glucosa alterada (TGA, diagnosticada 18 años antes, para identificar factores metabólicos identificados en el estudio inicial, que pudieran estar asociados a la progresión hacia la diabetes mellitus (DM detectada en el estudio evolutivo. Como factores de riesgo metabólicos se consideraron la gravedad del trastorno de la tolerancia a la glucosa, la disminución o incremento de la secreción de insulina en ayunas y durante una PTG oral, así como la resistencia a la insulina detectada en ayunas o durante la PTG, todos ellos determinados con métodos y criterios de interpretación previamente establecidos y validados. Se encontró que la presencia de una baja respuesta insulínica inicial (II0-30 disminuido se asocia significativamente con la progresión hacia la diabetes en el grupo de sujetos con TGA estudiados. Este hallazgo es consistente en todos los aspectos del fenómeno evaluado (valores absolutos de las variables en los grupos de sujetos clasificados de acuerdo con su evolución, riesgo de evolución hacia la DM y tiempo hasta el diagnóstico de DM y está de acuerdo con el criterio de que el factor genéticamente determinado que condiciona el desarrollo de la DM es un defecto de la capacidad inicial de respuesta insulinosecretora a los cambios de la glicemia.A prospective study was conducted in 84 patients with impaired glucose tolerance (IGT diagnosed 18 years before to identify metabolic factors found in the initial study that could be associated with the progression to diabetes mellitus (DM detected in the evolutive study. The severity of the glucose tolerance disorder, the reduction or increase of insulin secretion on fasting or during an oral glucose tolerance test (OGTT, as well as the resistance to insulin detected on fasting or during the OGTT, were considered as risk factors. All of them were determined by methods and criteria of interpretation that were

  13. Can we bridge the gap? Knowledge and practices related to Diabetes Mellitus among general practitioners in a developing country: A cross sectional study.

    Science.gov (United States)

    Katulanda, Prasad; Constantine, Godwin R; Weerakkody, Muditha I; Perera, Yashasvi S; Jayawardena, Mahesh G; Wijegoonawardena, Preethi; Matthews, David R; Sheriff, Mohamed Hr

    2011-11-24

    Diabetes mellitus is becoming a serious public health problem in Sri Lanka and many other developing countries in the region. It is well known that effective management of diabetes reduces the incidence and progression of many diabetes related complications, thus it is important that General Practitioners (GPs) have sound knowledge and positive attitudes towards all aspects of its management. This study aims to assess knowledge, awareness and practices relating to management of Diabetes Mellitus among Sri Lankan GPs. A cross-sectional study was conducted among all 246 GPs registered with the Ceylon College of General Practitioners using a pre-validated self-administered questionnaire. 205 responded to the questionnaire(response rate 83.3%). Their mean duration of practice was 28.7 ± 11.2 years. On average, each GP had 27 ± 25 diabetic-patient consultations per-week. 96% managed diabetic patients and 24% invariably sought specialist opinion. 99.2% used blood glucose to diagnose diabetes but correct diagnostic cut-off values were known by only 48.8%. Appropriate use of HbA1c and urine microalbumin was known by 15.2% and 39.2% respectively. 84% used HbA1c to monitor glyceamic control, while 90.4% relied on fasting blood glucose to monitor glyceamic control. Knowledge on target control levels was poor.Nearly 90% correctly selected the oral hypoglyceamic treatment for obese as well as thin type 2 diabetic patients. Knowledge on the management of diabetes in pregnancy was poor. Only 23.2% knew the correct threshold for starting lipid-lowering therapy. The concept of strict glycaemic control in preference to symptom control was appreciated only by 68%. The skills for comprehensive care in subjects with multiple risk factors were unsatisfactory. The study was done among experienced members of the only professional college dedicated to the specialty. However, we found that there is room for improvement in their knowledge and practices related to diabetes. We recommend

  14. Can we bridge the gap? Knowledge and practices related to Diabetes Mellitus among general practitioners in a developing country: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Katulanda Prasad

    2011-11-01

    Full Text Available Abstract Background Diabetes mellitus is becoming a serious public health problem in Sri Lanka and many other developing countries in the region. It is well known that effective management of diabetes reduces the incidence and progression of many diabetes related complications, thus it is important that General Practitioners (GPs have sound knowledge and positive attitudes towards all aspects of its management. This study aims to assess knowledge, awareness and practices relating to management of Diabetes Mellitus among Sri Lankan GPs. Methods A cross-sectional study was conducted among all 246 GPs registered with the Ceylon College of General Practitioners using a pre-validated self-administered questionnaire. Results 205 responded to the questionnaire(response rate 83.3%. Their mean duration of practice was 28.7 ± 11.2 years. On average, each GP had 27 ± 25 diabetic-patient consultations per-week. 96% managed diabetic patients and 24% invariably sought specialist opinion. 99.2% used blood glucose to diagnose diabetes but correct diagnostic cut-off values were known by only 48.8%. Appropriate use of HbA1c and urine microalbumin was known by 15.2% and 39.2% respectively. 84% used HbA1c to monitor glyceamic control, while 90.4% relied on fasting blood glucose to monitor glyceamic control. Knowledge on target control levels was poor. Nearly 90% correctly selected the oral hypoglyceamic treatment for obese as well as thin type 2 diabetic patients. Knowledge on the management of diabetes in pregnancy was poor. Only 23.2% knew the correct threshold for starting lipid-lowering therapy. The concept of strict glycaemic control in preference to symptom control was appreciated only by 68%. The skills for comprehensive care in subjects with multiple risk factors were unsatisfactory. Conclusions The study was done among experienced members of the only professional college dedicated to the specialty. However, we found that there is room for improvement in

  15. Diabetes among Inuit migrants in Denmark

    DEFF Research Database (Denmark)

    Moustgaard, Helene; Bjerregaard, Peter; Borch-Johnsen, Knut

    2005-01-01

    The study aimed to estimate the prevalence of diabetes and impaired glucose intolerance (IGT) among Inuit migrants living in Denmark, and to compare with findings from Greenland. Further, we analyzed determinants for diabetes and impaired glucose metabolism.......The study aimed to estimate the prevalence of diabetes and impaired glucose intolerance (IGT) among Inuit migrants living in Denmark, and to compare with findings from Greenland. Further, we analyzed determinants for diabetes and impaired glucose metabolism....

  16. A P387L variant in protein tyrosine phosphatase-1B (PTP-1B) is associated with type 2 diabetes and impaired serine phosphorylation of PTP-1B in vitro

    DEFF Research Database (Denmark)

    Echwald, Søren M; Riis, Helle Bach; Vestergaard, Henrik

    2002-01-01

    In the present study, we tested the hypothesis that variability in the protein tyrosine phosphatase-1B (PTP-1B) gene is associated with type 2 diabetes. Using single-strand conformational polymorphism analysis, we examined cDNA of PTP-1B from 56 insulin-resistant patients with type 2 diabetes.......0012). In summary, a rare P387L variant of the PTP-1B gene is associated with a 3.7 (CI 1.26-10.93, P = 0.02) genotype relative risk of type 2 diabetes in the examined population of Danish Caucasian subjects and results in impaired in vitro serine phosphorylation of the PTP-1B peptide....

  17. Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus.

    Science.gov (United States)

    Martinez, Perla J; Mathews, Christine; Actor, Jeffrey K; Hwang, Shen-An; Brown, Eric L; De Santiago, Heather K; Fisher Hoch, Susan P; McCormick, Joseph B; Mirza, Shaper

    2014-01-01

    Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. Patients with diabetes demonstrated a lower frequency of total CD+T-cells, which showed a significant inverse association with elevated fasting blood glucose. Measurement of specific subsets indicated that those with diabetes had, low intracellular levels of interleukin (IL)-17, and lower pathogen-specific memory CD4+ and IL-17+ cell numbers. No significant difference was observed in the frequency of CD4+ and Th17 cells between those with and without diabetes. However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation. Copyright © 2014 Mosby, Inc. All rights reserved.

