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  1. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

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    Bell Jimmy D

    2009-04-01

    Full Text Available Abstract The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest

  2. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

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    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  3. Prevalence and Clinical Predictors of Insulin Resistance in Reproductive-Aged Thai Women with Polycystic Ovary Syndrome

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    Thanyarat Wongwananuruk

    2012-01-01

    Full Text Available Objectives. To determine the prevalence of insulin resistance (IR and its predictors in reproductive-aged Thai women with polycystic ovary syndrome (PCOS. Methods. A cross-sectional study was conducted from May 2007 to January 2009. Participants were 250 Thai women with PCOS. Information regarding medical history and physical examination and results of 75 gram OGTT were recorded. Results. The overall prevalence of IR was 20.0%, comprising the prevalence of impaired fasting glucose, impaired glucose tolerance, and diabetic mellitus of 3.2%, 13.6%, and 5.6%, respectively. Multiple logistic regression analysis showed that the independent predictors for IR were age of ≥30 years old, waist circumference (WC of ≥80 cm, presence of acanthosis nigricans (AN, and dyslipidemia with odds ratios (95% confidence interval of 2.14 (1.01–4.52, 3.53 (1.28–9.75, 2.63 (1.17–5.88, and 3.07 (1.16–8.11, respectively. Conclusion. The overall prevalence of IR in reproductive-aged Thai women with PCOS is 20.0%. Age ≥30 years old, WC ≥80 cm, the presence of AN, and dyslipidemia are the significant clinical predictors.

  4. Metabolic syndrome and insulin resistance in obese adolescents

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    Amanda Oliva Gobato

    2014-03-01

    Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  5. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

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    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

  6. Insulin resistance (metabolic) syndrome in children.

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    Rosenberg, B; Moran, A; Sinaiko, A R

    2005-12-01

    The insulin resistance (metabolic) syndrome (IRS), also known as syndrome X, is characterized by a clustering of factors associated with cardiovascular risk (obesity, impaired glucose metabolism, hypertension, and dyslipidemia). As reported from the third National Health and Nutrition Examination survey, the IRS is present in approximately 24% of adults in the United States and is strongly associated with coronary heart disease, stroke, type 2 diabetes, and all-cause mortality. Of equal importance, it is now clear that the origins of the IRS extend back into childhood (the IRS is found in approximately 4-10% of children and adolescents) and that the high prevalence of adult IRS is strongly linked to the development of cardiovascular risk during childhood and tracking of the components of the IRS into adulthood. The goal of this review is to present a summary of the currently available information on the IRS in the pre-adult age group with reference to adult studies only when necessary for clarification. The review will specifically summarize insulin resistance in childhood; the important influence of obesity and, in particular, visceral fat, on insulin resistance and the IRS; differences between ethnic groups; relations to adipocytokines, inflammatory factors and oxidative stress; relations of hypertension and lipids to insulin resistance; familial factors; endocrine complications; and potential therapeutic effects from diet and physical activity. Despite the lesser amount of basic and clinical information on childhood IRS in comparison to information available from adult studies, there can now be little doubt that the adverse associations among risk factors comprising the IRS begin in childhood. The challenge is to identify etiologic relations and develop intervention strategies designed to reduce the increasing prevalence of type 2 diabetes and cardiovascular disease.

  7. New markers of insulin resistance in polycystic ovary syndrome

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    Polak, K.; Czyzyk, A.; Simoncini, T.; Meczekalski, B.

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder in women of reproductive age. The diagnostic criteria include two out of three features: hyperandrogenism, polycystic ovaries on ultrasound and menstrual irregularities (Rotterdam Criteria 2003). PCOS patients are more vulnerable to develop diabetes, cardiovascular diseases and metabolic syndrome. Insulin resistance (IR) is prevalent in women with PCOS independently of obesity and is critically involved in reprod...

  8. Lysosomal proteolysis: effects of aging and insulin.

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    Gromakova, I A; Konovalenko, O A

    2003-07-01

    Age-related characteristics of the effect of insulin on the activity of lysosomal proteolytic enzymes were studied. The relationship between the insulin effect on protein degradation and insulin degradation was analyzed. The effect of insulin on the activities of lysosomal enzymes was opposite in young and old rats (inhibitory in 3-month-old and stimulatory in 24-month-old animals). The activities of proteolytic enzymes were regulated by insulin in a glucose-independent manner: similar hypoglycemic effects of insulin in animals of different ages were accompanied by opposite changes in the activities of lysosomal enzymes. The inhibition of lysosomal enzymes by insulin in 3-month-old rats is consistent with a notion on the inhibitory effect of insulin on protein degradation. An opposite insulin effect in 24-month-old rats (i.e., stimulation of proteolytic activity by insulin) may be partly associated with attenuation of the degradation of insulin, resulting in disturbances in signaling that mediates the regulatory effects of insulin on protein degradation.

  9. Metabolic Syndrome in Estonia: Prevalence and Associations with Insulin Resistance

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    Triin Eglit

    2012-01-01

    Full Text Available Recently, it has been suggested that metabolic syndrome should be considered a premorbid condition in younger individuals. We evaluated the prevalence of metabolic syndrome in Estonia and compared the characteristic profiles between morbid metabolic syndrome (previously established diabetes, hypertension, or dyslipidaemia and premorbid metabolic syndrome subgroups. Our study was a cross-sectional, population-based sample of the general population in Estonia aged 20–74 years (n=495. Metabolic syndrome was diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria. Insulin resistance was estimated using the homeostasis model assessment (HOMA-IR. The crude and weighted prevalence of metabolic syndrome was 27.9% and 25.9%, respectively. Despite being significantly younger, the premorbid subgroup showed similar levels of insulin resistance as the morbid subgroup (mean HOMA-IR ± SD 2.73±1.8 versus 2.97±2.1, P=0.5. The most important attribute of metabolic syndrome is insulin resistance, which already characterises metabolic syndrome in the early stages of its metabolic abnormalities.

  10. Indexes of Insulin Resistance in Hyperinsulinemic Polycystic Ovary Syndrome in a Macedonian Cohort of Women of Reproductive Age: A Cross-Sectional Study

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    Jovanovska-Mishevska, Sasha; Atanasova-Boshku, Aleksandra; Bitoska, Iskra; Ahmeti, Irfan; Todorova, Biljana; Pemovska, Gordana; Milenkovic, Tatjana; Krstevska, Brankica

    2016-01-01

    BACKGROUND: Polycystic ovary syndrome (PCOS) is complex hormonal, metabolic and reproductive disorder and is a leading cause of female infertility. Hyperinsulinemia secondary to insulin resistance plays important role in the pathogenesis of PCOS. AIM: To assess the sensitivity of different indices of insulin resistance and their relevance in a clinical setting. MATERIAL AND METHODS: A cross-sectional study of 43 patients with PCOS and 29 noromo ovulatory women as a control group was conducted. Standard clinical, anthropometrical and hormonal testing for hyperandrogenism was conducted, as well as oral glucose tolerance test with determination of basal and stimulated glucose and insulin values. RESULTS: The dynamic I/G index showed the highest sensitivity and specificity, but the static indexes HOMA-IR and QUICKI, although based on only basal glycemic and insulinemic values, showed good sensitivity, 90.38% and 94.01% respectively. HOMA-IR showed significant positive correlation with the stimulated insulin values. CONCLUSIONS: Our results support the use of static indexes in the evaluation of insulin resistance in women with PCOS in a clinical setting, offering a simple assessment of insulin resistance in PCOS, which holds great prognostic and treatment implications. PMID:28028399

  11. Race and the insulin resistance syndrome.

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    Kramer, Holly; Dugas, Lara; Rosas, Sylvia E

    2013-09-01

    Type 2 diabetes remains an important cause of morbidity and mortality. The metabolic syndrome affects 25% of the adult US population based on the Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults from the National Cholesterol Education Program. Knowledge on the impact of obesity on metabolic health parameters has increased greatly over the past decade. This review discusses the limitations of the National Cholesterol Education Program metabolic syndrome definition and the racial disparities in the clinical presentation of the insulin resistance syndrome. We also examine the current literature with particular emphasis on albuminuria, nonalcoholic fatty liver disease, and intramyocellular lipid content. This review explores potential environmental and genetic reasons for differences in the manifestation of insulin resistance across racial/ethnic groups and highlights several promising areas for further study.

  12. Surrogate Measures of Insulin Resistance in Middle-aged Non-diabetic Subjects

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    Katalin Csép

    2013-12-01

    Full Text Available Objective: Insulin resistance has been shown to be a risk factor for type 2 diabetes and cardiovascular disease. The assessment of insulin sensitivity in the clinical practice, however, faces several difficulties. The study proposes to analyze surrogate measures of insulin resistance based on fasting insulin levels in central Romania, and check whether the diagnosis of the metabolic syndrome is an adequate strategy to identify middle-aged persons with reduced insulin sensitivity. Methods: Anthropometric measurements, metabolic profile, and surrogates measures of insulin sensitivity (GIR, HOMA, QUICKI, FIRI, Belfiore, Bennett, Raynaud, McAuley index based on fasting insulin levels were assessed in 233 non-diabetic middle aged subjects. Results: Cutoff values, determined as the lowest quartile of insulin sensitivity for fasting insulin, HOMA, IRI (1/QUICKI, FIRI and Belfiore's, Bennett's, Raynaud's and McAuley's insulin sensitivity indices were 10.49 mU/L, 2.1, 3.01, 2.32, and 0.03, 1.34, 3.81, 6.29, 5.82. Components of the metabolic syndrome showed moderate but significant correlations with the surrogate measures of insulin resistance (r = 0.22-0.56, p <0.05. HOMA-IR and McAuley indices were the best predictors of clustered cardiometabolic risk factors (AUC - 0.83, 0.81 and 0.82. The metabolic syndrome diagnosis performed well in identifying patients with reduced insulin sensitivity (McAuley 2: sensitivity - 0.78, specificity - 0.84. Conclusion: Fasting insulin derived insulin sensitivity indices may help the recognittion of insulin resistant states predicting cardiometabolic disorders. Actively looking for insulin resistance by these simple indices, or by diagnosing the metabolic syndrome, those at increased risk can be recognized

  13. Melatonin-insulin interactions in patients with metabolic syndrome.

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    Robeva, R; Kirilov, G; Tomova, A; Kumanov, Ph

    2008-01-01

    Metabolic syndrome (MS) as a group of risk factors is strongly associated with diabetes type 2 and cardiovascular disease. Insulin resistance plays a key role in the pathogenesis of MS. Recent studies have shown that melatonin may influence insulin secretion and glucose homeostasis. Therefore, the present study analyzed the relationships between the melatonin and the insulin in patients with MS and controls. The melatonin rhythm, insulin and lipid levels were studied in 40 subjects (21 patients and 19 controls) in reproductive age. The night melatonin-insulin ratio was correlated negatively with low-density lipoprotein cholesterol (r = -0.370, p = 0.024) and total cholesterol (r = -0.348, p = 0.030), and positively with high-density lipoprotein cholesterol levels (r = +0.414, p = 0.010). Night-time melatonin levels were related to night-time insulin concentrations (r = +0.313, p = 0.049). The correlation was pronounced in patients with MS (r = +0.640, p = 0.002), but did not reach statistical significance in controls (P > 0.05). In the patients with MS unlike the controls the night-day melatonin difference (%) correlated negatively with the fasting glucose (r = -0.494, p = 0.023) and positively to daily insulin (r = +0.536, p = 0.012). Our results show that melatonin-insulin interactions may exist in patients with MS, as well as relationships between melatonin-insulin ratio and the lipid profile. Pineal disturbances could influence the pathogenesis and the phenotype variations of the MS. Larger studies are needed to confirm or reject this hypothesis and to clarify the role of the melatonin in the metabolic disturbances.

  14. Insulin sensitivity in chronic pancreatitis and features of insulin resistance syndrome

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    Agnieszka B. Niebisz-Cieślak

    2010-07-01

    Full Text Available INTRODUCTION: Chronic pancreatitis predisposes to diabetes. Loss of endocrine function by β-cells in the Langerhans islets is considered to be the main causative factor, although several studies have also suggested insulin resistance as a possible additional mechanism. OBJECTIVES: The aim of the study was to estimate insulin sensitivity in chronic pancreatitis in view of the coexisting meta bolic syndrome components. PATIENTS AND METHODS: The study involved 30 patients (mean age 50.83 ±6.61 years; 23.33% women, 76.66% men diagnosed with chronic pancreatitis (using imaging tests. Insulin sensitivitywith regard to the coexistent obesity, dyslipidemia, and arterial hypertension was measured using the euglycemic clamp method. RESULTS: Diabetes was present in 22 patients, impaired glucose tolerance in 4, and no carbohydrate metabolism disturbances in 4. Insulin resistance was present in 22 patients (73.33%, in whom a higher prevalence of diabetes (77.27% vs. 62.5% and prediabetes (13.63% vs. 12.5% was observed. The analysis of anthropometric para meters revealed that individuals with a high index of central obesity had a statistically significantly lower tissue glucose utilization (TGU (3.23 vs. 4.89 mg/kg/min; P = 0.02, although there were no obese patients in the study group according to the body mass index. No statistically significant differences in TGU were observed in relation to lipid disorders (total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides and arterial hypertension. CONCLUSIONS: In patients with chronic pancreatitis, lack of correlation between insulin sensitivity and metabolic syndrome components may indicate that insulin resistance is related to primary disease or that an additional mechanism underlying pancreatic diabetes operates.

  15. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

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    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  16. Study of insulin status in metabolic syndrome in correlation with presence of other risk factors

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    Sudhanshu Shekhar; Ram Ranjan Singh; Md. Jawed Akhtar; Vijay Shankar

    2016-01-01

    Background: The metabolic syndrome or insulin resistance syndrome is widely prevalent and multifactorial disorder. The majority of persons with metabolic syndrome have insulin resistance. Insulin resistance and / or associated hyperinsulinemia are believed to be the direct cause of other metabolic syndrome risk factors. The present work is being done to assess the insulin status and to assess the correlation between insulin status and other component of metabolic syndrome. Methods: The pre...

  17. Anthropometric Measures and Fasting Insulin Levels in Children Before and after Cure of Cushing syndrome

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    Keil, Margaret F; Graf, Jennifer; Gokarn, Nirmal; Stratakis, Constantine A

    2011-01-01

    Background & Aims Children with Cushing syndrome present with growth delay and excess adiposity that tends to be generalized rather than centripetal. There are no prospective studies of this phenotype as it evolves before and after treatment in children. The aims of this study were to evaluate children prior to and one-year after surgical cure compared to controls and to determine fasting insulin levels and their possible association with waist circumference and waist-height ratio, pre- and post-cure of Cushing syndrome. Methods 30 children with Cushing syndrome were evaluated prior to and one-year post-treatment and compared to 14 age and body mass index-matched controls. Results Only triceps skin fold z- score showed a significant difference between patients with active Cushing syndrome and controls. A positive correlation between fasting insulin levels and waist circumference z- score was found for children with Cushing syndrome; this association persisted one-year following cure. Conclusions Unlike adults affected with Cushing syndrome, upper arm muscle area of children with Cushing syndrome did not differ from obese children without Cushing syndrome. The persistence of a positive correlation between waist circumference and fasting insulin despite remission of Cushing syndrome suggests that children with a history of Cushing syndrome may have an increased risk for adverse long-term effects of increased abdominal fat mass. Clinical Trial numbers: NCT00001595, NCT00001452, NCT00005927 PMID:22154461

  18. High fasting serum insulin level due to autoantibody interference in insulin immunoassay discloses autoimmune insulin syndrome: a case report.

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    Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric

    2016-08-01

    Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome.

  19. [The role of insulin resistance in diagnosis of metabolic syndrome].

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    Roĭtberg, G E; Ushakova, T I; Dorosh, Zh V

    2004-01-01

    Early diagnosis of metabolic syndrome is based on detection of insulin resistance, hyperinsulinemia, and clinical presentations of this syndrome. Differences in approaches to diagnosis of metabolic syndrome and its multi component nature hamper comparison of results of different studies and elaboration of generalized guidelines for selection of high risk groups and prevention of cardiovascular diseases and type 2 diabetes. Until present there are no common criteria of the syndrome and this makes difficult standardization of methodology of its investigation. Several organizations (WHO, National Cholesterol Education Program, European Group for the Study of Insulin Resistance) issued documents in which diagnostic approaches to detection of metabolic syndrome and its separate components have been formulated. These approaches as well as comparative analysis of direct and calculated methods of assessment of insulin resistance are presented in this review.

  20. Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

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    Manco, Melania; Castagneto-Gissey, Lidia; Arrighi, Eugenio; Carnicelli, Annamaria; Brufani, Claudia; Luciano, Rosa; Mingrone, Geltrude

    2014-01-01

    Background Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. Research Design and Methods Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method). Results Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons). Conclusion Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls. PMID:24705280

  1. Insulin dynamics in young women with polycystic ovary syndrome and normal glucose tolerance across categories of body mass index.

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    Melania Manco

    Full Text Available BACKGROUND: Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS. The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. RESEARCH DESIGN AND METHODS: Sixty-nine cases were divided according to their body mass index (BMI in normal-weight (N = 29, overweight (N = 24 and obese patients (N = 16. Controls were 479 healthy women (age 16-49 y. Whole body Insulin Sensitivity (WBISI, fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method. RESULTS: Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons, but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons. CONCLUSION: Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.

  2. Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

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    C K Indumathi

    2011-01-01

    Full Text Available Berardinelli Seip congenital lipodystrophy (BSCL is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

  3. [Relationship between insulin, leptin, and melatonin contents in patients with metabolic syndrome].

    Science.gov (United States)

    2011-01-01

    Melatonin, leptin, and insulin secretion was studied in 25 men with metabolic syndrome (MS) verified against IDF criteria (2005) (mean age 44 +/- 2 yr). The control group was constituted by 23 healthy men (mean age 45.1 yr). Melatonin secretion was estimated from 6-oxymelatonin sulfate (6-OMS) level in urine samples collected at 4 a.m. (in the darkness). It was shown to increase at this time in both groups but was lower in MS patients than in controls (t = 2, p insulin resistance in patients displaying a peakless melatonin secretion profile is 3 times that in control subjects (OR = 3.0; 95% CI = 1.3-7). It is concluded that patients with MS present with disturbances of melatonin secretion manifest as the absence of its physiological elevation at night hours; they are characterized by negative correlation between melatonin, leptin and insulin levels and changes in melatonin secretion in relation to abnormal production of insulin and leptin.

  4. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

    DEFF Research Database (Denmark)

    Ruzzin, Jérôme; Petersen, Rasmus; Meugnier, Emmanuelle

    2010-01-01

    BACKGROUND: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens...... of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking. OBJECTIVE: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders. METHODS: Wistar rats were exposed...... salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, gene expression and performed microarray analysis. RESULTS: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity...