  18. Diabetes and hypertension in urban bhutanese men and women

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    Bhakta Raj Giri

    2013-01-01

    Full Text Available Background: Bhutan is a mountainous country with 31% urban population. There is no information on prevalence of diabetes and hypertension in Bhutan yet. This was the first study of its kind conducted in the capital city. Objective: To determine prevalence of diabetes, impaired fasting glucose (IFG, impaired glucose tolerance (IGT and hypertension in urban Bhutanese population aged 25 to 74 years. Materials and Methods: Stratified two-stage sampling was adopted to include 2474 respondents (Males: 1132, Females: 1342 equally distributed among different age and sex groups. A questionnaire containing demographic, educational and social details and history of diabetes and hypertension was administered on the sampled population the previous evening and blood pressure measured the next morning in nearby camp where fasting blood samples were collected and an oral glucose tolerance test done. Results: Age and sex standardized prevalence of diabetes, IGT and IFG were 8.2.0, 21.6 and 4%, respectively. Only 66.5% of the population had normal blood sugar. Prevalence of diabetes and IGT increased progressively with increasing age. Prevalence of hypertension was 26% (Males: 28.3%, Females: 23.2%. It was observed that 54.1% of diabetes population had hypertension. Conclusion: The study shows that not only is prevalence of diabetes and hypertension high in the urban Bhutanese but also there is a high diagnosis and treatment gap in these disorders.

  19. Visual Impairment and Blindness Avoided with Ranibizumab in Hispanic and Non-Hispanic Whites with Diabetic Macular Edema in the United States.

    Science.gov (United States)

    Varma, Rohit; Bressler, Neil M; Doan, Quan V; Danese, Mark; Dolan, Chantal M; Lee, Abraham; Turpcu, Adam

    2015-05-01

    To estimate visual impairment (VI) and blindness avoided with intravitreal ranibizumab 0.3 mg treatment for central-involved diabetic macular edema (DME) among Hispanic and non-Hispanic white individuals in the United States. Population-based model simulating visual acuity (VA) outcomes over 2 years after diagnosis and treatment of DME. Visual acuity changes with and without ranibizumab were based on data from the RISE, RIDE, and DRCR Network trials. For the better-seeing eye, VA outcomes included VI, defined as worse than 20/40 in the better-seeing eye, and blindness, defined as VA of 20/200 or worse in the better-seeing eye. Incidence of 1 or both eyes with central-involved DME in 2010 were estimated based on the 2010 United States population, prevalence of diabetes mellitus, and 1-year central-involved DME incidence rate. Sixty-one percent of incident individuals had bilateral DME and 39% had unilateral DME, but DME could develop in the fellow eye. Cases of VI and blindness avoided with ranibizumab treatment. Among approximately 102 million Hispanic and non-Hispanic white individuals in the United States 45 years of age and older in 2010, an estimated 37 274 had central-involved DME and VI eligible for ranibizumab treatment. Compared with no ranibizumab treatment, the model predicted that ranibizumab 0.3 mg every 4 weeks would reduce the number of individuals with VI from 11 438 (95% simulation interval [SI], 7249-16 077) to 6304 (95% SI, 3921-8981), a 45% (95% SI, 36%-53%) reduction at 2 years. Ranibizumab would reduce the number of incident eyes with VA worse than 20/40 from 16 910 (95% SI, 10 729-23 577) to 9361 (95% SI, 5839-13 245), a 45% (95% SI, 38%-51%) reduction. Ranibizumab was estimated to reduce the number of individuals with legal blindness by 75% (95% SI, 58%-88%) and the number of incident eyes with VA of 20/200 or worse by 76% (95% SI, 63%-87%). This model suggests that ranibizumab 0.3 mg every 4 weeks substantially reduces prevalence of VI and

  20. White Matter Hyperintensity in Elderly Patients with Diabetes Mellitus Is Associated with Cognitive Impairment, Functional Disability, and a High Glycoalbumin/Glycohemoglobin Ratio

    Directory of Open Access Journals (Sweden)

    Yoshiaki Tamura

    2017-07-01

    Full Text Available Aims: Although evidence has accumulated that white matter hyperintensity (WMH is associated with the deterioration of cognitive function and impairment of activities of daily living (ADL, the clinical relevance of WMH in elderly patients with diabetes mellitus (DM is not still clear. The aim of this study was to examine whether WMH volume is associated with ADL and cognitive function and whether glucose control and glucose variability can affect WMH volume in these patients.Methods: This cross-sectional study investigated the associations of WMH with cognitive function and instrumental ADL (IADL, as well as metabolic and vascular risk factors in a total of 178 elderly patients with diabetes. The study assessed WMH volumes and the functional status of cognition and IADL. WMH volumes were evaluated by obtaining axial T2-weighted and fluid-attenuated inversion recovery sequence images on brain magnetic resonance imaging and assessing the images using Software for Neuro-Image Processing in Experimental Research.Results: We found a significant association between WMH volumes and Mini-Mental State Examination (MMSE scores (p = 0.039 and between WMH and IADL status (p = 0.006. Furthermore, we found significant relations of large WMH volumes with a high glycoalbumin/glycohemoglobin ratio (GA/HbA1c (p < 0.001. Large WMH volumes were also found to be associated with a low body mass index (p = 0.014 and a low diastolic blood pressure (p = 0.024, but not with HbA1c. Multiple regression analysis showed that high GA/HbA1c, which reflects high glucose variability, was a significant determining factor for large WMH volumes. We also found that GA/HbA1c was negatively associated with both MMSE (p = 0.036 and IADL (p < 0.001.Conclusion: GA/HbA1c, which is a marker of glucose variability, was independently associated with WMH volumes, which could lead to the decline of cognition and IADL in elderly patients with DM.

  1. Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-γ expression in nonobese Type 2 diabetic rats.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Kang, Suna

    2016-01-01

    Human studies have provided relatively strong associations of poor vitamin D status with Type 2 diabetes but do not explain the nature of the association. Here, we explored the physiological pathways that may explain how vitamin D status modulates energy, lipid and glucose metabolisms in nonobese Type 2 diabetic rats. Goto-Kakizaki (GK) rats were fed high-fat diets containing 25 (VD-low), 1000 (VD-normal) or 10,000 (VD-high) cholecalciferol-IU/kg diet for 8 weeks. Energy expenditure, insulin resistance, insulin secretory capacity and lipid metabolism were measured. Serum 25-OH-D levels, an index of vitamin D status, increased dose dependently with dietary vitamin D. VD-low resulted in less fat oxidation without a significant difference in energy expenditure and less lean body mass in the abdomen and legs comparison to the VD-normal group. In comparison to VD-low, VD-normal had lower serum triglycerides and intracellular fat accumulation in the liver and skeletal muscles which was associated with down-regulation of the mRNA expressions of sterol regulatory element binding protein-1c and fatty acid synthase and up-regulation of gene expressions of peroxisome proliferator-activated receptors (PPAR)-α and carnitine palmitoyltransferase-1. In euglycemic hyperinsulinemic clamp, whole-body and hepatic insulin resistance was exacerbated in the VD-low group but not in the VD-normal group, possibly through decreasing hepatic insulin signaling and PPAR-γ expression in the adipocytes. In 3T3-L1 adipocytes 1,25-(OH)2-D (10 nM) increased triglyceride accumulation by elevating PPAR-γ expression and treatment with a PPAR-γ antagonist blocked the triglyceride deposition induced by 1,25-(OH)2-D treatment. VD-low impaired glucose-stimulated insulin secretion in hyperglycemic clamp and decreased β-cell mass by decreasing β-cell proliferation. In conclusion, vitamin D deficiency resulted in the dysregulation of glucose metabolism in GK rats by simultaneously increasing insulin

  2. Gap Resolution

    Energy Technology Data Exchange (ETDEWEB)

    2017-04-25

    Gap Resolution is a software package that was developed to improve Newbler genome assemblies by automating the closure of sequence gaps caused by repetitive regions in the DNA. This is done by performing the follow steps:1) Identify and distribute the data for each gap in sub-projects. 2) Assemble the data associated with each sub-project using a secondary assembler, such as Newbler or PGA. 3) Determine if any gaps are closed after reassembly, and either design fakes (consensus of closed gap) for those that closed or lab experiments for those that require additional data. The software requires as input a genome assembly produce by the Newbler assembler provided by Roche and 454 data containing paired-end reads.