  5. Association among Fibrinolytic Proteins, Metabolic Syndrome Components, Insulin Secretion, and Resistance in Schoolchildren

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    Jin-Shuen Chen

    2015-01-01

    Full Text Available We investigated the role of urokinase plasminogen activator (uPA and its soluble receptors (suPAR and plasminogen activator inhibitor-1 (PAI-1 in metabolic syndrome (MetS components, insulin secretion, and resistance in schoolchildren. We enrolled 387 children, aged 10.3 ± 1.5 years, in Taipei. Anthropometry, fibrinolytic proteins, MetS components, insulin secretion, and resistance were measured. Subjects were divided into normal, overweight, and obese groups. Finally, the relationship between fibrinolytic proteins and metabolic syndrome in boys and girls was analyzed. In boys, PAI-1 was positively associated with body mass index (BMI percentile, hypertriglyceride, insulin secretion, and resistance. In girls, PAI-1 was positively associated with obesity, hypertriglyceridemia, and insulin secretion. In girls, uPA was positively associated with insulin secretion. suPAR was positively associated with high-sensitivity C-reactive protein in both boys and girls, and with BMI percentile and body fat in girls. The obese boys had higher suPAR and PAI-1 levels than the normal group. The obese girls had higher uPA, suPAR, and PAI-1 than the normal group. Boys and girls with MetS had higher PAI-1. Fibrinolytic proteins, especially PAI-1, are associated with MetS components and insulin secretion in children. Fibrinolytic proteins changes were more likely to occur in girls than in boys.

  6. Study on the Association between Body Weight and Insulin Resistance in Essential Hypertension , X- syndromes and Type- 2 Diabetes

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    王爱玲; 徐岩; 陈森

    2004-01-01

    Objective To prove the hypothesis that there are associations between body weight and insulin resistance in essential hypertension, X- syndromes and type- 2 diabetes. Methods We examined the body mass index (BMI) and insulin sensitve index (ISI) among 70 hypertensives, 39 X - syndromes, 33 type - 2 diabetes and 46 controls. To observe the relations between the degrees of obesity and LSI in all study groups. Seventy patients with hypertension [70 hypertensives, 48 men and 22 women, mean age (69.3 + 6.7) years], 39X-syndromes [27 men and 12 women, mean age (66.4+6.2) years], 33 type- 2 diabetes [21 men and 12 women, mean age (68.7±7.3) years], and 46 healthy controls [36 men and 10 women, mean age (66.1 + 6.6) years]. During study period, no patients died. Results All patients of hypertensives, X - syndromes and type - 2 diabetes have insulin resistance, BMI in all patients was singnificantly higher than in controls. The levels of blood glucose and insulin were significantly higher in obese hypertensives (BMI≥25kg/m2 ) than in those (BMI<25kg/m2 ). LSI in obese subjects with hypertension and X - syndrome were significantly lower than in no - obesities. ISI was related to BMI. Conclusion There were insulin resistance in patients of hypertension and X - syndrome. Obesity was related to lower ISI. Obesity may be an important risk factor for insulin resistance of essential hypertension and X - syndrome. ISI and BMI may be simple and specific clinical predictor for hypertension and X - syndrome patients.

  7. Type 2 diabetes, polycystic ovary syndrome and the insulin resistance syndrome in adolescents: Are they one big iceberg?

    OpenAIRE

    Dean, Heather J.; Sellers, Elizabeth AC

    2002-01-01

    Obesity in children may cause overt clinical disease in childhood. The complex endocrine and metabolic changes of obesity and insulin resistance in adolescents result in hyperinsulinemia, dyslipidemia, hypertension, steatohepatitis, glucose intolerance, type 2 diabetes, acanthosis nigricans and ovarian hyperandrogenemia, commonly known as polycystic ovarian syndrome (PCOS). Type 2 diabetes and PCOS in adolescents are new endocrine diseases in this age group that require unique approaches to d...

  8. Prevalence of insulin resistance and the metabolic syndrome with alternative definitions of impaired fasting glucose.

    Science.gov (United States)

    Ford, Earl S; Abbasi, Fahim; Reaven, Gerald M

    2005-07-01

    We sought to evaluate the effect of the new definition of impaired fasting glucose (IFG = fasting glucose concentration 100-125 mg/dL among people without diabetes) on the ability to identify insulin resistance, as well as the prevalence of the metabolic syndrome in apparently healthy individuals. From the Stanford General Clinical Research Center data-base, we used data from 230 men and 260 women aged 19-79 years who had had an insulin suppression test to measure insulin resistance. From the Third National Health and Nutrition Examination Survey (1988-1994), we used data from 8814 participants aged > or =20 years to estimate the impact of adopting the new IFG criteria on the prevalence of the metabolic syndrome. Among the 490 participants, the prevalence of IFG increased from 5.5% under the old definition of IFG to 20.4% under the new definition. Using the old definition of IFG, the sensitivity, specificity, and positive predictive value (PPV) of IFG of identifying an individual as being insulin resistant were 10%, 97%, and 63%, respectively. Using the new definition, these parameters were 33%, 88%, and 61%, respectively. If the new IFG criteria were adopted, the prevalence of the metabolic syndrome would increase from 21.8% to 26.3%. The new definition of IFG expands the population with insulin resistance by almost four-fold and could expand the population with the metabolic syndrome by about 20%. The clinical and public health implications of the new IFG definition remain to be elucidated.

  9. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

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    Mass-Díaz Eliezer

    2010-06-01

    Full Text Available Abstract Background Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. Methods An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated. Results Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors. Conclusions Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.

  10. Metabolic Syndrome in Estonia: Prevalence and Associations with Insulin Resistance

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    Triin Eglit; Tarvo Rajasalu; Margus Lember

    2012-01-01

    Recently, it has been suggested that metabolic syndrome should be considered a premorbid condition in younger individuals. We evaluated the prevalence of metabolic syndrome in Estonia and compared the characteristic profiles between morbid metabolic syndrome (previously established diabetes, hypertension, or dyslipidaemia) and premorbid metabolic syndrome subgroups. Our study was a cross-sectional, population-based sample of the general population in Estonia aged 20–74 years (n = 495). Metabo...

  11. Growth hormone, insulin and aging: the benefits of endocrine defects.

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    Bartke, Andrzej

    2011-01-01

    Longevity of mice can be increased by spontaneous or experimentally induced mutations that interfere with the biosynthesis or actions of growth hormone (GH), insulin-like growth factor 1 (IGF-1), or insulin in the adipose tissue. The effects of GH resistance and deficiency of GH (along with thyrotropin and prolactin) on aging and lifespan are the most pronounced and best established of these mutations. Potential mechanisms linking these endocrine deficits with delayed aging and extended longevity include increased stress resistance, alterations in insulin and mammalian target of rapamycin (mTOR) signaling and metabolic adjustments. Physiological relationships deduced from the extreme phenotypes of long-lived mouse mutants appear to apply broadly, encompassing genetically normal ("wild-type") mice and other mammalian species. The role of GH in the control of human aging continues to be hotly debated, but recent data indicate that reduced somatotropic signaling provides protection from cancer and other age-related diseases and may promote old age survival.

  12. Beneficial Effects of Ethanol Consumption on Insulin Resistance Are Only Applicable to Subjects Without Obesity or Insulin Resistance; Drinking is not Necessarily a Remedy for Metabolic Syndrome

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    Hirokazu Yokoyama

    2011-07-01

    Full Text Available Although moderate drinking has been shown to lower insulin resistance levels, it is still unclear whether alcoholic beverages could be remedies for insulin resistance. To elucidate this, the correlation between levels of ethanol consumption and insulin resistance were cross-sectionally examined in 371 non-diabetic male Japanese workers. Multiple regression analysis demonstrated that the ethanol consumption level was inversely correlated with the insulin resistance level assessed by homeostatic model assessment (HOMA-IR, p = 0.0014, the serum insulin level (p = 0.0007, and pancreatic β-cell function, also assessed by HOMA (HOMA-β, p = 0.0002, independently from age, body mass index (BMI, and blood pressure, liver function tests, and lipid profiles status, as well as serum adiponectin. The correlations were true in subjects with normal BMIs (up to 25.0 kg/m2, n = 301 or normal HOMA-IR (up to 2.0 µIU·mg/µL·dL n = 337, whereas all of them were non-significant in those with excessive BMIs (n = 70 or in those with HOMA-IR of more than 2.0 (n = 34. Although it is still unclear whether the reductions of these parameters by ethanol consumption are truly due to the improvement of insulin resistance, at least, these effects are not applicable to subjects with obesity and/or insulin resistance. Thus, alcoholic beverages could not be remedies for insulin resistance or metabolic syndrome.

  13. Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Caterina; Arvia; Valeria; Siciliano; Kyriazoula; Chatzianagnostou; Gillian; Laws; Alfredo; Quinones; Galvan; Chiara; Mammini; Sergio; Berti; Sabrina; Molinaro; Giorgio; Iervasi

    2014-01-01

    AIM:To evaluate the impact on glucose variability(GLUCV)of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity.METHODS:We enrolled 44 type 2 diabetic patients(n=32 males;n=12 females)with acute coronary syndrome(ACS)and randomy assigned to standard a subcutaneous insulin treatment(n=23)or a nurse-implemented continuous intravenous insulin infusion protocol(n=21).We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis,i.e.,glucose standard deviation(SD),the mean dailyδglucose(mean of daily difference between maximum and minimum glucose),and the coefficient of variation(CV)of glucose,expressed as percent glucose(SD)/glu-cose(mean).RESULTS:At the admission,first fasting blood glucose,pharmacological treatments(insulin and/or anti-diabetic drugs)prior to entering the study and basal glycated hemoglobin(HbA1c)were observed in the two groups treated with subcutaneous or intravenous insulin infusion,respectively.When compared with patients submitted to standard therapy,insulin-infused patients showed both increased first 24-h(median 6.9 mmol/L vs 5.7mmol/L P<0.045)and overall hospitalizationδglucose(median 10.9 mmol/L vs 9.3 mmol/L,P<0.028),with a tendency to a significant increase in first 24-h glycaemic CV(23.1%vs 19.6%,P<0.053).Severe hypoglycaemia was rare(14.3%),and it was observed only in 3 patients receiving insulin infusion therapy.HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment.CONCLUSION:Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment

  14. Adrenomedullin: possible predictor of insulin resistance in women with polycystic ovary syndrome.

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    Sahin, I; Celik, O; Celik, N; Keskin, L; Dogru, A; Dogru, I; Yürekli, M; Yologlu, S

    2012-06-01

    The aim of the study was to investigate adrenomedullin (ADM) levels and its relation with insulin resistance in women with polycystic ovary syndrome (PCOS). Twenty-nine women with PCOS and 29 age- and body mass index (BMI)- matched control subjects were included in the study. PCOS was defined according to criteria by the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)-sponsored PCOS consensus workshop group. A full clinical and biochemical examination including basal hormones and metabolic profile was performed. Insulin resistance was calculated by using the homeostasis model assessment of insulin resistance index (HOMA-IR). Plasma ADM levels were measured by high performance liquid chromatographic (HPLC) method. Plasma ADM, fasting insulin levels and HOMA-IR were significantly higher in patients with PCOS than the control group. ADM levels were positively correlated with insulin levels and HOMA-IR index. The best cut-off value of ADM levels to identify the presence of insulin resistance (HOMA-IR≥2.7) was 30.44 ng/ml. Calculated odds ratio of insulin resistance by using logistic regression analysis, as predicted by ADM, was 0.15 (95% confidence interval, 0.037-0.628; p=0.009). In multiple regression analysis, ADM level was an independent predictor of HOMA-IR index. Our finding indicated that ADM levels increased in women with PCOS in accordance with HOMA-IR. ADM could be a significant independent determinant of insulin resistance in women with PCOS.

  15. Atypical aging in Down syndrome.

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    Zigman, Warren B

    2013-01-01

    At present, there may be over 210,000 people with Down syndrome (DS) over the age of 55 in the United States (US) who have significant needs for augmented services due to circumstances related to ordinary and/or pathological aging. From 1979 through 2003, the birth prevalence of DS rose from 9.0 to 11.8 (31.1%) per 10,000 live births in 10 representative US regions. This increase, largely due to women conceiving after age 35, portends an ever-growing population of people with DS who may be subject to pathogenic aging. Whereas Trisomy 21 is one of the most widespread genetic causes of intellectual disability (ID), it still is one of the least understood of all genetic ID syndromes. While longevity in people with DS has improved appreciably in as modest a period as 30 years, age-specific risk for mortality still is considerably increased compared both with other people with ID or with the typically developing population. The penetrance of the phenotype is widely distributed, even though a consistent genotype is assumed in 95% of the cases. Some, but not all body systems, exhibit signs of premature or accelerated aging. This may be due to both genetic and epigenetic inheritance. We now know that the long-term outcome for people with DS is not as ominous as once contemplated; a number of people with DS are living into their late 60s and 70s with few if any major signs of pathogenic aging. Alzheimer's disease (AD), a devastating disease that robs a person of their memory, abilities and personality, is particularly common in elder adults with DS, but is not a certainty as originally thought, some 20% to 30% of elder adults with DS might never show any, or at most mild signs of AD. DS has been called a mature well-understood syndrome, not in need of further research or science funding. We are only beginning to understand how epigenetics affects the phenotype and it may be feasible in the future to alter the phenotype through epigenetic interventions. This chapter is

  16. Hyperandrogenism-Insulin Resistance-Acanthosis Nigricans Syndrome

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    A. H. Dédjan

    2015-01-01

    Full Text Available Introduction. Female hyperandrogenism is a frequent motive of consultation. It is revealed by hirsutism, acne or seborrhea, and disorders in menstruation cycle combined or not with virilisation signs. Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. Observation. A 20-year-old girl, having had a five-year-old secondary amenorrhea. The exam revealed a patient, normotensive with a body mass index at 30 kg/m2 and a waist measurement of 120 cm, a severe hirsutism assessed to be 29 according to Ferriman Gallwey scale, virilisation signs of male morphotype, clitoridic hypertrophy and frontal alopecia, and an acanthosis nigricans behind the neck, in the armpits and elbows. The assessment carried out revealed testosteronemia at 1.28 ng/mL, which is more than twice the upper norm of the laboratory. Imaging studies were negative for both ovarian and adrenal masses. The retained diagnosis is HAIR-AN syndrome probably related to ovarian hyperthecosis and she was provided with androcur 50 mg/day and estradiol pills 2 mg/day and under hygiene-dietetic conditions. Conclusion. This case proves that HAIR-AN syndrome could be responsible for severe hyperandrogenism with virilisation signs. It must be retained after discarding the tumoral causes and when there are signs of insulin resistance.

  17. Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

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    Platt, Adrienne M

    2015-07-01

    School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure.

  18. Study of insulin status in metabolic syndrome in correlation with presence of other risk factors

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    Sudhanshu Shekhar

    2016-07-01

    Conclusions: It was observed that metabolic syndrome is associated with elevated serum insulin levels and each component of metabolic syndrome, both biochemical as well as clinical, is associated with hyper-insulinemia and this reflects the presence of insulin resistance in subjects of study. [Int J Res Med Sci 2016; 4(7.000: 2734-2737

  19. Androgen Excess Disorders in Women: The Severe Insulin-Resistant Hyperandrogenic Syndrome, HAIR-AN

    OpenAIRE

    Rager, Kristin M.; Hatim A. Omar

    2006-01-01

    HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans) is a subset of the polycystic ovary syndrome, where the patients demonstrate severe insulin resistance. It is theorized that both genetic and environmental factors, such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily clinical, with laboratory values lending further support. Treatment is aimed at decreasing insulin resistance, regulating ovulation, and decreasing acne, acanthosis nigrican...

  20. Androgen Excess Disorders in Women: The Severe Insulin-Resistant Hyperandrogenic Syndrome, HAIR-AN

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    Kristin M. Rager

    2006-01-01

    Full Text Available HAIR-AN syndrome (hyperandrogenism, insulin resistance, acanthosis nigricans is a subset of the polycystic ovary syndrome, where the patients demonstrate severe insulin resistance. It is theorized that both genetic and environmental factors, such as obesity, give rise to the development of HAIR-AN. Diagnosis is primarily clinical, with laboratory values lending further support. Treatment is aimed at decreasing insulin resistance, regulating ovulation, and decreasing acne, acanthosis nigricans, and hirsutism.

  1. The role of insulin and selected adipocytokines in patients with polycystic ovary syndrome (PCOS) - a literature review.

    Science.gov (United States)

    Ozegowska, Katarzyna E; Pawelczyk, Leszek A

    2015-04-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is manifested by hyperandrogenism, polycystic ovaries on ultrasound, oligomenorrhoea and anovulation. PCOS patients are more vulnerable to metabolic disorders: insulin resistance, obesity endothelium dysfunction, atherosclerosis, and activation of proinflammatory factors. This association shows that PCOS might be an ovarian manifestation of a metabolic syndrome. Insulin resistance is also strongly correlated with reproductive failure. Approximately 100 factors, secreted in adipose tissue, are responsible for its regulation. Adipocytokines have been found to play an important role in regulating insulin sensitivity Abnormal levels of adipokines are detected in patients with insulin resistance. Studies indicate that these factors, and their different activity in PCOS women, may affect changes observed in their metabolism and, especially may participate in the development of insulin resistance. There are several adipokines whose role has been thoroughly investigated and many that we still know very little about, for example apein and visfatin. Counseling PCOS patients about the possibility of developing metabolic syndrome, diabetes mellitus, and cardiovascular diseases should be a standard of care.

  2. THE INFLUENCE OF INSULIN RESISTANCE ON THE FORMATION AND PROGRESSION OF METABOLIC SYNDROME COMPONENTS (THE RESULTS OF A FIVE-YEAR STUDY

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    G. E. Roytberg

    2015-01-01

    Full Text Available The combination of risk factors that make up a metabolic syndrome increases the risk of cardiovascular disease and type 2 diabetes. In the presence of insulin resistance the effects of risk factors combine, thereby increasing the probability of the development of cardiovascular disease and its complications.Aim. To study the effect of insulin resistance on the formation and progression of metabolic syndrome components on the basis of a 5-year follow-up.Material and methods. An outpatient examination of clinically healthy patients aged 20-65 years (n=711; 327 men and 384 women was conducted. The average body mass index did not exceed 34.5 kg/m2. Biochemical blood analysis was performed to assess the state of lipid and carbohydrate metabolism. Insulin resistance was diagnosed using HOMAIR>2.6.Results. It has been detected that patients with insulin resistance have significantly higher incidence of the combination of three or more components of the metabolic syndrome (p<0.01. The incidence of multicomponent syndrome among the examined patients with insulin resistance was 69.7%, which is 1.8 times higher than in patients with initially preserved tissue sensitivity to insulin.Conclusion. The follow-up study of patients with insulin resistance shows that in the absence of correction of metabolic disorders, the development of multicomponent disorders that make up a metabolic syndrome occurs.

  3. THE INFLUENCE OF INSULIN RESISTANCE ON THE FORMATION AND PROGRESSION OF METABOLIC SYNDROME COMPONENTS (THE RESULTS OF A FIVE-YEAR STUDY

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    G. E. Roytberg

    2015-09-01

    Full Text Available The combination of risk factors that make up a metabolic syndrome increases the risk of cardiovascular disease and type 2 diabetes. In the presence of insulin resistance the effects of risk factors combine, thereby increasing the probability of the development of cardiovascular disease and its complications.Aim. To study the effect of insulin resistance on the formation and progression of metabolic syndrome components on the basis of a 5-year follow-up.Material and methods. An outpatient examination of clinically healthy patients aged 20-65 years (n=711; 327 men and 384 women was conducted. The average body mass index did not exceed 34.5 kg/m2. Biochemical blood analysis was performed to assess the state of lipid and carbohydrate metabolism. Insulin resistance was diagnosed using HOMAIR>2.6.Results. It has been detected that patients with insulin resistance have significantly higher incidence of the combination of three or more components of the metabolic syndrome (p<0.01. The incidence of multicomponent syndrome among the examined patients with insulin resistance was 69.7%, which is 1.8 times higher than in patients with initially preserved tissue sensitivity to insulin.Conclusion. The follow-up study of patients with insulin resistance shows that in the absence of correction of metabolic disorders, the development of multicomponent disorders that make up a metabolic syndrome occurs.

  4. Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity.

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    Laron, Zvi

    2002-01-01

    Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

  5. GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

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    Leguisamo Natalia M

    2012-08-01

    Full Text Available Abstract Background Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods Spontaneously hypertensive neonate rats (18/group were treated with monosodium glutamate (MetS during 9 days, and compared with Wistar-Kyoto (C and saline-treated SHR (H. Blood pressure (BP and lipid levels, C-reactive protein (CRP, interleukin 6 (IL-6, TNF-α and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo, 6 (6-mo and 9 (9-mo months of age. Results MetS rats were more insulin resistant (pvs H, but adiponectin was lower in MetS at 9 months (MetS: 32 ± 2, H: 42 ± 2, C: 45 ± 2 pg/mL; p Conclusions MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

  6. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome.

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    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ETAR during insulin resistance, ETAR expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ETAR expression, but not ETBR, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ETAR pathway suppressed insulin-induced AKT

  7. The incidence of metabolic syndrome in obese Czech children: the importance of early detection of insulin resistance using homeostatic indexes HOMA-IR and QUICKI.

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    Pastucha, D; Filipčíková, R; Horáková, D; Radová, L; Marinov, Z; Malinčíková, J; Kocvrlich, M; Horák, S; Bezdičková, M; Dobiáš, M

    2013-01-01

    Common alimentary obesity frequently occurs on a polygenic basis as a typical lifestyle disorder in the developed countries. It is associated with characteristic complex metabolic changes, which are the cornerstones for future metabolic syndrome development. The aims of our study were 1) to determine the incidence of metabolic syndrome (based on the diagnostic criteria defined by the International Diabetes Federation for children and adolescents) in Czech obese children, 2) to evaluate the incidence of insulin resistance according to HOMA-IR and QUICKI homeostatic indexes in obese children with and without metabolic syndrome, and 3) to consider the diagnostic value of these indexes for the early detection of metabolic syndrome in obese children. We therefore performed anthropometric and laboratory examinations to determine the incidence of metabolic syndrome and insulin resistance in the group of 274 children with obesity (128 boys and 146 girls) aged 9-17 years. Metabolic syndrome was found in 102 subjects (37 %). On the other hand, the presence of insulin resistance according to QUICKI 3.16 in 53 % of obese subjects. This HOMA-IR limit was exceeded by 70 % children in the MS(+) group, but only by 43 % children in the MS(-) group (pchildren without metabolic syndrome raises a question whether the existing diagnostic criteria do not falsely exclude some cases of metabolic syndrome. On the basis of our results we suggest to pay a preventive attention also to obese children with insulin resistance even if they do not fulfill the actual diagnostic criteria for metabolic syndrome.

  8. Primary insulin autoimmune syndrome in an Italian woman: a case report

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    Antonio Balestrieri

    2015-05-01

    Full Text Available Insulin autoimmune syndrome (IAS is a rare syndrome characterized by fasting or postprandial hypoglycemia, high levels of anti-insulin antibodies and high concentration of total serum immunoreactive insulin. It is relatively known in Japan, rare in remaining Asia and it is extremely uncommon in Western countries, being characterized by a different race-related incidence and associated with HLADR4 alleles. Usually IAS is related to particular drugs, or to autoimmune, rheumatologic or hematological diseases, while it is very rare as a primary form. Here we described a case of an Italian woman affected by a primary form of Hirata syndrome.

  9. Insulin resistance in adolescents with Down syndrome: a cross-sectional study

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    Beserra Izabel CR

    2005-06-01

    Full Text Available Abstract Background The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR using the HOMA (Homeostasis Model Assessment method, in DS adolescents, describing it according to the sex, body mass index (BMI and pubertal development. Methods 15 adolescents with DS (8 males and 7 females were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN, weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score. Results Five patients were adults (Tanner V or presence of menarche, 9 pubertal (Tanner II – IV and 1 prepubertal (Tanner I. No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively. Conclusion The obese and overweight, female and

  10. Anthropometric measurements for assessing insulin sensitivity on patients with metabolic syndrome, sedentaries and marathoners.

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    Severeyn, Erika; Wong, Sara; Herrera, Hector; Altuve, Miguel

    2015-08-01

    The diagnosis of low insulin sensitivity is commonly done through the HOMA-IR index, in which fasting insulin and glucose blood levels are evaluated. Insulin and blood glucose levels are used for insulin sensitivity assessment by surrogate methods (HOMA-IR, Matsuda, etc), but anthropometric measurements like body weight, height and waist circumference are not considered, even if these variables also are related to low insulin sensitivity and metabolic syndrome. In this study we evaluate the impact of anthropometric measurements on the HOMA-IR, Matsuda and Caumo indexes to estimate insulin sensitivity. Specifically, we compare insulin sensitivity indexes with and without the anthropometric measurements in their equations on three different groups: patients with metabolic syndrome, sedentaries and marathoners. Results show relationships between anthropometric variables and insulin sensitivity indexes. On the other hand, subjects are mapped differently for insulin sensitivity assessment when anthropometric variables are taken into account. In addition, subjects diagnosed with normal insulin sensitivity could be considered as having low insulin sensitivity when anthropometric variables are considered.

  11. Type B insulin resistance syndrome induced by systemic lupus erythematosus and successfully treated with intravenous immunoglobulin: case report and systematic review.

    Science.gov (United States)

    Zhang, Sigong; Wang, Guochun; Wang, Jinping

    2013-02-01

    Type B insulin resistance syndrome is characterized by the formation of autoantibodies against insulin receptors, which can cause severe hyperglycemia and insulin resistance. Systemic lupus erythematosus is the most common underlying diseases of the syndrome. This report details our study of a case involving a Chinese female with type B insulin resistance syndrome as well as systemic lupus erythematosus who completely recovered after undergoing immunosuppressive therapy, specifically pulse therapy utilizing intravenous immunoglobulin. We also conducted search in MEDLINE and Chinese BioMedicine database to identify relevant literatures published in the past 46 years. From our searches, six case reports in Chinese, 15 case reports, and a 28-year perspective article in English met our criteria; a total of 67 cases were included in our report. The mean age of subjects at presentation for groups A, B, and C were 42.95, 44.10, and 41.68 years, respectively, yielding no significant difference between these groups. African Americans were the most susceptible group to type B insulin resistance syndrome, followed by Asians representing 20.90 % of all cases. Comparisons between the three main racial groups surveyed indicated that the mean age of subjects at presentation were very contiguous for African Americans and Asians, and mean age of white people was remarkably higher than either of the first two groups. The syndrome appeared most common among Asian males, and white males were relatively less likely to suffer from type B insulin resistance syndrome. Hypoglycemia was most commonly observed in white people than in other racial groups. Hypoalbuminemia, elevated serum immunoglobulin G, and elevated sedimentation rates were more common in African Americans; Asian cases were more likely to show low serum C3 or C4 and nephritis. Two cases received intravenous immunoglobulin therapy, which has a remarkably rapid effect on insulin resistance.

  12. Accelerated epigenetic aging in Down syndrome

    OpenAIRE

    Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

    2015-01-01

    Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P ...

  13. Ozone (O3): A Potential Contributor to Metabolic Syndrome through Altered Insulin Signaling

    Science.gov (United States)

    Air pollutants have been associated with diabetes and metabolic syndrome, but the mechanisms remain to be elucidated. We hypothesized that acute O3 exposure will produce metabolic impairments through endoplasmic reticular stress (ER) stress and altered insulin signaling in liver,...

  14. Transfer of Intestinal Microbiota From Lean Donors Increases Insulin Sensitivity in Individuals With Metabolic Syndrome

    NARCIS (Netherlands)

    Vrieze, Anne; Van Nood, Els; Holleman, Frits; Salojarvi, Jarkko; Kootte, Ruud S.; Bartelsman, Joep F. W. M.; Dallinga-Thie, Geesje M.; Ackermans, Mariette T.; Serlie, Mireille J.; Oozeer, Raish; Derrien, Muriel; Druesne, Anne; van Hylckama Vlieg, Johan E.T.; Bloks, Vincent W.; Groen, Albert K.; Heilig, Hans G. H. J.; Zoetendal, Erwin G.; Stroes, Erik S.; de Vos, Willem M.; Hoekstra, Joost B. L.; Nieuwdorp, Max

    2012-01-01

    Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned rando

  15. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Directory of Open Access Journals (Sweden)

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  16. Relationship of hypovitaminosis d and insulin resistance in patients with coronary heart disease and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    V. F. Orlovsky

    2013-08-01

    Full Text Available BACKGROUND: Insulin resistance (IR - is one of the predictors of cardiovascular disease and progression of atherosclerosis, regardless of major classical risk factors. IR has become a global epidemic. Experimental data indicate that low concentration of vitamin D associated with IR, diabetes mellitus type 2, by reducing the sensitivity of peripheral tissues to insulin and dysfunction of β-pancreatic cells. Randomized studies showed that vitamin D supplements have a preventive role in the development of type 2 diabetes mellitus (DM. The present study aims to examine the association between serum vitamin D concentrations and indicators of carbohydrate metabolism, indexes of insulin resistance and insulin sensitivity in the patients with coronary artery disease. METHODS: This study included 135 patients with CHD stable angina pectoris class II – III. The mean age was 64,7±0,97 years, 40% were women (n = 54. Patients were divided into two groups: I – with isolated CHD (70 patients and II - CHD combined with MS (65 patients. MS was diagnosed according to the criteria of the International Diabetes Federation (IDF, 2005. The study did not include patients who received vitamin D2, D3 and multivitamins containing these vitamins for last 6 months, patients with malabsorption fat syndrome, acute and chronic liver disease, chronic renal failure, nephrotic syndrome, urolithiasis, and primary hyperparathyroidism. Also excluded from the study were patients with DM type 1 and type 2 taking glucose-lowering drugs. Serum 25(OHD and insulin were measured by enzyme immunoassay (25-OH Vitamin D Immunodiagnostics Systems Limited (UK; DRG (USA. RESULT: Vitamin D deficiency or insufficiency was present in 91,9 % of the tested patients. Among subnormal values prevailed insufficiency in 51,9 % (70 pers., deficit diagnosed in 40.0% of patients (54 pers.. Established that patients with CHD associated with MS have a significantly more pronounced hypovitaminosis D

  17. Effects of sex steroids on components of the insulin resistance syndrome in transsexual subjects

    NARCIS (Netherlands)

    Elbers, J.M.H.; Giltay, E.J.; Teerlink, T.; Scheffer, P.G.; Asscheman, H.; Seidell, J.C.; Gooren, L.J.G.

    2003-01-01

    objective Sex differences are found in most components of the insulin resistance syndrome and the associated cardiovascular risk profile. These differences are attributed to sex-specific sex steroid profiles, but the effects of sex steroids on the individual components of the insulin resistance synd

  18. Insulin action in women with polycystic ovary syndrome and its relation to gestational diabetes

    NARCIS (Netherlands)

    De Wilde, Marlieke A.; Goverde, Angelique J.; Veltman-Verhulst, Susanne M.; Eijkemans, Marinus J C; Franx, Arie; Fauser, Bart C J M; Koster, Maria P H

    2015-01-01

    STUDY QUESTION: How does insulin action change during pregnancy in women with polycystic ovary syndrome (PCOS) who develop gestational diabetes (GDM) compared with women with PCOS who do not? SUMMARY ANSWER: Women with PCOS who develop GDM already show disturbed insulin action early in pregnancy. WH

  19. Age- and sex-related reference values for serum insulin concentration and its biological determinants in a French healthy population. The STANISLAS cohort.

    Science.gov (United States)

    François, Aurélie; Maumus, Sandy; Vincent-Viry, Monique; Guéguen, René; Siest, Gérard; Visvikis, Sophie

    2004-01-01

    Insulin is involved in coronary heart disease through diabetes and metabolic syndrome. A great deal is known about insulin and its correlates, as well as factors related to changes in insulin. However, few studies consider the broad variety of correlates simultaneously. Therefore, the aims of the present study were to characterize the main factors of biological variation affecting serum insulin concentration and to establish reference limits of insulinemia in a presumably healthy French population. Insulin was measured using a microparticular enzymatic immunoassay. A total of 646 subjects aged 11-58 years from the STANISLAS cohort and divided into four groups of 162 males, 157 females, 163 boys and 164 girls, were included in the statistical analyses. In the whole population, serum insulin concentration varied from 0.80 to 54.60 microU/ml. Significant factors affecting insulin were age, gender, body mass index and glucose, in addition to alanine aminotransferase and high-density lipoprotein cholesterol in men, triglycerides and oral contraceptive use in women, and alkaline phosphatase in girls. In summary, we presented biological correlates of insulin in both healthy French male and female adults and children/adolescents and determined reference limits for insulin for each group. These results will contribute to a better interpretation of insulin data in further studies and laboratory investigations.

  20. Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity

    Directory of Open Access Journals (Sweden)

    Rodriguez Susana

    2008-08-01

    Full Text Available Abstract Background Obesity is a one of the most common nutritional disorder worldwide, clearly associated with the metabolic syndrome, condition with implications for the development of many chronic diseases. In the poorest countries of Latin America, malnourishment is still the most prevalent nutritional problem, but obesity is emerging in alarming rates over the last 10 years without a predictable association with metabolic syndrome. The objective of our study was to determine the association between insulin-resistance and components of the metabolic syndrome in a group of Bolivian obese children and adolescents. The second objective was determining the relation of acanthosis nigricans and insulin-resistance. Methods We studied 61 obese children and adolescents aged between 5 and 18 years old. All children underwent an oral glucose tolerance test and fasting blood sample was also obtained to measure insulin, HDL, LDL and triglycerides serum level. The diagnosis of metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III criteria adapted for children. Results Metabolic syndrome was found in 36% of the children, with a higher rate among males (40% than females (32.2% (p = 0.599. The prevalence of each of the components was 8.2% in impaired glucose tolerance, 42.6% for high triglyceride level, 55.7% for low levels of high-density lipoprotein cholesterol, and 24.5% for high blood pressure. Insulin resistance (HOMA-IR > 3.5 was found in 39.4% of the children, with a higher rate in males (50% than females (29%. A strong correlation was found between insulin resistance and high blood pressure (p = 0.0148 and high triglycerides (p = 0.002. No statistical significance was found between the presence of acanthosis nigricans and insulin resistance. Conclusion Metabolic syndrome has a prevalence of 36% in children and adolescent population in the study. Insulin resistance was very common among

  1. Ageing and Brugada syndrome: considerations and recommendations

    Institute of Scientific and Technical Information of China (English)

    Pieter G. Postema; Hanno L Tan; Arthur AM Wilde

    2013-01-01

    Brugada syndrome is an inherited disease associated with an increased risk of lethal ventricular arrhythmias. Such arrhythmias stem from innate disruptions in cardiac electrophysiology. Typically, such arrhythmias occur in the third or fourth decade of life. However, Brugada syndrome may also affect geriatric patients. In this paper, we focus on the ageing patient with Brugada syndrome, and specifically, on the interaction between Brugada syndrome and the more usually acquired clinical problems that may occur with increasing age, such as the use of cardiovascular and non-cardiovascular drugs, or the need for surgery. Such common conditions may also disrupt cardiac electrophysiology, thereby conferring added risk for Brugada syndrome patients. We present some considerations and recommendations that may serve as guidance to address these complexities.

  2. Deletion of insulin-degrading enzyme elicits antipodal, age-dependent effects on glucose and insulin tolerance.

    Directory of Open Access Journals (Sweden)

    Samer O Abdul-Hay

    Full Text Available BACKGROUND: Insulin-degrading enzyme (IDE is widely recognized as the principal protease responsible for the clearance and inactivation of insulin, but its role in glycemic control in vivo is poorly understood. We present here the first longitudinal characterization, to our knowledge, of glucose regulation in mice with pancellular deletion of the IDE gene (IDE-KO mice. METHODOLOGY: IDE-KO mice and wild-type (WT littermates were characterized at 2, 4, and 6 months of age in terms of body weight, basal glucose and insulin levels, and insulin and glucose tolerance. Consistent with a functional role for IDE in insulin clearance, fasting serum insulin levels in IDE-KO mice were found to be ∼3-fold higher than those in wild-type (WT controls at all ages examined. In agreement with previous observations, 6-mo-old IDE-KO mice exhibited a severe diabetic phenotype characterized by increased body weight and pronounced glucose and insulin intolerance. In marked contrast, 2-mo-old IDE-KO mice exhibited multiple signs of improved glycemic control, including lower fasting glucose levels, lower body mass, and modestly enhanced insulin and glucose tolerance relative to WT controls. Biochemically, the emergence of the diabetic phenotype in IDE-KO mice correlated with age-dependent reductions in insulin receptor (IR levels in muscle, adipose, and liver tissue. Primary adipocytes harvested from 6-mo-old IDE-KO mice also showed functional impairments in insulin-stimulated glucose uptake. CONCLUSIONS: Our results indicate that the diabetic phenotype in IDE-KO mice is not a primary consequence of IDE deficiency, but is instead an emergent compensatory response to chronic hyperinsulinemia resulting from complete deletion of IDE in all tissues throughout life. Significantly, our findings provide new evidence to support the idea that partial and/or transient inhibition of IDE may constitute a valid approach to the treatment of diabetes.