  3. The association between cardiorespiratory fitness and risk of all-cause mortality among women with impaired fasting glucose or undiagnosed diabetes mellitus.

    Science.gov (United States)

    Lyerly, G William; Sui, Xuemei; Lavie, Carl J; Church, Timothy S; Hand, Gregory A; Blair, Steven N

    2009-09-01

    To evaluate the independent and joint associations among cardiorespiratory fitness (CRF), body mass index, and risk of mortality from any cause among women with impaired fasting glucose (IFG) or undiagnosed diabetes mellitus (DM). Female patients (N=3044; mean age, 47.4 years) with IFG or undiagnosed DM completed a maximal exercise treadmill test (between January 26, 1971, and March 21, 2001). The women had no history of a cardiovascular disease event or diagnosed DM at baseline. Cardiorespiratory fitness was defined categorically as low (bottom 20%), moderate (middle 40%), or high (upper 40%) according to previously published Aerobics Center Longitudinal Study guidelines. Body mass index was calculated as the weight in kilograms divided by the height in meters squared (kg/m(2)). During a 16-year follow-up period, 171 deaths occurred. There was an inverse association between CRF and all-cause mortality risk. Women with moderate or high CRF were at lower risk of mortality (moderate CRF, 35% lower; high CRF, 36% lower; P(trend)=.03) than those with low CRF. An exercise capacity lower than 7 metabolic equivalents was associated with a 1.5-fold higher risk of death than an exercise capacity of 9 metabolic equivalents or higher (P(trend)=.05). The multivariate adjusted hazard ratios (HRs), including adjustments for CRF, were higher for heavier patients than for patients of normal weight (overweight patients: HR, 0.86; 95% confidence interval, 0.57-1.30; obese patients: HR, 1.19; 95% confidence interval, 0.70-2.03; P(trend)=.84). Combined analyses showed that women who were overweight or obese and unfit (low CRF) were at more than twice the risk of death than women who were of normal weight and fit (moderate or high CRF). Cardiorespiratory fitness, not body mass index, is a significant predictor of all-cause mortality among women with IFG or undiagnosed DM. Assessing CRF levels provides important prognostic information independent of traditional risk factors.

  4. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

    Directory of Open Access Journals (Sweden)

    de la Monte Suzanne M

    2009-12-01

    Full Text Available Abstract Background The current epidemics of type 2 diabetes mellitus (T2DM, non-alcoholic steatohepatitis (NASH, and Alzheimer's disease (AD all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration. Methods Long Evans rat pups were treated with N-nitrosodiethylamine (NDEA by i.p. Injection, and upon weaning, they were fed with high fat (60%; HFD or low fat (5%; LFD chow for 6 weeks. Rats were evaluated for cognitive impairment, insulin resistance, and neurodegeneration using behavioral, biochemical, molecular, and histological methods. Results NDEA and HFD ± NDEA caused T2DM, NASH, deficits in spatial learning, and neurodegeneration with hepatic and brain insulin and/or IGF resistance, and reductions in tau and choline acetyltransferase levels in the temporal lobe. In addition, pro-ceramide genes, which promote insulin resistance, were increased in livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays, the adverse effects of HFD+NDEA were worse than either treatment alone. Conclusions Environmental and food contaminant exposures to low, sub-mutagenic levels of nitrosamines, together with chronic HFD feeding, function synergistically to promote major insulin resistance diseases including T2DM, NASH, and AD-type neurodegeneration. Steps to minimize human exposure to nitrosamines and consumption of high-fat content foods are needed to quell these costly and devastating epidemics.

  5. Decreased Serum IGF-1/IGFBP-3 Molar Ratio is Associated with Executive Function Behaviors in Type 2 Diabetic Patients with Mild Cognitive Impairment.

    Science.gov (United States)

    Huang, Rong; Wang, Pin; Han, Jing; Xia, Wenqing; Cai, Rongrong; Sun, Haixia; Sun, Jie; Wang, Shaohua

    2015-01-01

    Insulin-like growth factor (IGF)-1, through insulin/IGF-1 signaling pathway, is involved in the pathogenesis of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the association of serum IGF-1 and IGF binding protein (IGFBP)-3 levels with cognition status and to determine whether IGF-1 rs972936 polymorphism is associated with T2DM with mild cognitive impairment (MCI). A total of 150 T2DM patients, 75 satisfying the MCI diagnostic criteria and 75 exhibiting healthy cognition, were enrolled in this study. The cognitive function of the subjects was extensively assessed. Serum IGF-1 and IGFBP-3 levels were measured through enzyme-linked immunosorbent assay; IGF-1/IGFBP-3 molar ratio was calculated. Single nucleotide polymorphisms of the IGF-1-(rs972936) gene were analyzed. Serum IGF-1/IGFBP-3 molar ratio in MCI patients was significantly lower than that in the control group (p = 0.003). Significant negative correlations were found between IGF-1/IGFBP-3 molar ratio and Trail Making Test A and B (TMT-A and TMT-B) scores (p = 0.003; p function. Further multiple step-wise regression analysis revealed that the TMT-A or TMT-B score was significantly associated only with serum IGF-1/IGFBP-3 molar ratio (p = 0.016; p IGF-1 rs972936 polymorphism between MCI and control groups. A low serum IGF-1/IGFBP-3 molar ratio is associated with the pathogenesis of MCI, particularly executive function in T2DM populations. Further investigation with a large population size should be conducted to confirm this observed association.

  6. Health and quality of life outcomes impairment of quality of life in type 2 diabetes mellitus: a cross-sectional study.

    Science.gov (United States)

    Zurita-Cruz, Jessie N; Manuel-Apolinar, Leticia; Arellano-Flores, María Luisa; Gutierrez-Gonzalez, Alejandro; Najera-Ahumada, Alma Gloria; Cisneros-González, Nelly

    2018-05-15

    Type 2 diabetes mellitus (DM2) is a chronic disease, and for treatment to succeed, it is necessary to harmonize the mental health of the patient with the environment, which impacts quality of life and adherence to medical regimens. The objetive of this study is describe the quality of life of patients with DM2 and the factors relates to its modification. This investigation was a cross-sectional study. Patients over 18 years of age with DM2 were selected. The following variables related to quality of life were studied: age, sex, occupation, marital status, years of DM2 evolution, comorbidities and presence of depression (Beck Depression Inventory). Perceived quality of life was measured with a health-related quality of life (HRQoL) scale, the 36-Item Short-Form Survey (SF-36). Patients were classified according to SF-36 HRQoL score ( 76 points). Among the 1394 patients included, the median age was 62 years. Global HRQoL had a median of 50.1 points. Bivariate analysis showed that age, marital status, sex, occupation, comorbidities, duration of DM2 and comorbidities had impacts on HRQoL. The logistic regression model identified age (odds ratio [OR] 1.04) and depression (OR 4.4) as independent factors that influenced overall quality of life. Patients with DM2 have poor HRQoL, which is associated with a high frequency of depression. Older age and the presence of depression impair patient HRQoL. R-2013-781-052. Registered 20 December 2014.

  7. Gap Junctions

    Science.gov (United States)

    Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L.; Verma, Vandana; Delmar, Mario; Holstein-Rathlou, Niels-Henrik

    2013-01-01

    Gap junctions are essential to the function of multicellular animals, which require a high degree of coordination between cells. In vertebrates, gap junctions comprise connexins and currently 21 connexins are known in humans. The functions of gap junctions are highly diverse and include exchange of metabolites and electrical signals between cells, as well as functions, which are apparently unrelated to intercellular communication. Given the diversity of gap junction physiology, regulation of gap junction activity is complex. The structure of the various connexins is known to some extent; and structural rearrangements and intramolecular interactions are important for regulation of channel function. Intercellular coupling is further regulated by the number and activity of channels present in gap junctional plaques. The number of connexins in cell-cell channels is regulated by controlling transcription, translation, trafficking, and degradation; and all of these processes are under strict control. Once in the membrane, channel activity is determined by the conductive properties of the connexin involved, which can be regulated by voltage and chemical gating, as well as a large number of posttranslational modifications. The aim of the present article is to review our current knowledge on the structure, regulation, function, and pharmacology of gap junctions. This will be supported by examples of how different connexins and their regulation act in concert to achieve appropriate physiological control, and how disturbances of connexin function can lead to disease. © 2012 American Physiological Society. Compr Physiol 2:1981-2035, 2012. PMID:23723031

  8. impairs gap junction function causing congenital cataract

    Indian Academy of Sciences (India)

    Navya

    2017-03-24

    Mar 24, 2017 ... ... applied to analyze the expression and subcellular localization of recombinant ... Cx46. The fluorescent localization assay revealed the plaque formation ... composed of six trans-membrane protein subunits called connexins ...