  3. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects

    DEFF Research Database (Denmark)

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian;

    2013-01-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intrav......It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during...

  4. Novel adiponectin-resistin (AR and insulin resistance (IRAR indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

    Directory of Open Access Journals (Sweden)

    Muniandy Sekaran

    2011-01-01

    Full Text Available Abstract Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM, metabolic syndrome (MS and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0-log10(A0. The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0+log10(I0G0log10(R0/A0. The normal reference range of the IRAR index for insulin sensitive individuals was

  5. Altered expression of genes involved in mitochondrial oxidative phosphorylation and insulin signaling in skeletal muscle of obese women with polycystic ovary syndrome (PCOS)

    DEFF Research Database (Denmark)

    Skov, Vibe

    be of similar importance for insulin resistance in the polycystic ovary syndrome (PCOS).   Materials and methods: Using the HG-U133 Plus 2.0 expression array from Affymetrix, we analyzed gene expression in skeletal muscle from obese women with PCOS (n=16) and age- and body mass index-matched control women (n=13......-stimulated glucose disposal - caused by reduced glucose oxidation and storage - as well as impaired suppression of lipid oxidation (all P... in the insulin signaling pathway may contribute to insulin resistance in PCOS. These abnormalities may play an important role for the increased risk of type 2 diabetes observed in these women.  ...

  6. [Insulin resistance and hyperinsulinemia--risk factors of the metabolic syndrome in the pubertal population].

    Science.gov (United States)

    Otto Buczkowska, Ewa

    2005-01-01

    Pubertal insulin resistance has been well documented, the fall in insulin sensitivity (Sl) during puberty is associated with a compensatory increase in insulin secretion. Observation of pubertal insulin resistance showed that insulin-stimulated glucose metabolism was approximately 30% lower in a sample of children at Tanner stages II-IV compared with children at Tanner stage I or adults. Although the phenomenon of pubertal insulin resistance is well documented, the mechanism has not been clearly determined. Pubertal insulin resistance occurs during a time of profound changes in body composition and hormone levels. Resistance of the body to the actions of insulin results in increased production of this hormone by the pancreas and ensuing hyperinsulinemia. Obesity beginning in childhood often precedes the hyperinsulinemic state. Other components of the insulin resistance syndrome are also present in children and adolescents. Conditions of insulin resistance, hyperinsulinemia, dyslipidemia, hypertension and obesity, especially in constellation, are potent risk factors of coronary atherosclerosis among adolescents and young adults. Early conservative intervention with diet, exercise, and behavioral therapy may prevent the complications of insulin resistance.

  7. Cinnamon: potential role in the prevention of insulin resistance, metabolic syndrome, and type 2 diabetes

    Science.gov (United States)

    The metabolic syndrome is associated with insulin resistance, elevated glucose and lipids, inflammation, decreased antioxidant activity, increased weight gain, and increased glycation of proteins. Cinnamon has been shown to improve aspects of metabolic syndrome in cells cultured in vitro, and in an...

  8. Associations of Prenatal Growth with Metabolic Syndrome, Insulin Resistance, and Nutritional Status in Chilean Children

    Science.gov (United States)

    Mardones, Francisco; Arnaiz, Pilar; Pacheco, Paz; Dominguez, Angelica; Villarroel, Luis; Eriksson, Johan G.; Barja, Salesa; Farías, Marcelo; Castillo, Oscar

    2014-01-01

    Introduction. The association of prenatal growth with nutritional status, metabolic syndrome (MS), and insulin resistance (IR) was studied in school-age children. Methods. A retrospective cohort study was designed linking present data of children with perinatal records. 3325 subjects were enrolled. Anthropometry, blood pressure (BP), and pubertal status were assessed. Blood lipids, glucose, and insulin were measured. Linear associations were assessed using the Cochran-Armitage test. Odds ratios and nonlinear associations were computed. Results. 3290 children (52% females, mean age of 11.4 ± 1 years) were analyzed. Prevalence of obesity, stunting, MS, and IR was 16.0%, 3.6%, 7.3%, and 25.5%, respectively. The strongest positive association was between birth weight (BW) and obesity (OR 2.97 (95% CI 2.01–4.40) at BW ≥ 4,000 g compared to BW 2,500–2,999). The strongest inverse association was between birth length (BL) and stunting (OR 8.70 (95% CI 3.66–20.67) at BL < 48 cm compared to BL 52-53 cm). A U-shaped association between BL and BP ≥ 90th percentile was observed. Significant ORs were also found for MS and IR. Adjustments for present fat mass increased or maintained the most prenatal growth influences. Conclusions. Prenatal growth influences MS, IR, and nutritional status. Prenatal growth was more important than present body composition in determining these outcomes. PMID:25025054

  9. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  10. Accelerated epigenetic aging in Down syndrome.

    Science.gov (United States)

    Horvath, Steve; Garagnani, Paolo; Bacalini, Maria Giulia; Pirazzini, Chiara; Salvioli, Stefano; Gentilini, Davide; Di Blasio, Anna Maria; Giuliani, Cristina; Tung, Spencer; Vinters, Harry V; Franceschi, Claudio

    2015-06-01

    Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10(-14)).

  11. Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

    Science.gov (United States)

    Forbes, Josephine M; Sourris, Karly C; de Courten, Maximilian P J; Dougherty, Sonia L; Chand, Vibhasha; Lyons, Jasmine G; Bertovic, David; Coughlan, Melinda T; Schlaich, Markus P; Soldatos, Georgia; Cooper, Mark E; Straznicky, Nora E; Kingwell, Bronwyn A; de Courten, Barbora

    2014-02-01

    It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

  12. Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms.

    Science.gov (United States)

    Guo, Shaodong

    2014-02-01

    Insulin resistance is a major underlying mechanism responsible for the 'metabolic syndrome', which is also known as insulin resistance syndrome. The incidence of the metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. The metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies have demonstrated that insulin and its signaling cascade normally control cell growth, metabolism, and survival through the activation of MAPKs and activation of phosphatidylinositide-3-kinase (PI3K), in which the activation of PI3K associated with insulin receptor substrate 1 (IRS1) and IRS2 and subsequent Akt→Foxo1 phosphorylation cascade has a central role in the control of nutrient homeostasis and organ survival. The inactivation of Akt and activation of Foxo1, through the suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and overnutrition, may act as the underlying mechanisms for the metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will probably provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the features of the metabolic syndrome. Emphasis is placed on the role of IRS1, IRS2, and associated signaling pathways that are coupled to Akt and the forkhead/winged helix transcription factor Foxo1.

  13. A Cross-Sectional Study of the Phenotypes of Obesity and Insulin Resistance in Adults with Down Syndrome

    Directory of Open Access Journals (Sweden)

    Diego Real de Asua

    2014-12-01

    Full Text Available BackgroundDespite the confluence of multiple cardiovascular risk factors, subclinical atherosclerotic damage and cardiovascular events remain extremely rare in adults with Down syndrome (DS. We aim to determine the prevalence of obesity and metabolic disorders in an adult cohort with DS and to compare our findings with adults without DS.MethodsCross-sectional study of 51 consecutively selected adults with DS living in the community and 51 healthy controls in an outpatient clinic of a tertiary care hospital in Madrid, Spain. Epidemiological data (age and gender, anthropometric data (body mass index and waist-to-height ratio, coexisting clinical conditions, and laboratory data (fasting glucose, insulin, glycated hemoglobin, creatinine, thyroid hormones, vitamins, and lipid profile were measured and compared between the groups.ResultsAdults with DS were significantly younger and more often men with a higher prevalence of overweight and obesity than controls. Their waist-to-height ratio was higher, and they more frequently had abdominal obesity. The results of an analysis adjusted for age and gender revealed no differences in fasting insulin levels, homeostatic model assessment indexes, or lipid profile between adults with DS and controls.ConclusionAdults with DS presented a high prevalence of overweight and obesity. However, we found no differences in lipid profile, prevalence of insulin resistance, or metabolic syndrome between adults with DS and controls.

  14. An isocaloric low glycemic index diet improves insulin sensitivity in women with polycystic ovary syndrome.

    Science.gov (United States)

    Barr, Suzanne; Reeves, Sue; Sharp, Kay; Jeanes, Yvonne M

    2013-11-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5% to 10% of women worldwide. Approximately half of women with PCOS are lean, yet may still present with central obesity and metabolic disturbances. Low-glycemic index (GI) dietary intervention studies have demonstrated improvements in insulin sensitivity in insulin-resistant populations; however, there is little evidence of this effect in women with PCOS. This research aimed to determine the efficacy of an isocaloric low-GI dietary intervention on insulin sensitivity, independent of weight change, in women with PCOS. A nonrandomized 12-week low-GI dietary intervention, preceded by a 12-week habitual diet control phase and proceeded by a 12-week follow-up phase was conducted. Dietary intake, body composition, and metabolic risk markers were determined at baseline, after completion of the habitual diet control phase, and after the low-GI dietary intervention. Twenty-six participants were recruited at baseline, 22 commenced and 21 participants completed the low-GI dietary intervention phase. The primary outcome was change in insulin sensitivity. Secondary outcomes included assessment of changes to lipids, body composition, and estimated macronutrient intake. Repeated measures analysis of variance with Bonferroni correction were used to detect changes to outcomes across study timepoints. Twenty-one women with PCOS with mean (± standard deviation) age of 32.1±6.7 years completed the 12-week low-GI dietary intervention. As expected, no significant changes occurred during the 12-week habitual diet control phase. However, during the dietary intervention phase, dietary GI decreased from 54.5±3.5 to 48.6±5.1 (P<0.001) with a concurrent small reduction in saturated fat intake (12.4%±3% to 11.7%±3% contribution from energy, P=0.03), despite no specific recommendations to modify fat intake. Measures of insulin sensitivity and nonesterified fatty acid improved after intervention (P=0.03 and P=0

  15. The insulin-resistant phenotype of polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Svendsen, Pernille Fog; Madsbad, Sten; Nilas, Lisbeth

    2009-01-01

    insulin resistance (IR) index. RESULT(S): Multiple regression analysis showed that body mass index (BMI) and hirsutism were independent predictors of IR evaluated by insulin sensitivity index, whereas BMI, total T, and hirsutism were independent predictors of IR evaluated by the homeostatic model...

  16. Aging in Rare Intellectual Disability Syndromes

    Science.gov (United States)

    Dykens, Elisabeth M.

    2013-01-01

    This review highlights several methodological challenges involved in research on aging, health, and mortality in adults with rare intellectual disability syndromes. Few studies have been performed in this area, with research obstacles that include: the ascertainment of older adults with genetic versus clinical diagnoses; likelihood that adults…

  17. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    OpenAIRE

    Shou-Kui Xiang; Fei Hua; Ying Tang; Xiao-Hong Jiang; Qi Zhuang; Feng-Juan Qian

    2012-01-01

    Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS). Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), total testosterone (T), fasting glucose (FBG), fasting insulin (FINS), serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lip...

  18. Chemerin as a marker of body fat and insulin resistance in women with polycystic ovary syndrome.

    Science.gov (United States)

    Kort, Daniel H; Kostolias, Alessandra; Sullivan, Chantae; Lobo, Roger A

    2015-02-01

    Adipocytokines may alter normal metabolic function and play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). We prospectively evaluated a cohort of obese and non-obese women with PCOS and non-PCOS controls for both novel (chemerin and omentin-1) and established (leptin and adiponectin) adipokines. Compared with age-matched controls, non-obese women with PCOS had decreased serum omentin-1 (191.1 ng/ml versus 269.7 ng/ml, p = 0.0001), while serum chemerin was not significantly altered in women with PCOS (53.95 ng/ml versus 48.61 ng/ml, p = 0.11). The findings were similar in the entire group of women with PCOS. However, in women with PCOS, chemerin correlated with leptin (r = 0.508, p = 0.004), adiponectin (r = -0.36, p = 0.014), and the leptin/adiponectin (L/A) ratio (r = 0.605, p women with PCOS, chemerin correlated with BMI (r = 0.317, p = 0.034), abdominal subcutaneous fat (r = 0.451, p = 0.0019), and insulin resistance (HOMA-IR, r = 0.428, p = 0.0034), while omentin-1 did not correlate with any parameter. These data suggest that chemerin although not significantly elevated in women with PCOS correlates with adiposity and insulin resistance, and it is the single best adipokine measured in this regard. Chemerin, through its inflammatory role as a chemo-attractant in adipose tissue, may be an important determinant of insulin resistance in PCOS.

  19. Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice.

    Science.gov (United States)

    Baron, Stephanie; Bedarida, Tatiana; Cottart, Charles-Henry; Vibert, Francoise; Vessieres, Emilie; Ayer, Audrey; Henrion, Daniel; Hommeril, Baptiste; Paul, Jean-Louis; Renault, Gilles; Saubamea, Bruno; Beaudeux, Jean-Louis; Procaccio, Vincent; Nivet-Antoine, Valerie

    2014-03-01

    Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

  20. Cinnamon improves insulin sensitivity, prevents mesenteric fat accumulation, and increases glycogen synthesis in an animal model of the metabolic syndrome

    Science.gov (United States)

    In Western countries, over consumption of fat and/or refined carbohydrates are leading causes of insulin resistance, obesity, and the metabolic syndrome. Some nutritional factors, including many polyphenols, may be beneficial in counteracting insulin resistance associated with the metabolic syndrom...

  1. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R;

    1995-01-01

    Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...

  2. The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance.

    Science.gov (United States)

    Kendall, David M; Harmel, Anne Peters

    2002-12-01

    The most common and clinically important complication in adults with diabetes is cardiovascular disease (CVD), which includes coronary heart disease, peripheral vascular disease, and stroke. Both type 2 diabetes and the insulin resistance syndrome are associated with a marked increase in the risk for CVD. The metabolic syndrome and the closely related insulin resistance syndrome have recently been recognized as important disorders, each being associated with an increase in CVD risk even in the absence of glucose intolerance. Given the significant public health burden of CVD, risk reduction has emerged as a significant clinical challenge for most practitioners. Diabetes and the insulin resistance syndrome are closely related disorders, with insulin resistance being more than a key pathogenic defect in type 2 diabetes. Even in the absence of glucose intolerance, these 2 disorders are both associated with a number of distinct pathologic findings, including hypertension, atherogenic dyslipidemia, a prothrombotic environment, and significant vascular and hemodynamic abnormalities that result from endothelial cell dysfunction. Insulin resistance is now recognized to be closely associated with the development of each of these risk factors. This article uses a case-based approach to discuss the unique features of insulin resistance and type 2 diabetes considered to be key contributors to CVD risk. A systematic approach to both evaluation and management is proposed, with priority given to therapies of demonstrated clinical benefit. Because of its critical and central role in the development of many CVD risk factors, targeted treatment of insulin resistance will also be discussed as such therapy may prove to be a critical component of care in years to come.

  3. Insulin in Acute Coronary Syndrome: a Narrative Review with Contemporary Perspectives.

    Science.gov (United States)

    Nam, Michael C Y; Byrne, Christopher D; Kaski, Juan Carlos; Greaves, Kim

    2016-10-01

    The role of insulin in the treatment of acute coronary syndrome (ACS) has been widely studied over the past 100 years. The current indication for its use in this context is the treatment of hyperglycemia, irrespective of diabetes, which is associated with adverse outcome. Initial theories proposed that glucose was beneficial in the context of myocardial ischemia and insulin was required to enable glucose cell uptake. However, studies testing this hypothesis with routine insulin administration during ACS have produced disappointing results and research interest has therefore declined. We propose that the less well known but important vasodilator effect of insulin has been overlooked by some of these studies and warrants further consideration. Previous reports have shown that hyperinsulinemic euglycaemia improves myocardial blood flow reserve. With this in mind, this review considers the role of insulin in the context of ACS from the perspective of a vasodilator rather than a metabolic modulator. We discuss the importance of time to treatment, dosage of insulin administered, problems with hypoglycaemia and insulin resistance, and how they may have affected the outcomes of the major trials. Finally, we propose new study designs that allow determination of the optimal vasodilator conditions for the use of insulin as adjunctive pharmacotherapy during myocardial ischaemia.

  4. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

    Science.gov (United States)

    Thauvin-Robinet, Christel; Auclair, Martine; Duplomb, Laurence; Caron-Debarle, Martine; Avila, Magali; St-Onge, Judith; Le Merrer, Martine; Le Luyer, Bernard; Héron, Delphine; Mathieu-Dramard, Michèle; Bitoun, Pierre; Petit, Jean-Michel; Odent, Sylvie; Amiel, Jeanne; Picot, Damien; Carmignac, Virginie; Thevenon, Julien; Callier, Patrick; Laville, Martine; Reznik, Yves; Fagour, Cédric; Nunes, Marie-Laure; Capeau, Jacqueline; Lascols, Olivier; Huet, Frédéric; Faivre, Laurence; Vigouroux, Corinne; Rivière, Jean-Baptiste

    2013-01-01

    Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. PMID:23810378

  5. Associations of Prenatal Growth with Metabolic Syndrome, Insulin Resistance, and Nutritional Status in Chilean Children

    Directory of Open Access Journals (Sweden)

    Francisco Mardones

    2014-01-01

    Full Text Available Introduction. The association of prenatal growth with nutritional status, metabolic syndrome (MS, and insulin resistance (IR was studied in school-age children. Methods. A retrospective cohort study was designed linking present data of children with perinatal records. 3325 subjects were enrolled. Anthropometry, blood pressure (BP, and pubertal status were assessed. Blood lipids, glucose, and insulin were measured. Linear associations were assessed using the Cochran-Armitage test. Odds ratios and nonlinear associations were computed. Results. 3290 children (52% females, mean age of 11.4 ± 1 years were analyzed. Prevalence of obesity, stunting, MS, and IR was 16.0%, 3.6%, 7.3%, and 25.5%, respectively. The strongest positive association was between birth weight (BW and obesity (OR 2.97 (95% CI 2.01–4.40 at BW ≥ 4,000 g compared to BW 2,500–2,999. The strongest inverse association was between birth length (BL and stunting (OR 8.70 (95% CI 3.66–20.67 at BL < 48 cm compared to BL 52-53 cm. A U-shaped association between BL and BP ≥ 90th percentile was observed. Significant ORs were also found for MS and IR. Adjustments for present fat mass increased or maintained the most prenatal growth influences. Conclusions. Prenatal growth influences MS, IR, and nutritional status. Prenatal growth was more important than present body composition in determining these outcomes.

  6. Serum inhibin A concentration in women with polycystic ovarian syndrome and the correlation to ethnicity, androgens and insulin resistance.

    Science.gov (United States)

    Segal, Shimon; Elmadjian, Malvina; Takeshige, Takeko; Karp, Steven; Mercado, Ray; Rivnay, Benjamin

    2010-05-01

    A prospective case-series in an academic hospital clinic was performed to determine whether there is a relationship between polycystic ovarian syndrome (PCOS) and ethnicity. Also, serum inhibin A concentrations were compared between PCOS and normal-ovulatory women. The possibility of a correlation between inhibin A, androgens and insulin resistance in PCOS women was evaluated. Serum inhibin A concentrations were measured in anovulatory PCOS patients (n=32) and in control women of reproductive age (n=16). Statistical analysis was performed using the Mann-Whitney U-test. Serum concentrations of inhibin A, follicle-stimulating hormone, LH, prolactin, thyroid-stimulating hormone, fasting glucose, insulin, testosterone, 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulphate (DHEAS) were measured. Inhibin A concentrations were significantly lower (4.5+/-4.8 pg/ml) when compared with the control group (13.2+/-14.4 pg/ml; P=0.003) and were not significantly different between Hispanic and Caucasian women diagnosed with PCOS. There was no correlation between inhibin A concentrations and insulin, testosterone, free testosterone, 17-OHP, or DHEAS concentrations. In PCOS women, inhibin A concentrations are similar between Hispanic and Caucasian women; however, women with PCOS, regardless of ethnicity, have a lower inhibin A concentration compared with normal-ovulatory women. No correlation was observed between inhibin A androgens and insulin resistance in women diagnosed with PCOS.

  7. Insulin resistance syndrome and left ventricular mass in an elderly population (The Rotterdam Study)

    NARCIS (Netherlands)

    Rheeder, P; Stolk, RP; Mosterd, A; Pols, HAP; Hofman, A; Grobbee, DE

    1999-01-01

    In a study of elderly men and women, age, body mass index, and systolic blood pressure (and in men, also glucose) were significant predictors of left ventricular mass. Postload insulin was not independently associated with left ventricular mass.

  8. Involvement of the pancreatic renin-angiotensin system in insulin resistance and the metabolic syndrome.

    Science.gov (United States)

    Leung, Po Sing; de Gasparo, Marc

    2006-01-01

    The cardiometabolic syndrome consists of several major components: hypertension, hyperinsulinemia, hyperlipidemia, and hyperglycemia. Central to this syndrome are insulin resistance and generation of reactive oxygen species; these features are particularly prominent in patients with type 2 diabetes mellitus. In this context, large clinical trials have shown that blockade of the renin-angiotensin system (RAS) is protective against type 2 diabetes. In spite of these solid clinical data, the mechanistic pathways by which RAS blockade achieves these protective effects have yet to be resolved. A recently identified local pancreatic islet RAS has, however, been implicated in this regard. Furthermore, RAS blockade was recently shown to enhance islet blood flow, oxygen tension, and insulin biosynthesis, thus improving beta-cell function and glucose tolerance. Meanwhile, RAS activation may also influence islet cell inflammatory responses, apoptosis, fibrosis, and superoxide anion production. This RAS-associated oxidative stress can induce islet cell dysfunction in the pancreas and insulin resistance in peripheral tissues.

  9. Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome

    NARCIS (Netherlands)

    H.J. Thierry van Dessel; P.D.K. Lee (Philip); G. Faessen; B.C.J.M. Fauser (Bart); L.C. Giudice

    1999-01-01

    textabstractPolycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We i

  10. The potential role of adenosine in the pathophysiology of the insulin resistance syndrome

    NARCIS (Netherlands)

    Bakker, SJL; Gans, ROB; ter Maaten, JC; Teerlink, T; Westerhoff, HV; Heine, RJ

    2001-01-01

    An increased intracellular availability of the co-enzyme A esters of long-chain fatty acids is thought to underlie many aspects of the insulin resistance syndrome. However, the cause of clustering of a hyperdynamic circulation, sympathetic activation. hypertension, hyperuricaemia, and a raised haema

  11. Age and body mass related changes of cardiovascular risk factors in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Macut Đuro P.

    2002-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is considered a metabolic disorder closely related to obesity, insulin resistance (IR, hyperinsulinemia and unfavorable lipid profile, all increasing the risk for the occurrence of cardiovascular diseases. The aim of this study was to assess age and body mass index (BMI related changes of cardiovascular risk factors in 90 women with PCOS. The cut-off age point was 30 years and for BMI 27.8 kg/m2. In all patients systolic and diastolic blood pressure (BP, metabolic parameters comprising values of glucose and insulin during oral glucose tolerance test (OGTT, and basal lipid values were determined. Significant increase in blood pressure (BP indices, basal insulin values and insulin resistance (IR assessed by HOMA model were observed with aging and the increase of BMI, while the parameters of glucose metabolism, total cholesterol and triglycerides were significantly elevated only with aging. However, the correlation between the indices of arterial blood pressure, and lipid and glucose metabolism parameters occurred only in patients over 30 years of age, pointing to the causative relation and the consequent deterioration of IR and lipid profile with aging, influencing cardiovascular function in women with PCOS.

  12. Study on the Relationship between Insulin-Resistance and Syndrome Differentiation Typing in Hypertension Patients

    Institute of Scientific and Technical Information of China (English)

    刘惠文; 张铁忠; 李光伟; 姜亚云

    2001-01-01

    Objective:To find the relationship between insulin-resistance and Syndrome Differentiation type (SDT) in hypertensive patients.Methods: Two hundred and nine patients of early stage hypertention with no complications of heart, brain or kidney were selected and classified into 4 types according to SDT, the Liver-Fire exuberant type (A), the Phlegm-Dampness abundant type (B), the Yin-Deficiency and Yang-Excess type (C) and the Deficiency of both Yin and Yang type (D). Their insulin sensitivity was examined and compared with that of 40 healthy subjects.Results:(1) Compared with the healthy subjects, all hypertensive patients had apparent insulin resistance (P<0.05).If the insulin sensitivity of healthy subjects was defined as 1.00, that of patients of type A, B, C and D were 0.54, 0.58, 0.65 and 0.80 respectively. (2) The insulin sensitivity of patients in the 4 SDT groups were compared and no significant difference was found in comparison between group A, B and C, while significant difference was found when the other three groups were compared with group D (P<0.05), the insulin sensitivity of type D was close to that of the healthy subjects. (3) The fasting blood insulin of type D was obviously lower and the insulin sensitivity of type D was obviously higher than that of the other three types as a whole (P=0.0001). (4) Multivariate regression analysis demonstrated that insulin sensitivity was closely correlated with SDT (P=0.0001). Conclusion: Insulin resistance is one of the pathological basis for SDT in hypertension.

  13. Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome.

    Science.gov (United States)

    Enli, Yasar; Fenkci, Semin Melahat; Fenkci, Veysel; Oztekin, Ozer

    2013-12-01

    This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS.

  14. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Shou-Kui Xiang

    2012-01-01

    Full Text Available Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS. Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2, total testosterone (T, fasting glucose (FBG, fasting insulin (FINS, serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C, and low-density lipoprotein (LDL-C levels were checked, and then TG/HDL-C ratio, TC/HDL-C, ratio and LDL-C/HDL-C ratio were calculated. The homeostasis model assessment of insulin resistance (HOMA-IR was used to calculate the insulin resistance. Results. All lipoprotein ratios were significantly higher in PCOS patients as compared to healthy controls (<0.05. TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio were significantly correlated with HOMA-IR (<0.05. The ROC curve demonstrated that TC/HDL-C ratio had higher sensitivity and specificity in diagnosing PCOS with insulin resistance. Conclusion. This study demonstrates that serum lipoprotein ratio significantly correlates with insulin resistance and can be used as the marker of insulin resistance in PCOS patients.

  15. Accelerated aging syndromes, are they relevant to normal human aging?

    Science.gov (United States)

    Dreesen, Oliver; Stewart, Colin L

    2011-09-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? Much of what we know stems from the study of patient derived fibroblasts with both mutations resulting in increased DNA damage, primarily at telomeres. However, in vivo patients with Werner's develop arteriosclerosis, among other pathologies. In HGPS patients, including iPS derived cells from HGPS patients, as well as some mouse models for Progeria, vascular smooth muscle (VSM) appears to be among the most severely affected tissues. Defective Lamin processing, associated with DNA damage, is present in VSM from old individuals, indicating processing defects may be a factor in normal aging. Whether persistent DNA damage, particularly at telomeres, is the root cause for these pathologies remains to be established, since not all progeroid Lmna mutations result in DNA damage and genome instability.

  16. Glucose metabolism, insulin sensitivity and β-cell function in type A insulin resistance syndrome around puberty: a 9-year follow-up.

    Science.gov (United States)

    Huang, Z; Liu, J; Ma, L; Wan, X; He, X; Fang, D; Liao, Z; Li, Y

    2014-01-01

    Diabetes mellitus is thought to be progressive. Insufficient insulin secretion in compensation for insulin resistance leads to glucose intolerance. A previously reported proband with type A insulin resistance syndrome and her younger twin brothers with and without the R1174W missense mutation in the insulin receptor gene were followed for 9 years to study the progression of glucose metabolism, insulin sensitivity, and β-cell function around puberty. Five-hour OGTT was performed in them at each visit. Areas under the curves of glucose, insulin and C-peptides, insulinogenic index, AIR, and Homa indices were assessed. Intramyocellular lipids (IMCLs) were quantified in the proband and compared to those of 12 nondiabetic subjects, 118 newly diagnosed type 2 diabetic patients. The proband maintained normal HbA1c (27-37 mmol/mol) and fasting plasma glucose (3.7-4.5 mmol/l), and her glucose tolerance ameliorated over years. The proband's Homa-IR decreased into adulthood, while her Homa-B, insulinogenic index, AIR, AUCs of insulin, and C-peptide decreased accordingly. Homa-B to Homa-IR ratios stayed significantly higher than normal. Homa-B, AUCs of insulin, and C-peptide of the twin brothers increased in response to the increment of Homa-IR as they entered middle and late puberty. The changes were more dramatic in the twin brothers carrying the mutation. IMCLs of the proband were lower than those of the nondiabetic counterparts and were disproportional for the degree of insulin resistance. Our longitudinal data of type A insulin resistance syndrome around puberty provide significant information for the study of insulin secretion in compensation for insulin resistance.

  17. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Directory of Open Access Journals (Sweden)

    Rosa Lauretta

    2016-01-01

    Full Text Available Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold. Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis.

  18. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Science.gov (United States)

    Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

    2016-01-01

    Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

  19. Relationship between the Concentrations of Heavy Metals and Bioelements in Aging Men with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Iwona Rotter

    2015-04-01

    Full Text Available Heavy metals may exacerbate metabolic syndrome (MS but abnormal serum concentrations of bioelements may also co-exist with MS. The primary aim of the study was to assess the relationship of blood heavy metal and bioelement concentrations and MS, in men aged 50–75 years. Heavy metals—lead (Pb, cadmium (Cd, mercury (Hg, arsenic (As, tungsten (W, Macroelements—magnesium (Mg and calcium (Ca, and microelements—iron (Fe, zinc (Zn copper (Cu, chromium (Cr, molybdenum (Mo, selenium (Se and manganese (Mn, body mass index (BMI, waist to hip ratio (WHR, abdominal circumference (AC and blood pressure (BP, total cholesterol (TCh, high-density lipoprotein (HDL, low-density lipoprotein (LDL, triglyceride (TG, fasting plasma glucose (FPG, insulin, and Homeostasis Model Assessment—Insulin resistance (HOMA-IR. The men with MS showed statistically significant higher Zn and lower Mg concentrations. Those with diabetes had higher Ca concentration and lower Mg concentration. Cr and Mn concentrations were significantly higher in obese men. The participants with hypertension had lower Mg concentration. We found statistically significant positive correlations (W-TCh, W-LDL, Mg-TCh, Mg-LDL, Ca-TCh, Ca-LDL, Ca-insulin, Ca-HOMAR-IR, Zn-TG, Zn-insulin, Zn-HOMA-IR, Cu-BP systolic, Mn-BMI, Mn-AC, Mn-WHR, Mn-insulin, Mn-HOMA-IR, Se-TCh, Se-LDL, Se-TG, Se-insulin, Se-HOMA-IR, Cr-TCh, Cr-HDL, Cr-LDL, Cr-TG and negative correlations (Cd-insulin, Hg-WHR, W-insulin, W-HOMA-IR, Mg-BMI, Mg-AC, Mg-WHR, Mg-BP systolic, Mo-insulin, Mn-HDL. Tungsten may contribute to lipid disorders. Magnesium appears to play the protective role in the occurrence of metabolic disorders. Microelements Mn, Cr and Se may intensify MS.

  20. Metabolic syndrome, insulin resistance, and mammographic density in pre- and postmenopausal women.

    Science.gov (United States)

    Kim, Bo-Kyoung; Chang, Yoosoo; Ahn, Jiin; Jung, Hyun-Suk; Kim, Chan-Won; Yun, Kyung Eun; Kwon, Min-Jung; Suh, Byung-Seong; Chung, Eun Chul; Shin, Hocheol; Ryu, Seungho

    2015-09-01

    Little is known about the association of metabolic syndrome (MetS) or insulin resistance (IR) with mammographic density, a strong risk factor for breast cancer. The goal of this study was to evaluate these associations in pre- and postmenopausal women. A cross-sectional study was performed in 73,974 adult women who underwent a comprehensive health screening examination that included a mammogram between 2011 and 2013 (mean age 42.6 years). MetS was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III. IR was assessed with the homeostasis model assessment-insulin resistance (HOMA-IR). Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for dense breast were estimated using logistic regression models after adjustment for potential confounders. In premenopausal women, MetS and all its components except waist circumference were associated with dense breast. After adjustment for potential confounders, the OR (95% CI) for dense breast in women with MetS compared with those without MetS was 1.22 (1.06-1.39). In postmenopausal women, however, there was positive but non-significant association between MetS and dense breast. In both pre- and postmenopausal women, high blood glucose and IR were positively associated with dense breast. The OR (95% CI) for dense breast between the highest and lowest quartiles of HOMA-IR was 1.29 (1.20-1.39) for premenopausal women and 1.44 (1.05-1.97) for postmenopausal women. In a large sample of Korean women, MetS and IR were associated with mammographic dense breast, demonstrating that IR, a potentially modifiable risk factor, may increase breast cancer risk, possibly through high mammographic density.

  1. SOME FEATURES OF CYTOKINE PROFILE IN PATIENTS WITH GOUT AND INSULIN RESISTANCE SYNDROME

    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko

    2011-01-01

    Full Text Available Abstract. Blood serum levels of cytokines (Il-1β, TNFα, IL-2, IL-4, IL-6, IL-8, IL-10, IL-20, IL-23,  cytokine soluble receptors (SRp55 TNFα, SR IL-6, as well as markers of insulin resistance were studied in  a group of male patients with primary gout. Increased levels of the above cytokines and deficiency of soluble  IL-6 receptors in blood serum were most pronounced in gouty patients with insulin resistance syndrome. Close  links were revealed between serum uric acid and insulin contents in gouty patients. Significant correlations were  found between the levels of insulin, some cytokines (IL-4, IL-6, TNFα, and soluble receptors (SRp55 TNFα,  SR IL-6, thus presuming a certain role of impaired cytokine profile for development of insulin resistance  syndrome in such cohort of patients. (Med. Immunol., 2011, vol. 13, N 6, pp 627-630 

  2. Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver.

    Science.gov (United States)

    Furrer, J; Hättenschwiler, A; Komminoth, P; Pfammatter, T; Wiesli, P

    2001-05-01

    We report a patient with a hepatic neuroendocrine tumor showing an extraordinary change of the tumor's humoral manifestations from a clinically documented extrapituitary acromegaly and a typical carcinoid syndrome toward a hyperinsulinemic hypoglycemia syndrome. At the primary manifestation of the tumor, an increased serum level of insulin-like growth factor I due to overproduction of GHRH and an increased urinary excretion of 5-hydroxyindoleacetic acid were found. The clinical manifestation of the GHRH excess was an arthralgia, which resolved completely after operative tumor debulking and normalization of insulin-like growth factor I and GHRH serum levels. The secretion of serotonin from the tumor resulted in a typical carcinoid syndrome including right-sided valvular heart disease. On the later course of the disease, the humoral manifestations of the tumor were supplemented by the secretion of insulin, leading to recurrent severe hyperinsulinemic hypoglycemia. The hepatic origin of hyperinsulinism was demonstrated by selective arterial calcium stimulation. Moreover, tumor cells revealed insulin and C-peptide immunoreactivity in the immunohistochemical analysis. The patient died 8 yr after the initial diagnosis of the tumor, and a carefully performed autopsy procedure confirmed the absence of any extrahepatic tumor manifestation.

  3. Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women.

    Science.gov (United States)

    King, George A; Deemer, Sarah E; Thompson, Dixie L

    2012-12-01

    The purpose of this study was to examine insulin resistance, markers of the metabolic syndrome, cardiovascular disease (CVD) risk, and serum adiponectin concentrations in pre-menopausal Hispanic and non-Hispanic White (NHW) women. This cross-sectional study examined 119 pre-menopausal women (76 Hispanic, 45 NHW) for markers of the metabolic syndrome (ATP III criteria), level of insulin resistance (HOMA-IR), CVD risk factors, and serum total adiponectin concentrations. Relationships between variables were assessed using Student's t-tests, Pearson's and Spearman's Rho correlations, and stepwise multiple regression analysis. Hispanic women had significantly lower adiponectin concentrations than NHW women, even after controlling for body fat (%) (P women combined and for NHW women (P ≤ 0.04), but not for Hispanic women. Insulin resistance was inversely related to adiponectin for all women and for NHW women (P women. Adiponectin concentration was not significantly associated with number of CVD risk factors for these women. While adiponectin was associated with markers of metabolic syndrome and insulin resistance for all women of this study and despite lower adiponectin concentrations for Hispanic women than NHW women, the role of adiponectin to these conditions among Hispanics remains unclear. There was no significant association between adiponectin and CVD risk for these women. Future research should focus on understanding mechanisms for up-regulating adiponectin secretion and if ethnicity affects adiponectin gene expression and secretion given the beneficial effects derived from elevated adiponectin levels.

  4. Spironolactone in the treatment of polycystic ovary syndrome: effects on clinical features, insulin sensitivity and lipid profile.