  9. Impaired glucose metabolism among those with and without diagnosed diabetes and mortality: a cohort study using Health Survey for England data.

    Directory of Open Access Journals (Sweden)

    Vanessa L Z Gordon-Dseagu

    Full Text Available The extent that controlled diabetes impacts upon mortality, compared with uncontrolled diabetes, and how pre-diabetes alters mortality risk remain issues requiring clarification.We carried out a cohort study of 22,106 Health Survey for England participants with a HbA1C measurement linked with UK mortality records. We estimated hazard ratios (HRs of all-cause, cancer and cardiovascular disease (CVD mortality and 95% confidence intervals (CI using Cox regression.Average follow-up time was seven years and there were 1,509 deaths within the sample. Compared with the non-diabetic and normoglycaemic group (HbA1C <5.7% [<39 mmol/mol] and did not indicate diabetes, undiagnosed diabetes (HbA1C ≥6.5% [≥48 mmol/mol] and did not indicate diabetes inferred an increased risk of mortality for all-causes (HR 1.40, 1.09-1.80 and CVD (1.99, 1.35-2.94, as did uncontrolled diabetes (diagnosed diabetes and HbA1C ≥6.5% [≥48 mmol/mol] and diabetes with moderately raised HbA1C (diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol]. Those with controlled diabetes (diagnosed diabetes and HbA<5.7% [<39 mmol/mol] had an increased HR in relation to mortality from CVD only. Pre-diabetes (those who did not indicate diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol] was not associated with increased mortality, and raised HbA1C did not appear to have a statistically significant impact upon cancer mortality. Adjustment for BMI and socioeconomic status had a limited impact upon our results. We also found women had a higher all-cause and CVD mortality risk compared with men.We found higher rates of all-cause and CVD mortality among those with raised HbA1C, but not for those with pre-diabetes, compared with those without diabetes. This excess differed by sex and diabetes status. The large number of deaths from cancer and CVD globally suggests that controlling blood glucose levels and policies to prevent hyperglycaemia should be considered public health priorities.

  10. Mythic gaps

    Directory of Open Access Journals (Sweden)

    William Hansen

    2014-11-01

    Full Text Available Different kinds of omissions sometimes occur, or are perceived to occur, in traditional narratives and in tradition-inspired literature. A familiar instance is when a narrator realizes that he or she does not fully remember the story that he or she has begun to tell, and so leaves out part of it, which for listeners may possibly result in an unintelligible narrative. But many instances of narrative gap are not so obvious. From straightforward, objective gaps one can distinguish less-obvious subjective gaps: in many cases narrators do not leave out anything crucial or truly relevant from their exposition, and yet readers perceive gaps and take steps to fill them. The present paper considers four examples of subjective gaps drawn from ancient Greek literature (the Pandora myth, ancient Roman literature (the Pygmalion legend, ancient Hebrew literature (the Joseph legend, and early Christian literature (the Jesus legend. I consider the quite varied ways in which interpreters expand the inherited texts of these stories, such as by devising names, manufacturing motives, creating backstories, and in general filling in biographical ellipses. Finally, I suggest an explanation for the phenomenon of subjective gaps, arguing that, despite their variety, they have a single cause.

  11. Vitamin D and Diabetes

    OpenAIRE

    PITTAS, ANASTASSIOS G.; DAWSON-HUGHES, BESS

    2010-01-01

    On the basis of evidence from animal and human studies, vitamin D has emerged as a potential risk modifier for type 1 and type 2 diabetes (type 1 diabetes and type 2 diabetes). Vitamin D is thought to have both direct (through activation of the vitamin D receptor) and indirect (via regulation of calcium homeostasis) effects on various mechanisms related to the pathophysiology of both types of diabetes, including pancreatic beta cell dysfunction, impaired insulin action and systemic inflammati...

  12. Assessment of Gap between Knowledge and Practices among Type 2 Diabetes Mellitus Patients at a Tertiary-Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    Farzana Saleh

    2016-01-01

    Full Text Available Newly diagnosed type 2 diabetes (T2 DM patients who do not receive diabetes education (DE have average knowledge on DM, and their practices about diabetes need to be improved. This prompted us to evaluate what happens when old diagnosed patients receive DE. The study therefore assessed the association between knowledge and practices in terms of Hemoglobin A1c (HbA1c, body mass index (BMI, and waist circumference (WC among 500 diagnosed T2 DM using a cross-sectional design. An interviewer-administered questionnaire was used for assessing their knowledge. The mean knowledge score of the patients was 15.29 ± 3.6. A significant negative association was found between the knowledge score and the HbA1c level. Age was positively associated with HbA1c and WC. Duration of DM was positively and education was negatively associated with HbA1c. Gender was negatively associated with BMI while income was positively associated with BMI and WC. All the associations were significant. The diagnosed T2 DM patients are deficient of sufficient knowledge; the knowledge score and HbA1c have a significant negative relationship, not other actions. The risk factors for the patients’ outcome include old age, female gender, years of education, economic status, and duration of DM.

  13. Targeting connexin 43 in diabetic wound healing: Future perspectives

    Directory of Open Access Journals (Sweden)

    Bajpai S

    2009-01-01

    Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

  14. Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training

    DEFF Research Database (Denmark)

    Vind, B. F.; Pehmøller, Christian; Treebak, Jonas Thue

    2011-01-01

    AIMS/HYPOTHESIS: Insulin-mediated glucose disposal rates (R (d)) are reduced in type 2 diabetic patients, a process in which intrinsic signalling defects are thought to be involved. Phosphorylation of TBC1 domain family, member 4 (TBC1D4) is at present the most distal insulin receptor signalling...... event linked to glucose transport. In this study, we examined insulin action on site-specific phosphorylation of TBC1D4 and the effect of exercise training on insulin action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic patients. METHODS: During a 3 h euglycaemic-hyperinsulinaemic (80...... mU min(-1) m(-2)) clamp, we obtained M. vastus lateralis biopsies from 13 obese type 2 diabetic and 13 obese, non-diabetic control individuals before and after 10 weeks of endurance exercise-training. RESULTS: Before training, reductions in insulin-stimulated R (d), together with impaired insulin...

  15. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Debmalya Sanyal

    2015-01-01

    Full Text Available Context: The perception of non-alcoholic fatty liver disease (NAFLD as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT, new onset treatment naive T2DM and normal glucose tolerance (NGT with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables, Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT 40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary

  16. Progression from impaired fasting glucose to type 2 diabetes mellitus among Chinese subjects with and without hypertension in a primary care setting.

    Science.gov (United States)

    Fu, Sau Nga; Luk, Wan; Wong, Carlos King Ho; Cheung, Kwok Leung

    2014-09-01

    The progression from impaired fasting glucose (IFG) to type 2 diabetes mellitus (T2DM) in Chinese subjects, with and without hypertension, in a primary care setting was unknown. The present retrospective multicenter 5-year (2002-2007) cohort study was performed on IFG subjects attending 23 general outpatient clinics who were identified by their elevated fasting blood glucose laboratory results. Development of T2DM was determined by physician diagnosis of T2DM or starting of oral antidiabetic drugs within 5 years. The relationship between the time of T2DM diagnosis and subject characteristics was assessed by adjusted hazard ratios (aHR) from Cox hazards model. Of the 9161 IFG subjects, 4080 (45%) were men and 5081 (55%) were women. There were 1998 subjects who developed T2DM. The 5-year cumulative incidence was 0.218, whereas the overall annual incidence rate was 5.981/100 person-years. Subjects were more likely to develop T2DM if they were hypertensive (aHR = 1.44; 95% confidence interval [CI] 1.28-1.62; P < 0.001), aged <60 years (aHR = 1.36, 95% CI 1.24-1.49; P < 0.001), female (aHR = 1.18, 95% CI 1.08-1.29; P < 0.001), and had higher fasting glucose levels (6.39 ± 0.49 vs 6.24 ± 0.43 mmol/L in the group that developed T2DM vs the group without T2DM, respectively; aHR = 2.01, 95% CI 1.83-2.20; P < 0.001). Overall, more than one-fifth of IFG subjects in the primary care setting developed T2DM within 5 years. Health care professionals can target interventions to patients with risk factors for disease progression. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  17. Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function.

    Science.gov (United States)

    Heunisch, Fabian; von Einem, Gina; Alter, Markus; Weist, Andreas; Dschietzig, Thomas; Kretschmer, Axel; Hocher, Berthold

    2014-11-24

    Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91±1.23 pg/ml versus 0.63±1.03 pg/ml, pET-1/creatinine ratio: 0.14±0.23 versus 0.09±0.19, pET-1 concentrations in patients with CIN decreased significantly more than in patients without CIN (-0.26±1.42 pg/ml vs. -0.79±1.69 pg/ml, p=0.041), whereas the decrease of the urinary ET-1/creatinine ratio was not significantly different (non-CIN patients: -0.05±0.30; CIN patients: -0.11±0.21, p=0.223). Urinary ET-1 concentrations as well as the urinary ET-1/creatinine ratio were not associated with clinical events (need for dialysis, rehospitalization or death) during the 90 day follow-up after contrast media exposure. However, the urinary ET-1 concentration and the urinary ET-1/creatinine ratio after CM application were higher in those patients who had a decrease of GFR of at least 25% after 90 days of follow-up. In general the ET-1 system in the kidney seems to be down-regulated after contrast media application in patients with moderate CIN risk. Major long-term complications of CIN (need for dialysis, rehospitalization or death) are not associated with the renal ET system

  18. Cost-effectiveness of ranibizumab versus aflibercept in the treatment of visual impairment due to diabetic macular edema: a UK healthcare perspective

    Directory of Open Access Journals (Sweden)

    Régnier SA

    2015-05-01

    Full Text Available Stephane A Régnier,1 William Malcolm,2 Jennifer Haig,3 Weiguang Xue41Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals UK Ltd, Frimley Business Park, UK; 3Optum, Burlington, ON, Canada; 4Optum, Uxbridge, UKBackground: Ranibizumab and aflibercept are alternative anti-vascular endothelial growth factor agents approved for the treatment of visual impairment (VI due to diabetic macular edema (DME.Objective: To estimate, from a UK healthcare perspective, the cost-effectiveness of ranibizumab 0.5 mg pro re nata (PRN and ranibizumab 0.5 mg treat and extend (T&E compared with aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8 in the treatment of VI due to DME.Methods: A Markov model previously reviewed by the National Institute for Health and Care Excellence was used to simulate the long-term outcomes and costs of treating DME. Health states were defined by increments of ten letters in best-corrected visual acuity (BCVA, with a 3-month cycle length. Patients could gain (or lose a maximum of two health states between cycles. A 3-year treatment time frame and a lifetime horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Patient baseline characteristics and the efficacy of ranibizumab PRN were derived using data from the RESTORE study. The relative efficacies of ranibizumab PRN, ranibizumab T&E, and aflibercept were assessed with a network meta-analysis. Different utilities were assigned based on BCVA and whether the treated eye was the better- or the worse-seeing eye. Sensitivity analyses tested the robustness of the model.Results: Lifetime costs per patient of treating DME were £20,019 for ranibizumab PRN, £22,930 for ranibizumab T&E, and £25,859 for aflibercept 2q8. Ranibizumab was dominant over aflibercept, with an incremental gain of 0.05 quality-adjusted life-years (QALYs and cost savings of £5,841 (PRN and £2,930 (T&E compared with aflibercept. Ranibizumab PRN and

  19. Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial.

    Science.gov (United States)

    Papakonstantinou, E; Kontogianni, M D; Mitrou, P; Magriplis, E; Vassiliadi, D; Nomikos, T; Lambadiari, V; Georgousopoulou, E; Dimitriadis, G

    2018-04-06

    The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D). In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m 2 ), IGT-B (n=20, BMI: 32.5±5kg/m 2 ) or T2D (n=12, BMI: 32.2±5.2kg/m 2 ) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period. Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (Pmeal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (Pweight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. 'I've put diabetes completely on the shelf till the mental stuff is in place'. How patients with doctor-assessed impaired self-care perceive disease, self-care, and support from general practitioners. A qualitative study

    DEFF Research Database (Denmark)

    Kristensen, Mads Aage Toft; Guassora, Ann Dorrit; Arreskov, Anne Beiter

    2018-01-01

    OBJECTIVE: This paper investigated patients' experiences of disease and self-care as well as perceptions of the general practitioner's role in supporting patients with impaired self-care ability. DESIGN: Qualitative interviews with 13 patients with type 2 diabetes, concurrent chronic diseases...... recommendations.   • Shifting emotional aspects were prominent in patients' considerations of disease and sustained GPs' use of a patient-centred clinical method when discussing self-care.   • Relational continuity with general practitioners was a highly valued support and should be prioritized for patients...

  1. [Diabetes insipidus].

    Science.gov (United States)

    Krysiak, Robert; Handzlik-Orlik, Gabriela; Okopień, Bogusław

    2014-01-01

    Diabetes insipidus is an uncommon disorder of water-electrolyte balance characterized by the excretion of abnormally large volumes of diluted urine (polyuria) and increased fluid intake (polydipsia). The disease may result from the insufficient production of vasopressin, its increased degradation, an impaired response of kidneys to vasopressin, or may be secondary to excessive water intake. Patients with severe and uncompensated symptoms may develop marked dehydration, neurologic symptoms and encephalopathy, and therefore diabetes insipidus can be a life-threatening condition if not properly diagnosed and managed. Patients with diabetes insipidus require treatment with desmopressin or drugs increasing sensitivity of the distal nephron to vasopressin, but this treatment may be confusing because of the disorder's variable pathophysiology and side-effects of pharmacotherapy. This review summarizes the current knowledge on different aspects of the pathophysiology, classification, clinical presentation, diagnosis, and management of diabetes insipidus. The reader is also provided with some practical recommendations on dealing with patients suffering from this disease.

  2. Type 2 diabetes models

    DEFF Research Database (Denmark)

    Gram, Dorte Xenia

    2012-01-01

    This chapter deals with type 2 diabetes in vivo models and techniques suitable for testing new anti-diabetic compounds. In particular, the testing of TRP antagonist for beneficial effects against type 2 diabetes is considered. There are many choices of both in vitro techniques and in vivo models......, impaired glucose tolerance, impaired insulin secretion, and insulin resistance in vivo and should, thus, be sufficient to demonstrate preclinical proof of concept of a TRP antagonist in type 2 diabetes in rodents. The experiments are suggestions and could be replaced or supplemented by others....

  3. Non-alcoholic fatty liver disease and impaired proinsulin conversion as newly identified predictors of the long-term non-response to a lifestyle intervention for diabetes prevention: results from the TULIP study.