    Science.gov (United States)

    Zulian, E; Sartorato, P; Benedini, S; Baro, G; Armanini, D; Mantero, F; Scaroni, C

    2005-01-01

    This prospective clinical trial was designed to assess the effects of a long-term therapy with spironolactone, with and without dietary-induced weight-loss, on clinical features, lipid profile and insulin levels in women with polycystic ovary syndrome (PCOS). Twenty-five patients (range of age 16-32 yr; 13 lean and 12 overweight) fulfilling formal diagnostic criteria for PCOS (oligomenorrhea and/or amenorrhea, biochemical and/or clinical evidence of hyperadrogenism) were studied at baseline and then received oral spironolactone (100 mg/die) for 12 months; association with lifestyle modifications was recommended to all over-weight patients. Clinical, endocrine and metabolic parameters [oral glucose tolerance test (OGTT), lipid profile] were measured at baseline and at the end of the antiandrogen treatment. The therapy was associated with a significant average decline of triglycerides in overweight subjects and with increased HDL-cholesterol levels in lean patients. The insulin levels at 60 min during OGTT, homeostasis model assessment-insulin resistance and area under curve of insulin were significantly lowered in overweight women after 12 months of spironolactone and weight loss and no negative changes in insulin secretion and sensitivity were observed in PCOS women after pharmacological treatment alone. The efficacy of spironolactone on the androgenic clinical aspects of PCOS has been confirmed in this study. Furthermore, our data show that long-term treatment with spironolactone exerts no negative effects on lipoprotein profile and glucose metabolism; more relevant beneficial effects on glucose and lipid metabolism were observed when the antiandrogen was associated with weight loss in overweight PCOS women.

  5. Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Aisa Ghaffarzad

    2016-05-01

    Full Text Available Background: Dyslipidemia and insulin resistance (IR, occurring in most infertile women with polycystic ovarian syndrome (PCOS, increase the risk of cardiovascular disease (CVD and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Materials and Methods: Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu, insulin and lipid profile levels [triglycerides (TGs, total cholesterol (TC, low-density lipoproteincholesterol (LDL-C and high-density lipoprotein-cholesterol (HDL-C] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C were calculated. IR was also calculated using homeostasis model assessment (HOMA-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC curve analysis using the area under curve (AUC. Results: Waist circumference (WC, insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19 as a marker of IR in infert ile PCOS women. Conclusion: Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR in infertile PCOS patients.

  6. Effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome patients with insulin resistance

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To investigate the effects of pioglitazone on serum leptin and adiponectin in polycystic ovary syndrome(PCOS)patients with insulin resistance(IR).Methods Thirty-five PCOS patients with IR were treated with pioglitazone 15mg/d for 12 weeks.The results of ovulation induction were observed.The changes of fasting plasma glucose(FPG),fasting serum insulin(FINS),serum levels of leptin,adiponectin,follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T)and blood fat were examined at the ...

  7. Neck circumference as a predictor of metabolic syndrome, insulin resistance and low-grade systemic inflammation in children: the ACFIES study

    OpenAIRE

    Gomez-Arbelaez, Diego; Camacho, Paul Anthony; Cohen, Daniel Dylan; Saavedra-Cortes, Sandra; Lopez-Lopez, Cristina; Lopez-Jaramillo, Patricio

    2016-01-01

    Background The current study aims to evaluate the association between neck circumference (NC) and several cardio-metabolic risk factors, to compare it with well-established anthropometric indices, and to determine the cut-off point value of NC for predicting children at increased risk of metabolic syndrome, insulin resistance and low-grade systemic inflammation. Methods A total of 669 school children, aged 8–14, were recruited. Demographic, clinical, anthropometric and biochemical data from a...

  8. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

  9. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    Directory of Open Access Journals (Sweden)

    Abimbola A. Akintola

    2015-05-01

    Full Text Available Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families (offspring and controls; and age categories thereof. From the Leiden Longevity Study, 132 participants underwent oral glucose tolerance test to assess glycemia (fasted glucose and glucose area-under-the-curve (AUC, insulin resistance (fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR, and pancreatic Beta cell secretory capacity (insulinogenic index. 3Tesla MRI and Magnetization Transfer (MT imaging MT-ratio peak-height was used to quantify differences in microstructural brain parenchymal tissue homogeneity that remain invisible on conventional MRI. Analyses were performed in offspring and age-matched controls, with and without stratification for age.In the full offspring group only, reduced peak-height in grey and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p65 years: in younger controls, significantly stronger inverse associations were observed between peak-height and fasted glucose, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in grey matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction<0.05. Although the strength of the associations tended to attenuate with age in the offspring group, the difference between age groups was not statistically significant. Thus, associations between impaired insulin action and reduced microstructural brain parenchymal tissue homogeneity were stronger in offspring compared to controls, and seemed to diminish with age.

  10. Significance of an index of insulin resistance on admission in non-diabetic patients with acute coronary syndromes

    OpenAIRE

    Stubbs, P.; Alaghband-Zadeh, J; Laycock, J.; Collinson, P.; Carter, G.; Noble, M.

    1999-01-01

    BACKGROUND—Insulin resistance is associated with ischaemic heart disease and has been proposed as a risk factor for subsequent myocardial infarction.
AIM—To investigate the potential use of a recently proposed insulin resistance index in identifying insulin resistance in patients admitted with an acute coronary syndrome.
METHODS—Single centre study of 441 non-diabetic patients admitted with chest pain to a coronary care unit and followed prospectively for a median of three years for outcome. ...

  11. Normal weight obesity is associated with metabolic syndrome and insulin resistance in young adults from a middle-income country.

    Directory of Open Access Journals (Sweden)

    Francilene B Madeira

    Full Text Available OBJECTIVE: This population-based birth cohort study examined whether normal weight obesity is associated with metabolic disorders in young adults in a middle-income country undergoing rapid nutrition transition. DESIGN AND METHODS: The sample involved 1,222 males and females from the 1978/79 Ribeirão Preto birth cohort, Brazil, aged 23-25 years. NWO was defined as body mass index (BMI within the normal range (18.5-24.9 kg/m(2 and the sum of subscapular and triceps skinfolds above the sex-specific 90th percentiles of the study sample. It was also defined as normal BMI and % BF (body fat >23% in men and >30% in women. Insulin resistance (IR, insulin sensitivity and secretion were based on the Homeostasis Model Assessment (HOMA model. RESULTS: In logistic models, after adjusting for age, sex and skin colour, NWO was significantly associated with Metabolic Syndrome (MS according to the Joint Interim Statement (JIS definition (Odds Ratio OR = 6.83; 95% Confidence Interval CI 2.84-16.47. NWO was also associated with HOMA2-IR (OR = 3.81; 95%CI 1.57-9.28, low insulin sensitivity (OR = 3.89; 95%CI 2.39-6.33, and high insulin secretion (OR = 2.17; 95%CI 1.24-3.80. Significant associations between NWO and some components of the MS were also detected: high waist circumference (OR = 8.46; 95%CI 5.09-14.04, low High Density Lipoprotein cholesterol (OR = 1.65; 95%CI 1.11-2.47 and high triglyceride levels (OR = 1.93; 95%CI 1.02-3.64. Most estimates changed little after further adjustment for early and adult life variables. CONCLUSIONS: NWO was associated with MS and IR, suggesting that clinical assessment of excess body fat in normal-BMI individuals should begin early in life even in middle-income countries.

  12. Exercise in aging: its important role in mortality, obesity and insulin resistance

    Science.gov (United States)

    Ryan, Alice S

    2011-01-01

    The prevalence of overweight and obesity has increased dramatically over the last several decades. Obesity and physical inactivity increase the risk for cardiovascular disease, Type 2 diabetes mellitus, hypertension, dyslipidemia and certain cancers. Obesity and low levels of physical fitness are also associated with increased risk of all-cause and cardiovascular mortality. Central and total obesity, insulin resistance and inactivity increase with age. Exercise training and increased fitness promote positive changes in body composition and improve insulin sensitivity. This article will describe the effects of exercise training, both aerobic and resistive, on body composition and obesity as well as review studies investigating the effects of exercise training on glucose metabolism and insulin sensitivity in older adults. Adopting a physically active lifestyle should be emphasized in overweight and obese individuals with insulin resistance to reduce the risk for cardiovascular events in the aging population. PMID:21359160

  13. Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults

    Science.gov (United States)

    The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, andMetSrisk and whether plasma fatty acids,...

  14. The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

    Science.gov (United States)

    El-Koofy, Nehal M.; Anwar, Ghada M.; El-Raziky, Mona S.; El-Hennawy, Ahmad M.; El-Mougy, Fatma M.; El-Karaksy, Hanaa M.; Hassanin, Fetouh M.; Helmy, Heba M.

    2012-01-01

    Background/Aim: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD. PMID:22249092

  15. The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children

    Directory of Open Access Journals (Sweden)

    Nehal M El-Koofy

    2012-01-01

    Full Text Available Background/Aim: To study the prevalence of metabolic syndrome (MS, insulin resistance (IR and non-alcoholic fatty liver disease (NAFLD in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT. Patients and Methods: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG, total cholesterol, high-density lipoprotein cholesterol (HDL-c, low-density lipoprotein cholesterol (LDL-c and liver biochemical profile, in addition to liver ultrasound and liver biopsy. Results: Twenty patients (60.6% were labeled with MS. IR was present in 16 (48.4%. Fifteen (44% patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001. Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05 and fitted more with the criteria of MS (80% vs. 44%. IR was significantly more common among NAFLD patients (73% vs. 28%. Conclusion: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

  16. Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

    Directory of Open Access Journals (Sweden)

    Courtney eScerbak

    2014-07-01

    Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

  17. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

    Science.gov (United States)

    Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

    2014-06-01

    In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

  18. Relationship of PGC-1α gene polymorphism with insulin resistance syndrome in Korean children.

    Science.gov (United States)

    Ha, Chang-Duk; Cho, Jin-Kyung; Han, Taekyung; Lee, Shin-Ho; Kang, Hyun-Sik

    2015-03-01

    This study aimed to investigate the associations between peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) gene Gly482Ser polymorphism (rs8192678) and parameters of insulin resistance in a sample of Korean children. A total of 286 children aged 10 to 12 years old were recruited from local elementary schools. Measured variables included body fat, blood pressures, blood lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and accelerometer-based physical activity (PA). Significant differences in percentage body fat (P = .016), insulin (P = .013), and HOMA-IR (P = .007) were found according to Gly482Ser genotype, with no significant genotype differences in the other measured variables. The genotype-specific differences in insulin (P = .136) and HOMA-IR (P = .067) were significantly attenuated when adjusted for age, sex, Tanner stage, body fat, and PA. The findings of the study suggest that the genetic effects of the PGC-1α genotypes on parameters of insulin resistance might be modulated by lifestyle factors, including PA and body fatness.

  19. Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome?

    Science.gov (United States)

    Corbould, A

    2008-10-01

    Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia in women. The objective was to review evidence for the converse situation, i.e. whether androgens adversely influence insulin action. Androgen excess could potentially contribute to the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in obese peripubertal girls. An Entrez-PubMed search was conducted to identify studies addressing the relationship of androgens with metabolic syndrome/type 2 diabetes in women. Studies reporting outcomes of androgen administration, interventions to reduce androgen effects in hyperandrogenemic women, and basic studies investigating androgen effects on insulin target tissues were reviewed. Multiple studies showed associations between serum testosterone and insulin resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross-sectional nature did not allow conclusions about causality. Androgen administration to healthy women was associated with development of insulin resistance. Intervention studies in women with hyperandrogenism were limited by small subject numbers and use of indirect methods for assessing insulin sensitivity. However, in three of the seven studies using euglycemic hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen action improved insulin sensitivity. Testosterone administration to female rats caused skeletal muscle insulin resistance. Testosterone induced insulin resistance in adipocytes of women in vitro. In conclusion, the metabolic consequences of androgen excess in women have been under-researched. Studies of long-term interventions that lower androgen levels or block androgen effects in young women with hyperandrogenism are needed to determine whether these might protect against metabolic syndrome/type 2 diabetes in later life.

  20. Cinnamon: Potential Role in the Prevention of Insulin Resistance, Metabolic Syndrome, and Type 2 Diabetes

    OpenAIRE

    Qin, Bolin; Panickar, Kiran S.; Anderson, Richard A.

    2010-01-01

    Metabolic syndrome is associated with insulin resistance, elevated glucose and lipids, inflammation, decreased antioxidant activity, increased weight gain, and increased glycation of proteins. Cinnamon has been shown to improve all of these variables in in vitro, animal, and/or human studies. In addition, cinnamon has been shown to alleviate factors associated with Alzheimer's disease by blocking and reversing tau formation in vitro and in ischemic stroke by blocking cell swelling. In vitro s...

  1. Age associated differences in prevalence of individual rotterdam criteria and metabolic risk factors during reproductive age in 446 caucasian women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Glintborg, D; Mumm, H; Ravn, P;

    2012-01-01

    Clinical manifestations and metabolic risk factors may differ according to age in patients with polycystic ovary syndrome (PCOS). Therefore, a retrospective trans-sectional study in academic tertiary-care medical center was designed. A cohort of 446 premenopausal, Caucasian women (age range 15......, fasting lipids, insulin, glucose), transvaginal ultrasound, oral glucose tolerance tests (OGTT) (n=234), and ACTH tests (n=201). BMI, waist, Ferriman-Gallwey score, blood pressure, and lipid profile were higher in older vs. younger age groups whereas androgen levels were lower. Measures of insulin...... resistance were unchanged between age groups, but glucose levels were significantly higher in older age groups. Rotterdam criteria: The prevalence of PCO and biochemical hyperandrogenism decreased in the oldest age group whereas clinical hyperandrogenism increased. Young patients are characterized by PCO...

  2. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR, and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

  3. Overweight, obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy.

    Science.gov (United States)

    Łuczyński, Włodzimierz; Szypowska, Agnieszka; Głowińska-Olszewska, Barbara; Bossowski, Artur

    2011-07-01

    There has been no specific evaluation of atherogenic risk factors in children with type 1 diabetes mellitus (T1DM) treated with continuous subcutaneous insulin infusion (CSII). We, therefore, studied the prevalence of overweight/obesity and metabolic syndrome among these patients. Five hundred children with T1DM treated with CSII and multiple daily insulin (MDI) regimen were included in the study. Anthropometric data/physical examination, data concerning diabetes, and a lipid profile were assessed in this group, and compared with respect to treatment method (CSII vs. MDI). Almost one-third (30.2%) of the children were overweight/obese. The body mass index (BMI) values at the time of the present evaluation were significantly higher in comparison with the BMI values 3-6 months after the diagnosis. Dyslipidemia was recognized in 51.6%, hypertension in 4.8%, and the metabolic syndrome in 3.2%. of the subjects. The overweight/obese children differed from their normal-weight counterparts with respect to metabolic control, the incidence of hypertension, dyslipidemia, and metabolic syndrome. The girls showed higher prevalence of overweight/obesity and higher BMI values compared to the boys. The children treated with CSII had the same prevalence of overweight/obesity, but a lower incidence of dyslipidemia, and a better metabolic control compared to the children treated with MDI regimen. Our study shows a high prevalence of overweight/obesity and dyslipidemia in children with T1DM including those treated with an insulin pump.

  4. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  5. Acute coronary syndromes: an old age problem

    Institute of Scientific and Technical Information of China (English)

    Alexander D Simms; Philip D Batin; John Kurian; Nigel Durham; Christopher P Gale

    2012-01-01

    The increasing population in older age will lead to greater numbers of them presenting with acute coronary syndromes (ACS). This has implications on global healthcare resources and necessitates better management and selection for evidenced-based therapies. The elderly are a high risk group with more significant treatment benefits than younger ACS. Nevertheless, age related inequalities in ACS care are recognised and persist. This discrepancy in care, to some extent, is explained by the higher frequency of atypical and delayed presentations in the elderly, and less diagnostic electrocardiograms at presentation, potentiating a delay in ACS diagnosis. Under estimation of mortality risk in the elderly due to limited consideration for physiological frailty, co-morbidity, cognitive/psychological impairment and physical disability, less input by cardiology specialists and lack of randomised, controlled trials data to guide management in the elderly may further confound the inequality of care. While these inequalities exist, there remains a substantial opportunity to improve age related ACS outcomes. The selection of elderly patients for specific therapies and medication regimens are unanswered. There is a growing need for randomised, controlled trial data to be more representative of the population and enroll those of advanced age with co-morbidity. A lack of reporting of adverse events, such as renal impairment post coronary angiography, in the elderly further limit risk benefit decisions. Substantial improvements in care of elderly ACS patients are required and should be advocated. Ultimately, these improvements are likely to lead to better outcomes post ACS. However, the improvement in outcome is not infinite and will be limited by non-modifiable factors of age-related risk.

  6. The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome.

    Science.gov (United States)

    Selimoglu, H; Duran, C; Kiyici, S; Ersoy, C; Guclu, M; Ozkaya, G; Tuncel, E; Erturk, E; Imamoglu, S

    2010-04-01

    Insulin resistance (IR) is one of the common features of the polycystic ovary syndrome (PCOS), and recent studies indicate the possible role of vitamin D in the pathogenesis of IR and glucose metabolism. Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and androgen levels in obese, insulin-resistant women with PCOS. Eleven women with PCOS were included in the study. Mean age of the patients was 23.6+/-5.7 yr, body mass index 33.9+/-5.1 kg/m(2). Six patients (54.5%) had acantosis nigricans and 10 (90.9%) oligoamenorrhea. The mean Ferriman Gallwey score was 14.1+/-4.6. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D3 orally, 25-hydroxyvitamin D3 significantly increased from 16.9+/-16 ng/ml to 37.1+/-14.6 ng/ml (p: 0.027) and only 2 women were detected to have vitamin D3 levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assessment (HOMA)-IR significantly decreased from 4.41+/-1.38 to 3.67+/-1.48 (p: 0.043). No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. No correlation was found between vitamin D with HOMA and other hormonal parameters. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a beneficial effect on IR in obese women with PCOS.

  7. Progeria syndromes and ageing: what is the connection?

    Science.gov (United States)

    Burtner, Christopher R; Kennedy, Brian K

    2010-08-01

    One of the many debated topics in ageing research is whether progeroid syndromes are really accelerated forms of human ageing. The answer requires a better understanding of the normal ageing process and the molecular pathology underlying these rare diseases. Exciting recent findings regarding a severe human progeria, Hutchinson-Gilford progeria syndrome, have implicated molecular changes that are also linked to normal ageing, such as genome instability, telomere attrition, premature senescence and defective stem cell homeostasis in disease development. These observations, coupled with genetic studies of longevity, lead to a hypothesis whereby progeria syndromes accelerate a subset of the pathological changes that together drive the normal ageing process.