    Science.gov (United States)

    Schmid, Vera; Wagner, Robert; Sailer, Corinna; Fritsche, Louise; Kantartzis, Konstantinos; Peter, Andreas; Heni, Martin; Häring, Hans-Ulrich; Stefan, Norbert; Fritsche, Andreas

    2017-12-01

    Lifestyle intervention is effective to prevent type 2 diabetes. However, a considerable long-term non-response occurs to a standard lifestyle intervention. We investigated which risk phenotypes at baseline and their changes during the lifestyle intervention predict long-term glycaemic non-response to the intervention. Of 300 participants at high risk for type 2 diabetes who participated in a 24 month lifestyle intervention with diet modification and increased physical activity, 190 participants could be re-examined after 8.7 ± 1.6 years. All individuals underwent a five-point 75 g OGTT and measurements of body fat compartments and liver fat content with MRI and spectroscopy at baseline, 9 and 24 months during the lifestyle intervention, and at long-term follow-up. Fasting proinsulin to insulin conversion (PI/I ratio) and insulin sensitivity and secretion were calculated from the OGTT. Non-response to lifestyle intervention was defined as no decrease in glycaemia, i.e. no decrease in AUC for glucose at 0-120 min during OGTT (AUCglucose 0-120 min ). Before the lifestyle intervention, 56% of participants had normal glucose regulation and 44% individuals had impaired fasting glucose and/or impaired glucose tolerance. At long-term follow-up, 11% had developed diabetes. Multivariable regression analysis with adjustment for age, sex, BMI and change in BMI during the lifestyle intervention revealed that baseline insulin secretion and insulin sensitivity, as well as change in insulin sensitivity during the lifestyle intervention, predicted long-term glycaemic control after 9 years. In addition, increased hepatic lipid content as well as impaired fasting proinsulin conversion at baseline were newly detected phenotypes that independently predicted long-term glycaemic control. Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the

  4. High anion gap metabolic acidosis induced by cumulation of ketones, L- and D-lactate, 5-oxoproline and acute renal failure.

    Science.gov (United States)

    Heireman, Laura; Mahieu, Boris; Helbert, Mark; Uyttenbroeck, Wim; Stroobants, Jan; Piqueur, Marian

    2017-07-27

    Frequent causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis and impaired renal function. In this case report, a HAGMA caused by ketones, L- and D-lactate, acute renal failure as well as 5-oxoproline is discussed. A 69-year-old woman was admitted to the emergency department with lowered consciousness, hyperventilation, diarrhoea and vomiting. The patient had suffered uncontrolled type 2 diabetes mellitus, underwent gastric bypass surgery in the past and was chronically treated with high doses of paracetamol and fosfomycin. Urosepsis was diagnosed, whilst laboratory analysis of serum bicarbonate concentration and calculation of the anion gap indicated a  HAGMA. L-lactate, D-lactate, β-hydroxybutyric acid, acetone and 5-oxoproline serum levels were markedly elevated and renal function was impaired. We concluded that this case of HAGMA was induced by a variety of underlying conditions: sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion and paracetamol intake. Risk factors for 5-oxoproline intoxication present in this case are female gender, sepsis, impaired renal function and uncontrolled type 2 diabetes mellitus. Furthermore, chronic antibiotic treatment with fosfomycin might have played a role in the increased production of 5-oxoproline. Paracetamol-induced 5-oxoproline intoxication should be considered as a cause of HAGMA in patients with female gender, sepsis, impaired renal function or uncontrolled type 2 diabetes mellitus, even when other more obvious causes of HAGMA such as lactate, ketones or renal failure can be identified.

  5. Knowledge Gaps

    DEFF Research Database (Denmark)

    Lyles, Marjorie; Pedersen, Torben; Petersen, Bent

    2003-01-01

    The study explores what factors influence the reduction of managers' perceivedknowledge gaps in the context of the environments of foreign markets. Potentialdeterminants are derived from traditional internationalization theory as well asorganizational learning theory, including the concept...... of absorptive capacity. Building onthese literature streams a conceptual model is developed and tested on a set of primarydata of Danish firms and their foreign market operations. The empirical study suggeststhat the factors that pertain to the absorptive capacity concept - capabilities ofrecognizing......, assimilating, and utilizing knowledge - are crucial determinants ofknowledge gap elimination. In contrast, the two factors deemed essential in traditionalinternationalization process theory - elapsed time of operations and experientiallearning - are found to have no or limited effect.Key words...

  6. Retinopathy is associated with impaired myocardial function assessed by advanced echocardiography in type 1 diabetes patients – The Thousand & 1 Study

    DEFF Research Database (Denmark)

    Nouhravesh, Nina; Andersen, Henrik U; Jensen, Jan S

    2016-01-01

    AIMS: Retinopathy and heart disease in Type 1 Diabetes Mellitus (Type 1 DM) may be associated; however previous results have been conflicting. Tissue Doppler Imaging (TDI) and speckle-tracking echocardiography (STE) quantify myocardial function not assessable by conventional echocardiography. We...... investigated the association between severity of retinopathy and early myocardial dysfunction using conventional echocardiography, TDI and STE in Type 1 DM patients. METHODS: Type 1 Diabetes Mellitus patients without known heart disease were included from the Steno Diabetes Center. The cross sectional...... association between retinopathy and myocardial function was analyzed in uni-and multivariable models. Retinopathy was categorized as nil-, simplex- or proliferative retinopathy. RESULTS: A total of 1090 Type 1 Diabetes Mellitus patients were included, mean age was 49.6years and 53% were males. Left...

  7. Relative contributions of energy expenditure on physical activity, body composition and weight gain to the evolution of impaired glucose tolerance to Frank diabetes

    International Nuclear Information System (INIS)

    Forrester, T.; Wilks, R.; Jahoor, F.; Adeyemo, A.

    1999-01-01

    In modem technological societies the requirement for physical work is diminished and access to food is unrestricted. Under these circumstances a large proportion of the population will gain weight and develop obesity and diabetes. At the individual level, genetic and behavioural factors must combine to lead to an imbalance between energy intake and its expenditure. Weight gain, especially rapid weight gain in a population appears to increase the risk of diabetes sharply. Thus understanding the route to weight gain and obesity, and the modulatory effects of physical activity on development of glucose intolerance is critical to credible intervention strategies to reverse or prevent diabetes in populations especially those in transitional societies. In this proposal we will examine the quantitative importance of non-resting energy expenditure (EE) in populations with rising levels of obesity and high prevalence of diabetes. (author)

  8. The prevalence of impaired fasting glucose and undiagnosed diabetes mellitus and associated risk factors among adults living in a rural Koladiba town, northwest Ethiopia

    OpenAIRE

    Worede, Abebaw; Alemu, Shitaye; Gelaw, Yalemzewod Assefa; Abebe, Molla

    2017-01-01

    Background Diabetes mellitus is becoming a big public health challenge, particularly in developing countries like Ethiopia. It is a manageable disease if early screening and follow up is made. However, as studies in Ethiopia are limited and unorganized, determining the magnitude of prediabetes and diabetes and identifying associated risk factors is quite essential. Methods A community-based, cross-sectional study was conducted from February to April 2015 among adults (aged ?20?years) in a rur...

  9. A self-assessment predictive model for type 2 diabetes or impaired fasting glycaemia derived from a population-based survey.

    Science.gov (United States)

    Asadollahi, Khairollah; Asadollahi, Parisa; Azizi, Monire; Abangah, Ghobad

    2017-09-01

    There is no cure for diabetes and its prevention is interesting for both people and health policy makers. The aim of this study was to construct a simple scoring system to predict diabetes and suggest a self assessment predictive model for type 2 diabetes in Iran. This study was a part of a comprehensive population based survey performed in Ilam province during 2011-2012, including 2158 cases≥25years. All demographic and laboratory results were entered into the prepared sheets and were analysed using SPSS 16. By identification of relative risks of diabetes and IFG, a predictive model was constructed and proposed for these abnormalities. Totally, 2158 people comprising 72% female, 60% from urban regions, mean age of 45.5±14years were investigated and the average height, weight, FBS and waist of participants were as follows respectively: 164±8.9cm, 68.4±12.3kg, 5.7±2.8mmol/l (102.6±49.9mg/dl) and 82.3±14.3cm. The prevalence of IFG, diabetes and hyperglycaemia among all participants were 7.8%, 11.8% and 19.6% respectively. Regression analysis revealed familial history of diabetes, place of life, age, hypertension, daily exercise, marital status, gender, waist size, smoking, and BMI as the most relevant risk factors for diabetes and hyperglycemia. A self-assessment predictive model was constructed for general population living in the west of Iran. This is the first self-assessment predictive model for diabetes in Iran. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Li, Ruifei; Wang, Rui; Li, Haixia; Sun, Sihao; Zou, Meijuan; Cheng, Gang