  8. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  9. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  10. Distribution of Serum Total Homocysteine and Its Association with Diabetes and Cardiovascular Risk Factors of the Insulin Resistance Syndrome in Mexican American Men: The Third National Health and Nutrition Examination Survey

    Directory of Open Access Journals (Sweden)

    Gillum Richard

    2003-08-01

    Full Text Available Abstract Background Few data have been published on the association of variables of the insulin resistance syndrome and serum total homocysteine (tHcy, a putative risk factor for cardiovascular morbidity, in representative samples of total populations or in Hispanic Americans. Methods To describe the distributions of serum tHcy concentration and variables associated with insulin resistance in Mexican American men and to assess their association, data from a cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey were analyzed. Analyses were restricted to Mexican American men aged 40–74 years with data on glycated hemoglobin (%, body mass index (BMI, body fat distribution, HDL cholesterol, fasting serum insulin, serum triglycerides and serum tHcy concentrations. Results Cumulative distributions of serum tHcy shifted to the right with increasing age. Log serum tHcy was not associated with prevalence of diagnosed diabetes mellitus or glycated hemoglobin percent or other risk factors other than age. Log serum tHcy concentration showed borderline significant (p = 0.049 positive association with fasting serum insulin concentration independent of age and BMI, only in men aged 60–74. Conclusion No consistent association of tHcy with diabetes prevalence or variables of the insulin resistance syndrome were found in Mexican American men aged 40–74 years. Further research is needed on the associations of serum tHcy concentration with insulin resistance and other components of the insulin resistance syndrome in persons of varying ethnicity.

  11. Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study.

    Science.gov (United States)

    Fernandez-Real, José-Manuel; Pugeat, Michel; Grasa, Mar; Broch, Montserrat; Vendrell, Joan; Brun, Jocelyne; Ricart, Wifredo

    2002-10-01

    It has been suggested that a low grade inflammatory state could predispose for developing insulin resistance and contribute to the development of obesity and type 2 diabetes. Corticosteroid-binding globulin (CBG), the main plasma protein transport for cortisol, has been shown to be negatively regulated by insulin and IL-6, at least in vitro, suggesting that insulin resistance and inflammation may both contribute to decreasing CBG levels. In the present study we measured CBG concentrations in a human healthy population and investigated the relationships of CBG with anthropometric and biochemical markers for inflammation and/or insulin resistance. The data showed that the mean serum CBG level was significantly lower in males (n = 151) than in females (n = 113; 32.5 +/- 9.1 vs. 39.2 +/- 13.9 mg/liter; P fasting cortisol/CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age. BMI (P < 0.0001), free cortisol (P = 0.003), and CBG (P = 0.009), but not WHR and age, contributed to 20%, 6%, and 8%, respectively, of HOMA variance in women in a multiple regression analysis. In this model only BMI (P < 0.0001) independently contributed to HOMA variance in men. These findings support the hypothesis that the CBG level is an interesting indicator for both insulin resistance and low grade inflammation. Whether the decrease in CBG levels is genetic by nature or directly associated to increased insulin and/or IL-6 merits further investigation. Nevertheless, because CBG has been shown to be expressed by the adipose tissue, decreased CBG could create locally increased cortisol disposal, with no change in circulating cortisol, and facilitate fat accumulation, insulin resistance, and type 2 diabetes.

  12. Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Israel Pérez-Torres

    2016-10-01

    Full Text Available The antioxidant properties of aged garlic extract (AGE on cardiovascular functioning (CF in metabolic syndrome (MS remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS, MS rats (30% sucrose in drinking water from weaning plus saline solution (MS + SS, control rats receiving AGE (C + AGE 125 mg/Kg/12 h and MS rats with AGE (MS + AGE were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01. Cholesterol was decreased by AGE (p = 0.05. Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05. Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001. Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation and AGE improved it (p = 0.001. Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001. Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01. In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.

  13. Leukocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Phelan, N

    2012-06-20

    OBJECTIVES: Low-grade chronic inflammation predicts cardiovascular outcomes and is observed in women with polycystic ovary syndrome (PCOS). Whether this is entirely a cause or consequence of insulin resistance (IR) is unknown. METHODS: Seventy pairs of women with and without PCOS, matched for age, BMI and IR (HOMA, QUICKI and Avignon index), were generated from a larger cohort of 103 women with and 104 BMI-matched women without PCOS. Women with PCOS were studied in the follicular phase of the menstrual cycle. White cell count (WCC), high-sensitivity CRP (hsCRP) and a series of 12 cytokines and growth factors were measured. These inflammatory markers were also compared between women with PCOS and 10 normal women studied in the follicular, peri-ovulatory and luteal stages. RESULTS: When all subjects were compared, WCC (6.75 x 10(9) vs 5.60 x 10(9) g\\/l, p<0.005), hsCRP (4.04 vs 2.90 mg\\/l, p<0.05), and IL-6 (1.11 vs 0.72 pg\\/ml, p<0.05) were greater in women with PCOS. Pair-matching for IR eliminated between-group differences in hsCRP and cytokines but did not alter the difference in WCC (6.60 x 10(9) vs 5.60 x 10(9) g\\/l, p<0.005). WCC was greater in PCOS compared to normal women at all stages of the menstrual cycle. CONCLUSIONS: Low-grade inflammation occurs in PCOS. Increased hsCRP and cytokines are associated with IR but increased WCC is observed even when IR is accounted for. The explanation for this and its clinical significance is unknown. © 2012 Blackwell Publishing Ltd.

  14. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8)

    OpenAIRE

    Cuesta, Sara; Kireev, Roman; García, Cruz; Rancan, Lisa; Vara, Elena; Jesús A. F. Tresguerres

    2012-01-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was d...

  15. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency.

    Science.gov (United States)

    Ardabili, Hania R; Gargari, Bahram P; Farzadi, Laya

    2012-03-01

    Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

  16. Study of Androgen and Androgen Receptor in Relation to Insulin Resistance in Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    初永丽; 孙永玉; 邱红玉

    2003-01-01

    In order to investigate the relationship between serum testosterone level and expression of androgen receptors in ovary in relation to insulin resistance in polycystic ovary syndrome (PCOS). Serum testosterone levels were determined by radioimmunoassay in 17 patients with PCOS and 20 cases as control group. The expression of androgen receptor in ovary was detected by immunohistochemistry method. The results showed that serum testosterone level [ (3. 1± 1.5) nmol/L] and insulin resistance index (0. 85±0. 49) in patients with PCOS were significantly higher than in control group (P<0. 05), and showed a positive relation (r=0. 65, P<0. 01). The expression levels of androgen receptor in ovary of patients with PCOS were significantly higher than that in control group (P<0.05). The optical density value was positively related with insulin resistance index (r=0.59,P<0. 01). It was concluded that androgen and androgen receptor could accelerate insulin resistance and the interaction of them might aggravate the pathophysiological change in PCOS.

  17. Vascular wall dysfunction in JCR:LA-cp rats: effects of age and insulin resistance.

    Science.gov (United States)

    O'brien, S F; Russell, J C; Davidge, S T

    1999-11-01

    We tested the hypothesis that aging and insulin resistance interact to increase vascular dysfunction by comparing the function of isolated mesenteric resistance arteries in obese, insulin-resistant JCR:LA-cp rats and lean, insulin-sensitive rats of the same strain at 3, 6, 9, and 12 mo of age. The peak constrictor responses to norepinephrine, phenylephrine, and high potassium were elevated in arteries from obese rats. Responses to these agents increased with age in both obese and lean rats. An eicosanoid constrictor contributed substantially to vasoconstriction in the arteries from both lean and obese animals. Inhibition of nitric oxide synthase increased the vasoconstrictor response to norepinephrine in both obese and lean rats. This effect increased with age in lean rats only. Vascular relaxation in response to acetylcholine and sodium nitroprusside was impaired in the obese rats and did not alter with age. The results suggest that obese JCR:LA-cp rats have enhanced maximal constriction, which originates in the arterial smooth muscle and increases with age. There is evidence that the ability of the arteries to compensate for the enhanced contractility is impaired in obese rats, particularly with advanced age.

  18. Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students

    Directory of Open Access Journals (Sweden)

    José Bonifácio Barbosa

    2016-04-01

    Full Text Available Abstract A cross-sectional population-based study using questionnaire and anthropometric data was conducted on 968 university students of São Luís, Brazil, from which 590 showed up for blood collection. In the statistical analysis the Student t-test, Mann-Whitney and chi-square tests were used. The prevalence of metabolic syndrome by the Joint Interim Statement (JIS criteria was 20.5%, almost three times more prevalent in men (32.2% than in women (13.5% (P < 0.001. The prevalence of insulin resistance was 7.3% and the prevalence of low HDL-cholesterol was high (61.2%, both with no statistically significant differences by sex. Men showed a higher percentage of smoking, overweight, high blood pressure, high blood glucose and increased fasting hypertriglyceridemia. Women were more sedentary. University students of private institutions had higher prevalences of sedentary lifestyle, obesity, abdominal obesity, elevated triglycerides and metabolic syndrome than students from public institutions. High prevalences of metabolic syndrome, insulin resistance and other cardiovascular risk factors were found in this young population. This suggests that the burden of these diseases in the future will be increased.

  19. Correlation between myostatin and obesity or insulin resistance of patientswith polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    Zhai Lu; Hua Chen; Man-Ling Chen; Song Jin; Yue-Ping Li

    2015-01-01

    Objective: To study the correlated relationship between the myostatin level and the obesity, insulin resistance of patients with polycystic ovary syndrome. Methods: Based on cross-sectional case-control study, 165 polycystic ovary syndrome patients were divided into obese group and no-obese group.At the same time, 142 healthy women were chosen as the control group. The level of fasting glucose, fasting insulin, HOMA-IR (the index of insulin resistance), BMI, waist circumference, waist-hip ratio and the level of sex hormone were determined and compared between the control group and non-obese PCOS group, between the obese and non-obese PCOS group. The correlation between MSTN and the indicator above was analyzed by regression analysis. Results:Compared with the control group, the MSTN level was significantly higher in the patients with PCOS(18.71±15.54 vs. 14.0±15.22, P=0.014), but there was no significant difference between non-obese PCOS group and the control group, excluding the obesity factor. The result of regression analysis showed that the MSTN level was significantly related to the waist circumference, waist-hip ratio, BMI and the testosterone level. After adjusting the BMI and testosterone, the mutivariate regression analysis showed that the MSTN level was significantly related to the PCOS present. And our study did not show the correlation between the MSTN level and the insulin resistance in PCOS patients, while the latter was closely related to the occurrence and progression of PCOS. Conclusion: The MSTN level is significantly related to waist circumference, waist-hip ratio, BMI and the testosterone level.And the MSTN level is also significantly related to the PCOS present.

  20. A defect in the activity of Delta6 and Delta5 desaturases may be a factor predisposing to the development of insulin resistance syndrome.

    Science.gov (United States)

    Das, Undurti N

    2005-05-01

    GLUT-4 (glucose transporter) receptor, tumor necrosis factor-alpha (TNF-alpha), interleukins-6 (IL-6), daf-genes and PPARs (peroxisomal proliferation activator receptors) play a role in the development of insulin resistance syndrome and associated conditions. But, the exact interaction between these molecules/factors and the mechanism(s) by which they produce insulin resistance syndrome is not clear. I propose that a defect in the activity of the enzymes Delta6 and Delta5 desaturases that are essential for the formation of long chain metabolites of essential fatty acids, linoleic acid and alpha-linolenic acid, is a factor in the development of insulin resistance syndrome. Long chain polyunsaturated fatty acids (LCPUFAs) increase cell membrane fluidity and enhance the number of insulin receptors and the affinity of insulin to its receptors; suppress TNF-alpha, IL-6, macrophage migration inhibitory factor (MIF) and leptin synthesis; increase the number of GLUT-4 receptors, serve as endogenous ligands of PPARs, modify lipolysis, and regulate the balance between pro- and anti-oxidants, and thus, play a critical role in the pathogenesis of insulin resistance. In the nematode, Caenorhabditis elegans, the protein encoded by daf-2 is 35% identical to the human insulin receptor; daf-7 codes a transforming growth factor-beta (TGF-beta) type signal and daf-16 enhances superoxide dismutase (SOD) expression. Melatonin has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Calorie restriction enhances the activity of Delta6 and Delta5 desaturases, melatonin production, decreases daf-2 signaling, free radical generation, and augments anti-oxidant defenses that may explain the beneficial effect of diet control in the management of obesity, insulin resistance, and type II diabetes mellitus. These evidences suggest that the activities of Delta6 and Delta5 enzymes play a critical role in the expression and regulation of GLUT-4, TNF-alpha, IL-6, MIF, daf-genes, melatonin, and

  1. IMPACT OF ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM ON THE DEVELOPMENT OF INSULIN RESISTANCE SYNDROME

    Directory of Open Access Journals (Sweden)

    G. E. Roitberg

    2014-07-01

    Full Text Available Objective: to analyze the distribution of components of insulin resistance (IR syndrome and to study the frequency of their combinations in relation to the genotypes and allelic variants of the angiotensin-converting enzyme (ACE gene.Subjects and methods. A group of clinically healthy patients (50 women and 42 men with different genotypes of the ACE gene was examined.The distribution of IR syndrome components and the frequency of their combinations were analyzed in relation to the genotypes and allelicvariants of the ACE gene.Results. A group of D allele carriers compared to A allele ones showed a pronounced tendency for the frequency of IR to reduce due to thehigher proportion of patients with complete IR syndrome. This observation becomes statistically significant in the assessment of homozygous variants of the ACE gene. At the same time dyslipidemia and hypertension in the presence of IR significantly more frequently occurred in patients with the DD genotype than in those with genotype II.Conclusion. There was a marked predominance of the manifestations of IR syndrome with a complete set of components in the DD genotypicgroup, which confirms the significant strong association between ACE gene polymorphism and IR syndrome.

  2. IMPACT OF ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM ON THE DEVELOPMENT OF INSULIN RESISTANCE SYNDROME

    Directory of Open Access Journals (Sweden)

    G. E. Roitberg

    2013-01-01

    Full Text Available Objective: to analyze the distribution of components of insulin resistance (IR syndrome and to study the frequency of their combinations in relation to the genotypes and allelic variants of the angiotensin-converting enzyme (ACE gene.Subjects and methods. A group of clinically healthy patients (50 women and 42 men with different genotypes of the ACE gene was examined.The distribution of IR syndrome components and the frequency of their combinations were analyzed in relation to the genotypes and allelicvariants of the ACE gene.Results. A group of D allele carriers compared to A allele ones showed a pronounced tendency for the frequency of IR to reduce due to thehigher proportion of patients with complete IR syndrome. This observation becomes statistically significant in the assessment of homozygous variants of the ACE gene. At the same time dyslipidemia and hypertension in the presence of IR significantly more frequently occurred in patients with the DD genotype than in those with genotype II.Conclusion. There was a marked predominance of the manifestations of IR syndrome with a complete set of components in the DD genotypicgroup, which confirms the significant strong association between ACE gene polymorphism and IR syndrome.

  3. Small for Gestational Age and Magnesium in Cord Blood Platelets: Intrauterine Magnesium Deficiency May Induce Metabolic Syndrome in Later Life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2011-01-01

    Full Text Available Magnesium deficiency in pregnancy frequently occurs because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have disclosed that small for gestational age (SGA is associated with an increased risk of insulin resistance in adult life. We reported that intracellular magnesium of cord blood platelets is lower in SGA groups than that in appropriate for gestational age groups, suggesting that intrauterine magnesium deficiency may result in SGA. Taken together, intrauterine magnesium deficiency in the fetus may lead to or at least program insulin resistance after birth. In this review, we propose that intrauterine magnesium deficiency may induce metabolic syndrome in later life. We discuss the potential contribution of aberrant magnesium regulation to SGA and to the pathogenesis of metabolic syndrome.

  4. Hypertension Is a Key Feature of the Metabolic Syndrome in Subjects Aging with HIV

    DEFF Research Database (Denmark)

    Martin-Iguacel, Raquel; Negredo, Eugènia; Peck, Robert

    2016-01-01

    to predispose to these metabolic complications and to the excess risk of CVD observed in the HIV population. The metabolic syndrome (MS) represents a clustering of RF for CVD that includes abdominal obesity, hypertension, dyslipidemia and insulin resistance. Hypertension is a prevalent feature of the MS in HIV......With widespread and effective antiretroviral therapy, the life expectancy in the HIV population has dramatically improved over the last two decades. Consequently, as patients are aging with HIV, other age-related comorbidities, such as metabolic disturbances and cardiovascular disease (CVD), have......, in particular in the aging population, and constitutes an important RF for CVD. Physicians should screen their patients for metabolic and cardiovascular risk at the regular visits to reduce MS and the associated CVD risk among people aging with HIV, since many of RF are under-diagnosed and under...

  5. Leptin, Ghrelin, Adiponectin, Homocysteine and Insulin Resistance Related to Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Saghar Salehpour

    2009-01-01

    Full Text Available The relationship between leptin, adiponectin, ghrelin, homocysteine, insulin resistance andother biochemical factors in women with polycystic ovary syndrome (PCOS is controversial.We review how the expanded role of these factors in reproduction might impact ourunderstanding of PCOS. For purposes of our review, we accessed the PUBMED databaseduring the past 10 years. Our review confirms that these factors can have etiopathogeneticimportance in some enigmatic reproductive disturbances such as PCOS. Moreoverunderstanding the role of these biochemical factors might be useful for new treatments inPCOS.

  6. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2007-01-01

    Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism,...

  7. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome

    OpenAIRE

    Kim, Bhumsoo; Feldman, Eva L.

    2015-01-01

    Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and ...

  8. Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS.

    LENUS (Irish Health Repository)

    Phelan, N

    2012-02-01

    OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are more insulin resistant and display an atherogenic lipid profile compared with normal women of similar body mass index (BMI). Insulin resistance (IR) at least partially underlies the dyslipidemia of PCOS, but it is unclear whether PCOS status per se confers additional risk. RESEARCH DESIGN AND METHODS: Using a case-control design, we compared plasma lipids and lipoprotein subclasses (using polyacrylamide gel tube electrophoresis) in 70 women with PCOS (National Institutes of Health criteria) and 70 normal women pair matched for age, BMI, and IR (homeostasis model assessment-IR, quantitative insulin sensitivity check index, and the Avignon Index). Subjects were identified as having a (less atherogenic) type A pattern consisting predominantly of large low-density lipoprotein (LDL) subfractions or a (more atherogenic) non-A pattern consisting predominantly of small-dense LDL subfractions. RESULTS: Total, high-density lipoprotein, or LDL cholesterol, or triacylglycerol did not differ between the groups, but very low-density lipoprotein levels (P<0.05) were greater in women with PCOS, whereas a non-A LDL profile was seen in 12.9% compared with 2.9% of controls (P<0.05, chi2). Multiple regression analysis revealed homeostasis model assessment-IR and waist circumference to be independent predictors of very low-density lipoprotein together explaining 40.2% of the overall variance. Logistic regression revealed PCOS status to be the only independent determinant of a non-A LDL pattern (odds ratio 5.48 (95% confidence interval 1.082-27.77; P<0.05). CONCLUSIONS: Compared with women matched for BMI and IR, women with PCOS have potentially important differences in lipid profile with greater very low-density lipoprotein levels and increased rates of a more atherogenic non-A LDL pattern.