    2016-09-01

    To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta-analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2 diabetes mellitus patients with renal impairment was performed. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched through the end of March 2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were compared with a placebo or other active-comparators, (2) the treatment duration was ≥12 weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ), changes in fasting plasma glucose or hypoglycaemia and other adverse events were reported. Of 790 studies, ten studies on eight randomized clinical trials were included. Compared with the control group, DPP-4 inhibitors were associated with a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45, 95% confidence intervals (-0.57, -0.33), p 1] and long-term [MD = -0.33, 95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long-term greater reduction in HbA1c with DPP-4 inhibitor treatment was only significant when the control treatment comprised placebo plus stable background treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95% confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however, this effect was not present over the long-term. Regarding the hypoglycaemia adverse events assessment, the long-term treatment data indicated there was no increased risk of hypoglycaemia compared with placebo or active-controlled anti-diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are effective and equivalent to other agents in type 2 diabetes mellitus patients with renal impairment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015

  11. High prevalence of type 2 diabetes and pre-diabetes in adult offspring of women with gestational diabetes mellitus or type 1 diabetes: the role of intrauterine hyperglycemia

    DEFF Research Database (Denmark)

    Clausen, Tine D; Mathiesen, Elisabeth R; Hansen, Torben

    2008-01-01

    the background population (O-BP). RESULTS: The prevalence of type 2 diabetes and pre-diabetes (impaired glucose tolerance or impaired fasting glucose) in the four groups was 21, 12, 11, and 4%, respectively. In multiple logistic regression analysis, the adjusted odds ratios (ORs) for type 2 diabetes...

  12. Mitochondrial dysfunction and apoptosis in cumulus cells of type I diabetic mice.

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2010-12-01

    Full Text Available Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females.

  13. Diabetic microangiopathy: impact of impaired cerebral vasoreactivity and delayed angiogenesis after permanent middle cerebral artery occlusion on stroke damage and cerebral repair in mice.

    Science.gov (United States)

    Poittevin, Marine; Bonnin, Philippe; Pimpie, Cynthia; Rivière, Léa; Sebrié, Catherine; Dohan, Anthony; Pocard, Marc; Charriaut-Marlangue, Christiane; Kubis, Nathalie

    2015-03-01

    Diabetes increases the risk of stroke by three, increases related mortality, and delays recovery. We aimed to characterize functional and structural alterations in cerebral microvasculature before and after experimental cerebral ischemia in a mouse model of type 1 diabetes. We hypothesized that preexisting brain microvascular disease in patients with diabetes might partly explain increased stroke severity and impact on outcome. Diabetes was induced in 4-week-old C57Bl/6J mice by intraperitoneal injections of streptozotocin (60 mg/kg). After 8 weeks of diabetes, the vasoreactivity of the neurovascular network to CO2 was abolished and was not reversed by nitric oxide (NO) donor administration; endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) mRNA, phospho-eNOS protein, nNOS, and phospho-nNOS protein were significantly decreased; angiogenic and vessel maturation factors (vascular endothelial growth factor a [VEGFa], angiopoietin 1 (Ang1), Ang2, transforming growth factor-β [TGF-β], and platelet-derived growth factor-β [PDGF-β]) and blood-brain barrier (BBB) occludin and zona occludens 1 (ZO-1) expression were significantly decreased; and microvessel density was increased without changes in ultrastructural imaging. After permanent focal cerebral ischemia induction, infarct volume and neurological deficit were significantly increased at D1 and D7, and neuronal death (TUNEL+ / NeuN+ cells) and BBB permeability (extravasation of Evans blue) at D1. At D7, CD31+ / Ki67+ double-immunolabeled cells and VEGFa and Ang2 expression were significantly increased, indicating delayed angiogenesis. We show that cerebral microangiopathy thus partly explains stroke severity in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  14. Diabetes screening in the workplace.

    Science.gov (United States)

    Gulley, Tauna; Boggs, Dusta; Mullins, Rebecca; Brock, Emily

    2014-11-01

    The prevalence of diabetes has increased worldwide and the pathophysiological problems associated with diabetes increase the potential for employees' physical disabilities. These complications, including neuropathy, nephropathy, and visual impairment, negatively impact the job performance of employees and compromise workplace safety. Occupational health nurses can provide diabetes screening programs to employees and identify chronic disease risk factors early. This article describes an occupational diabetes screening program at a major corporation in Belize, Central America, defines diabetes, outlines the diabetes teaching plan, and presents the demographics of the participants and results of the screening. Cultural considerations and recommendations for future occupational diabetes screenings are proposed. Copyright 2014, SLACK Incorporated.

  15. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

    2016-11-01

    Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Eva-Maria D; Hansen, Lars; Carstensen, Bendix

    2003-01-01

    .013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion......The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum...... 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0...

  17. Obesity and Diabetes

    OpenAIRE

    Riobó Serván, Pilar

    2013-01-01

    Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion and its possible long term complications. Its pathogenesis is poorly understood, but both genetic and environmental factors, such as obesity and aging, play a key role. "Diabesity" is a new term which refers to diabetes occurring in the context of obesity. In this article, we will discuss the epidemiology and impact of diabetes and obesity and will also outline the comp...

  18. Impaired hormonal counterregulation to biochemical hypoglycaemia does not explain the high incidence of severe hypoglycaemia during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger; Boomsma, Frans

    2013-01-01

    Abstract Aims. To explore hormonal counterregulation to biochemical hypoglycaemia during pregnancy. Methods. Observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years (range 1-36), HbA1c 6.6% (4.9-10.5) in early pregnancy) and 22 healthy pregnant women...... hypoglycaemia (requiring help from another person) was recorded prospectively. Results. During normoglycaemia (serum glucose > 3.9 mmol/L), adrenaline concentrations were higher in early pregnancy compared with late pregnancy in women with diabetes (21 (7-111) pg/ml vs. 17 (2-131), p = 0.02) and healthy women.......35). Noradrenaline, glucagon and cortisol concentrations did not increase during biochemical hypoglycaemia. Conclusion. Adrenaline response to biochemical hypoglycaemia was present at similar levels in early and late pregnancy, particularly in shorter diabetes duration, and was not associated with severe...

  19. Cell motility in models of wounded human skin is improved by Gap27 despite raised glucose, insulin and IGFBP-5

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Catherine S.; Berends, Rebecca F. [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom); Flint, David J. [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE (United Kingdom); Martin, Patricia E.M., E-mail: Patricia.Martin@gcu.ac.uk [Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, 70 Cowcaddens Road, Glasgow G4 0BA (United Kingdom)

    2013-02-15

    Reducing Cx43 expression stimulates skin wound healing. This is mimicked in models when Cx43 function is blocked by the connexin mimetic peptide Gap27. IGF-I also stimulates wound healing with IGFBP-5 attenuating its actions. Further, the IGF-I to IGFBP-5 ratio is altered in diabetic skin, where wound closure is impaired. We investigated whether Gap27 remains effective in augmenting scrape-wound closure in human skin wound models simulating diabetes-induced changes, using culture conditions with raised glucose, insulin and IGFBP-5. Gap27 increased scrape-wound closure in normal glucose and insulin (NGI) and to a lesser extent in high glucose and insulin (HGI). IGF-I enhanced scrape-wound closure in keratinocytes whereas IGFBP-5 inhibited this response. Gap27 overcame the inhibitory effects of IGFBP-5 on IGF-I activity. Connexin-mediated communication (CMC) was reduced in HGI, despite raised Cx43, and Gap27 significantly decreased CMC in NGI and HGI. IGF-I and IGFBP-5 did not affect CMC. IGF-I increased keratinocyte proliferation in NGI, and Gap27 increased proliferation in NGI to a greater extent than in HGI. We conclude that IGF-I and Gap27 stimulate scrape-wound closure by independent mechanisms with Gap27 inhibiting Cx43 function. Gap27 can enhance wound closure in diabetic conditions, irrespective of the IGF-I:IGFBP-5 balance. - Highlights: ► Human organotypic and keratinocyte ‘diabetic’ skin models were used to demonstrate the ability of Gap27 to improve scrape-wound closure. ► Gap27 enhanced scrape-wound closure by reducing Cx43-mediated communication, whereas IGFBP-5 retarded cell migration. ► IGF-I and IGFBP-5 did not affect connexin-mediated pathways. ► Gap27 can override altered glucose, insulin, IGF-I, and IGFBP-5 in ‘diabetic’ skin models and thus has therapeutic potential.

  20. Increase in homeostasis model assessment of insulin resistance (HOMA-IR) had a strong impact on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion: the Saku study.

    Science.gov (United States)

    Morimoto, Akiko; Tatsumi, Yukako; Soyano, Fumie; Miyamatsu, Naomi; Sonoda, Nao; Godai, Kayo; Ohno, Yuko; Noda, Mitsuhiko; Deura, Kijyo

    2014-01-01

    Our aim was to assess the impact of increase in homeostasis model assessment of insulin resistance (HOMA-IR) on the development of type 2 diabetes in Japanese individuals with impaired insulin secretion (IIS). This study included 2,209 participants aged 30-69 without diabetes at baseline who underwent comprehensive medical check-ups between April 2006 and March 2007 at Saku Central Hospital. Participants were classified into eight groups according to the combination of baseline IIS status (non-IIS and IIS) and category of HOMA-IR change between the baseline and follow-up examinations (decrease, no change/small increase, moderate increase, and large increase). Type 2 diabetes was determined from fasting and 2 h post-load plasma glucose concentrations at the follow-up examination between April 2009 and March 2011. At baseline, 669 individuals (30.3%) were classified as having IIS. At follow-up, 74 individuals developed type 2 diabetes. After adjusting for confounding factors including baseline HOMA-IR values, the multivariable-adjusted odds ratios (95% confidence intervals) for type 2 diabetes in the non-IIS with a decrease (mean change in HOMA-IR: -0.47), non-IIS with a moderate increase (mean change in HOMA-IR: 0.28), non-IIS with a large increase (mean change in HOMA-IR: 0.83), IIS with a decrease (mean change in HOMA-IR: -0.36), IIS with no change/small increase (mean change in HOMA-IR: 0.08), IIS with a moderate increase (mean change in HOMA-IR: 0.27), and IIS with a large increase (mean change in HOMA-IR: 0.73) groups, relative to the non-IIS with no change/small increase (mean change in HOMA-IR: 0.08) group were 0.23 (0.04, 1.11), 1.22 (0.26, 5.72), 2.01 (0.70, 6.46), 1.37 (0.32, 4.28), 3.60 (0.83, 15.57), 5.24 (1.34, 20.52), and 7.01 (1.75, 24.18), respectively. Moderate and large increases in HOMA-IR had a strong impact on the development of type 2 diabetes among individuals with IIS in this Japanese population.

  1. Impaired autoregulation of blood flow in skeletal muscle and subcutaneous tissue in long-term Type 1 (insulin-dependent) diabetic patients with microangiopathy

    DEFF Research Database (Denmark)

    Faris, I; Vagn Nielsen, H; Henriksen, O

    1983-01-01

    Autoregulation of blood flow was studied in skeletal muscle and subcutaneous tissue in seven Type 1 (insulin-dependent) diabetic patients (median age: 36 years) with nephropathy and retinopathy and in eight normal subjects of the same age. Blood flow was measured by the local 133Xe washout...... technique. Reduction in arterial perfusion pressure was produced by elevating the limb 20 and 40 cm above heart level. Blood flow remained within 10% of control values when the limb was elevated in normal subjects. In five of the seven diabetic subjects blood flow fell significantly in both tissues when...

  2. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

    Science.gov (United States)

    Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

    2016-06-01

    What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

  3. Overexpression of the ped/pea-15 Gene Causes Diabetes by Impairing Glucose-Stimulated Insulin Secretion in Addition to Insulin Action

    OpenAIRE

    Vigliotta, Giovanni; Miele, Claudia; Santopietro, Stefania; Portella, Giuseppe; Perfetti, Anna; Maitan, Maria Alessandra; Cassese, Angela; Oriente, Francesco; Trencia, Alessandra; Fiory, Francesca; Romano, Chiara; Tiveron, Cecilia; Tatangelo, Laura; Troncone, Giancarlo; Formisano, Pietro

    2004-01-01

    Overexpression of the ped/pea-15 gene is a common feature of type 2 diabetes. In the present work, we show that transgenic mice ubiquitously overexpressing ped/pea-15 exhibited mildly elevated random-fed blood glucose levels and decreased glucose tolerance. Treatment with a 60% fat diet led ped/pea-15 transgenic mice to develop diabetes. Consistent with insulin resistance in these mice, insulin administration reduced glucose levels by only 35% after 45 min, compared to 70% in control mice. In...

  4. Altered Polarization, Morphology, and Impaired Innate Immunity Germane to Resident Peritoneal Macrophages in Mice with Long-Term Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Hui-Fang Liu

    2012-01-01

    Full Text Available Type 2 diabetes (T2D is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time.

  5. The prevalence of depressive symptoms in a white European and South Asian population with impaired glucose regulation and screen-detected Type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Aujla, N.; Skinner, T. C.; Khunti, K.

    2010-01-01

    Aims To compare the identification of prevalent depressive symptoms by the World Health Organization-5 Wellbeing Index (WHO-5) and Centre for Epidemiological Studies Depression Scale (CES-D) for South Asian and white European people, male and female, attending a diabetes screening programme, and ...

  6. Using Patient-Level Data to Develop Meaningful Cross-Trial Comparisons of Visual Impairment in Individuals with Diabetic Macular Edema

    DEFF Research Database (Denmark)

    Sivaprasad, Sobha; Regnier, Stephane A; Fajnkuchen, Franck

    2016-01-01

    INTRODUCTION: The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations. METHODS: A model was created with patient-level data from the RESPOND...

  7. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Science.gov (United States)

    Lotta, Luca A; Scott, Robert A; Sharp, Stephen J; Burgess, Stephen; Luan, Jian'an; Tillin, Therese; Schmidt, Amand F; Imamura, Fumiaki; Stewart, Isobel D; Perry, John R B; Marney, Luke; Koulman, Albert; Karoly, Edward D; Forouhi, Nita G; Sjögren, Rasmus J O; Näslund, Erik; Zierath, Juleen R; Krook, Anna; Savage, David B; Griffin, Julian L; Chaturvedi, Nishi; Hingorani, Aroon D; Khaw, Kay-Tee; Barroso, Inês; McCarthy, Mark I; O'Rahilly, Stephen; Wareham, Nicholas J; Langenberg, Claudia

    2016-11-01

    Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8) for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6) for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the aetiology of type 2 diabetes.

  8. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

    Science.gov (United States)

    Lotta, Luca A.; Scott, Robert A.; Luan, Jian’an; Tillin, Therese; Stewart, Isobel D.; Perry, John R. B.; Karoly, Edward D.; Forouhi, Nita G.; Zierath, Juleen R.; Savage, David B.; Griffin, Julian L.; Hingorani, Aroon D.; Khaw, Kay-Tee; O’Rahilly, Stephen; Langenberg, Claudia

    2016-01-01

    Background Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p branched-chain alpha-ketoacid dehydrogenase (BCKD) responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26–1.65, p = 9.5 × 10−8) for isoleucine, 1.85 (95% CI 1.41–2.42, p = 7.3 × 10−6) for leucine, and 1.54 (95% CI 1.28–1.84, p = 4.2 × 10−6) for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are implicated in type 2 diabetes. Conclusions Evidence from this large-scale human genetic and metabolomic study is consistent with a causal role of BCAA metabolism in the

  9. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Directory of Open Access Journals (Sweden)

    Luca A Lotta

    2016-11-01

    Full Text Available Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8. The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25, encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8 for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6 for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6 for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are

  10. Comparative Analysis of Angiogenic Gene Expression in Normal and Impaired Wound Healing in Diabetic Mice: Effects of Extracorporeal Shock Wave Therapy

    Science.gov (United States)

    2010-01-01

    an impaired wound was able to tum-on and/or augment for a prolonged period a number of key proangiogenic genes which were previously silent , and...Lania G, Zhang Z, Huynh T et al (2009) Early thyroid devel- opment requires a Tbxl-Fgf8 pathway. Dev Bioi 328(1