  9. Identification of Differentially Expressed MicroRNAs in the Ovary of Polycystic Ovary Syndrome with Hyperandrogenism and Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    Lin Lin; Tao Du; Jia Huang; Li-Li Huang; Dong-Zi Yang

    2015-01-01

    Background:Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age.The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovulation and signs of hyperandrogenism.The cause and effect relationship of hyperinsulinemia and hyperandrogenemia (HA) is still debated.Micro-ribonucleic acids (miRNAs) have recently been shown to play a role in regulation of ovarian function.Our current study focused on the altered expression of miRNAs with PCOS.Methods:Ovarian theca intema tissues were obtained from 10 PCOS patients and 8 controls that were non-PCOS and had normal insulin sensitivity undergoing laparoscopy and/or ovarian wedge resection.Total RNA of all samples was extracted.We studied the repertoire of miRNAs in both PCOS and non-PCOS women by microarray hybridization.Bioinformatic analysis was performed for predicting targets of the differentially expressed miRNAs.Furthermore,selected miRNAs were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).Results:A total of 27 miRNAs were differentially expressed in PCOS patients with respect to the controls in our discovery evaluationand two (miR-92a and miR-92b) of them were significantly downregulated in PCOS women in followed validation (P < 0.05).Targets prediction revealed that miR-92a targeted both GATA family of zinc finger transcription factor GATA-binding factor 6 (GATA6) and insulin receptor substrate proteins 2 (IRS-2).Conclusions:MiRNAs are differentially expressed between PCOS patients and controls.We identified and validated two miRNAs-miR-92a and miR-92b.They are significantly downregulated and may be involved in the pathogenesis of PCOS.

  10. Neck circumference as a new anthropometric indicator for prediction of insulin resistance and components of metabolic syndrome in adolescents: Brazilian Metabolic Syndrome Study

    OpenAIRE

    Cleliani de Cassia da Silva; Mariana Porto Zambon; Vasques,Ana Carolina J.; Ana Maria de B. Rodrigues; Daniella Fernandes Camilo; Antonio, Maria Ângela R. G. M.; Cassani,Roberta Soares L.; Bruno Geloneze

    2014-01-01

    OBJECTIVE: To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents. METHODS: Cross-sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist cir...

  11. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.

    Science.gov (United States)

    Poelkens, Fleur; Lammers, Gerwen; Pardoel, Elisabeth M; Tack, Cees J; Hopman, Maria T E

    2013-10-01

    The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance.

  12. Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.

    Science.gov (United States)

    Morrison, John A; Glueck, Charles J; Umar, Muhammad; Daniels, Stephen; Dolan, Lawrence M; Wang, Ping

    2011-01-01

    The objective of the study was to evaluate preteen insulin and metabolic syndrome (MS) as independent predictors of impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) in black and white females by mean age of 24 years. This was a prospective cohort study. There were 8 measures of fasting glucose and insulin from mean age of 10 years through mean age of 24 years, and insulin also at mean age of 25 years. Childhood MS was defined by at least 3 abnormal values among waist circumference, triglyceride, high-density lipoprotein cholesterol, blood pressure, and glucose. Hyperinsulinemia was defined by insulin greater than or equal to race-specific 75th percentile. Patients with type 1 diabetes mellitus were excluded. The study was held in schools and in an outpatient clinical center. Participants were schoolgirls (260 white, 296 black). There was no intervention. The outcome measures were IFG (fasting glucose of at least 100 to 125 mg/dL) and T2DM (fasting glucose of at least 126 mg/dL). By the age of 24 years, there were 11 cases of T2DM (2%) and 108 cases of IFG (19%). By the age of 24 years, IFG + T2DM was present in 18% of women (73/412) who had normal insulin-no MS at the age of 10 years vs 28% (34/122) of those with high insulin-no MS at the age of 10 years (P = .014) and 67% (10/15) of those with high insulin + MS at the age of 10 years (P < .0001). By stepwise logistic regression, significant, independent, positive predictors of IFG + T2DM were first insulin measure in childhood, age at last sampling, childhood MS, change in body mass index over 15 years, and, separately, initial glucose of at least 100 mg/dL and average of all insulin quartile ranks over 15 years. The correlation between childhood insulin z score and insulin z score 15 years later was r = .30, P < .0001. Insulin and MS at a mean age of 10 years plus change in body mass index over 15 years, and 15-year average insulin rank independently predict IFG + T2DM by mean age of 24 years

  13. Effect of maternal lipid profile, C-peptide, insulin, and HBA1c levels during late pregnancy on large-for-gestational age newborns

    Institute of Scientific and Technical Information of China (English)

    Ruo-Lin Hou; Huan-Huan Zhou; Xiao-Yang Chen; Xiu-Min Wang; Jie Shao; Zheng-Yan Zhao

    2014-01-01

    Background: Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns. Methods: This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns. Results: Maternal TG, C-peptide, insulin and HbA1c levels were signifi cantly higher in the LGA group than in the AGA group (P Conclusion: High maternal TG level during late pregnancy is signifi cantly associated with LGA newborns.

  14. Waist circumference and insulin resistance: a community based cross sectional study on reproductive aged Iranian women

    Directory of Open Access Journals (Sweden)

    Zadeh-Vakili Azita

    2011-08-01

    Full Text Available Abstract Background Although the positive relationship between insulin resistance (IR and central obesity is well known, the direct relationship between waist circumference and IR is not clear yet and there is no consensus regarding the cut off value for waist circumference as a surrogate index for central obesity. The present study was aimed to determine the optimal cut-off value of waist circumference (WC for predicting IR in reproductive aged Iranian women. Methods Using the stratified, multistage probability cluster sampling method 1036 women were randomly selected from among reproductive aged women of different geographic regions of Iran. Following implementation of exclusion criteria, complete data for 907 women remained for analysis. Insulin resistance was evaluated by the homeostasis model assessment (HOMA-IR and its cut off value was defined as the 95th percentile of HOMA-IR value for 129 subjects, without any metabolic abnormality. The optimal cut-off of WC in relation to HOMA-IR was calculated based on the receiver operating characteristics (ROC curve analysis using the Youden index and the area under curve (AUC. Results The mean age of the total sample of 907 subjects was 34.4 ± 7.6 years (range, 18 - 45 years. After adjustment for age the odds ratios (OR of elevated HOMA-IR were progressively higher with increasing levels of waist circumference; the age adjusted OR of IR for women with WC > 95 cm in comparison to those subjects with WC Conclusions Waist circumference is directly related to insulin resistance and the optimal cut-off value for waist circumference reflecting insulin resistance is considered to be 88.5 cm for reproductive aged Iranian women.

  15. Neck circumference as a new anthropometric indicator for prediction of insulin resistance and components of metabolic syndrome in adolescents: Brazilian Metabolic Syndrome Study

    Directory of Open Access Journals (Sweden)

    Cleliani de Cassia da Silva

    2014-06-01

    Full Text Available OBJECTIVE: To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents.METHODS:Cross-sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist circumferences, and biochemical evaluation. The pubertal stage was obtained by self-assessment, and the blood pressure, by auscultation. Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin Resistance. The correlation between two variables was evaluated by partial correlation coefficient adjusted for the percentage of body fat and pubertal stage. The performance of neck circumference to identify insulin resistance was tested by Receiver Operating Characteristic Curve.RESULTS: After the adjustment for percentage body fat and pubertal stage, neck circumference correlated with waist circumference, blood pressure, triglycerides and markers of insulin resistance in both genders.CONCLUSIONS: The results showed that the neck circumference is a useful tool for the detection of insulin resistance and changes in the indicators of metabolic syndrome in adolescents. The easiness of application and low cost of this measure may allow its use in Public Health services.

  16. Could Metabolic Syndrome, Lipodystrophy, and Aging Be Mesenchymal Stem Cell Exhaustion Syndromes?

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    Eduardo Mansilla

    2011-01-01

    Full Text Available One of the most important and complex diseases of modern society is metabolic syndrome. This syndrome has not been completely understood, and therefore an effective treatment is not available yet. We propose a possible stem cell mechanism involved in the development of metabolic syndrome. This way of thinking lets us consider also other significant pathologies that could have similar etiopathogenic pathways, like lipodystrophic syndromes, progeria, and aging. All these clinical situations could be the consequence of a progressive and persistent stem cell exhaustion syndrome (SCES. The main outcome of this SCES would be an irreversible loss of the effective regenerative mesenchymal stem cells (MSCs pools. In this way, the normal repairing capacities of the organism could become inefficient. Our point of view could open the possibility for a new strategy of treatment in metabolic syndrome, lipodystrophic syndromes, progeria, and even aging: stem cell therapies.

  17. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression.

    Directory of Open Access Journals (Sweden)

    Tipwadee Bunprajun

    Full Text Available Both aging and physical inactivity are associated with increased development of insulin resistance whereas physical activity has been shown to promote increased insulin sensitivity. Here we investigated the effects of physical activity level on aging-associated insulin resistance in myotubes derived from human skeletal muscle satellite cells. Satellite cells were obtained from young (22 yrs normally active or middle-aged (56.6 yrs individuals who were either lifelong sedentary or lifelong active. Both middle-aged sedentary and middle-aged active myotubes had increased p21 and myosin heavy chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact on the metabolism of human myotubes during aging and may contribute to aging-associated insulin resistance through impaired GLUT4 localization.

  18. Relationship between Adiponectin Level, Insulin Sensitivity, and Metabolic Syndrome in Type 1 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Kristina Blaslov

    2013-01-01

    Full Text Available Objective. Adiponectin is known to be decreased in insulin resistance (IR and metabolic syndrome (MS which can be present in patients with type 1 diabetes mellitus (T1DM. The aim of this study was to evaluate the relationship between adiponectin level, MS, and insulin sensitivity in T1DM. Research Design and Methods. The study included 77 T1DM patients divided into two groups based on the total plasma adiponectin median value. Insulin sensitivity was calculated with the equation for eGDR, and MS was defined according to International Diabetes Federation criteria. Results. Patients with higher adiponectin level ( had significantly lower waist circumference (, fasting venous glucose levels (, higher HDL3-cholesterol (, and eGDR ( in comparison to the group with lower adiponectin who showed higher prevalence of MS (. eGDR increased for 1.09 mg/kg−1 min−1 by each increase of 1 µg/mL total fasting plasma adiponectin (. In the logistic regression model, adiponectin was inversely associated with the presence of MS (. Conclusion. Higher adiponectin concentration is associated with lower prevalence of MS in T1DM. Whether higher adiponectin concentration has a protective role in the development of the MS in T1DM needs to be clarified in future follow-up studies.

  19. Relationship between Adiponectin Level, Insulin Sensitivity, and Metabolic Syndrome in Type 1 Diabetic Patients

    Science.gov (United States)

    Blaslov, Kristina; Zibar, Karin; Duvnjak, Lea

    2013-01-01

    Objective. Adiponectin is known to be decreased in insulin resistance (IR) and metabolic syndrome (MS) which can be present in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between adiponectin level, MS, and insulin sensitivity in T1DM. Research Design and Methods. The study included 77 T1DM patients divided into two groups based on the total plasma adiponectin median value. Insulin sensitivity was calculated with the equation for eGDR, and MS was defined according to International Diabetes Federation criteria. Results. Patients with higher adiponectin level (n = 39) had significantly lower waist circumference (P < 0.002), fasting venous glucose levels (P < 0.001), higher HDL3-cholesterol (P = 0.011), and eGDR (P = 0.003) in comparison to the group with lower adiponectin who showed higher prevalence of MS (P = 0.045). eGDR increased for 1.09 mg/kg−1 min−1 by each increase of 1 µg/mL total fasting plasma adiponectin (P = 0.003). In the logistic regression model, adiponectin was inversely associated with the presence of MS (P = 0.014). Conclusion. Higher adiponectin concentration is associated with lower prevalence of MS in T1DM. Whether higher adiponectin concentration has a protective role in the development of the MS in T1DM needs to be clarified in future follow-up studies. PMID:23956744

  20. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    chain protein expression. Interestingly MHCIIa was increased only in myotubes from middle-aged active individuals. Middle-aged sedentary cells had intact insulin-stimulated Akt phosphorylation however, the same cell showed ablated insulin-stimulated glucose uptake and GLUT4 translocation to the plasma...... membrane. On the other hand, middle-aged active cells retained both insulin-stimulated increases in glucose uptake and GLUT4 translocation to the plasma membrane. Middle-aged active cells also had significantly higher mRNA expression of GLUT1 and GLUT4 compared to middle-aged sedentary cells......, and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...

  1. In skeletal muscle advanced glycation end products (AGEs) inhibit insulin action and induce the formation of multimolecular complexes including the receptor for AGEs.

    Science.gov (United States)

    Cassese, Angela; Esposito, Iolanda; Fiory, Francesca; Barbagallo, Alessia P M; Paturzo, Flora; Mirra, Paola; Ulianich, Luca; Giacco, Ferdinando; Iadicicco, Claudia; Lombardi, Angela; Oriente, Francesco; Van Obberghen, Emmanuel; Beguinot, Francesco; Formisano, Pietro; Miele, Claudia

    2008-12-26

    Chronic hyperglycemia promotes insulin resistance at least in part by increasing the formation of advanced glycation end products (AGEs). We have previously shown that in L6 myotubes human glycated albumin (HGA) induces insulin resistance by activating protein kinase Calpha (PKCalpha). Here we show that HGA-induced PKCalpha activation is mediated by Src. Coprecipitation experiments showed that Src interacts with both the receptor for AGE (RAGE) and PKCalpha in HGA-treated L6 cells. A direct interaction of PKCalpha with Src and insulin receptor substrate-1 (IRS-1) has also been detected. In addition, silencing of IRS-1 expression abolished HGA-induced RAGE-PKCalpha co-precipitation. AGEs were able to induce insulin resistance also in vivo, as insulin tolerance tests revealed a significant impairment of insulin sensitivity in C57/BL6 mice fed a high AGEs diet (HAD). In tibialis muscle of HAD-fed mice, insulin-induced glucose uptake and protein kinase B phosphorylation were reduced. This was paralleled by a 2.5-fold increase in PKCalpha activity. Similarly to in vitro observations, Src phosphorylation was increased in tibialis muscle of HAD-fed mice, and co-precipitation experiments showed that Src interacts with both RAGE and PKCalpha. These results indicate that AGEs impairment of insulin action in the muscle might be mediated by the formation of a multimolecular complex including RAGE/IRS-1/Src and PKCalpha.

  2. The utility of metformin therapy in reproductive-aged women with polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Nathan, Nisha; Sullivan, Shannon D

    2014-01-01

    Metformin, an insulin-sensitizing drug commonly used to treat Type 2 Diabetes Mellitus (T2DM), has been increasingly used off-label for the treatment of polycystic ovary syndrome (PCOS), which affects at least 5-10% of reproductive- age women. With very little risk associated with its use, metformin provides many important benefits to women with PCOS, including regulating menstrual cycles, improving clinical signs of hyperandrogenism, ameliorating metabolic syndrome, inducing ovulation, improving pregnancy rates and pregnancy outcomes, preventing gestational diabetes, and preventing progression to T2DM. Here, we review the indications for metformin in women with PCOS, with a focus on the use of metformin during pre-conception and pregnancy.

  3. The comparison of the intestinal adaptation effects of subcutaneous and oral insulin in a rats with short bowel syndrome

    Directory of Open Access Journals (Sweden)

    Unal Bicakci

    2013-01-01

    Full Text Available Aim: Insulin has been reported to have positive effects on intestinal adaptation after short bowel syndrome when applicated oral or subcutaneously. The purpose of this study is to compare the intestinal adaptation effects of subcutaneous and oral routes of insulin in rats with short bowel syndrome. Materials and Methods: The short bowel syndrome (SBS was performed through 70-75% of small intestinal resection and an end-to-end anastomosis. The control group rats underwent SBS only. In the second group, oral insulin (1 U/ml was administrated twice-daily. In the last group, the insulin was administrated subcutaneously (1 U/kg as in the control group. All rats were killed on day 15. Outcome parameters were weight of small intestine, the crypt length, villous depth, the blood levels of vascular endothelial growth factor (VEGF, and granolocyt-monocyst colony-stimulating factor (GMCSF. Results: Intestinal weight was significantly more in oral insulin group and subcutaneous insulin group than in the control group (72.6 ± 4.3, 78.6 ± 4.8 and 59.7 ± 4.8 (P 0.05. VEGF values were not statistically significant between the groups (200.3 ± 41.6, 178.9 ± 30.7 and 184.3 ± 52.2 (P > 0.05. GMCSF was statistically higher in the control group than in other groups (3.34 ± 1.34, 1.56 ± 0.44 and 1.56 ± 0.44 (P < 0.05. Conclusion: Insulin has positive effects on intestinal adaptation in short bowel syndrome. Subcutaneous administration is slightly more effective than the oral route.

  4. Down syndrome and aging: a leadership and social justice landscape.

    Science.gov (United States)

    Nevel, Kathleen M

    2010-01-01

    The growing phenomenon of aging adults with Down syndrome and other intellectual and developmental disabilities and dementia can be traumatic and overwhelming for families and caregivers. The realization is beset with angst and necessitates restructuring policies and programs while exploring the leadership landscape to facilitate a values framework for persons with Down syndrome. This article considers the changing role of the caregiver and the influences of community support networks, social policy, social justice, and quality of life adaptations for aging persons with Down syndrome and dementia. Note: To maintain confidentiality, personal communications noted throughout this article identify the individual using initials rather than surname.

  5. Aging-related correlation of insulin-degrading enzyme with gamma-secretase-generated products involving insulin and glucose levels in transgenic mice.

    Science.gov (United States)

    Hwang, Dae Y; Cho, Jung S; Kim, Chuel K; Shim, Sun B; Jee, Seung W; Lee, Su H; Seo, Su J; Cho, Joon Y; Lee, Seok H; Kim, Yong K

    2005-09-01

    Insulin-degrading enzyme (IDE) is a 110-kDa thiol zinc-methalloendopeptidase that can cleave small Abeta peptides and the APP intracellular domain (AICD). The aim of this study was to examine aging-related correlation of IDE with gamma-secretase-generated products involving insulin and glucose levels in transgenic brains expressing neuron-specific enolase (NSE)-controlled human mutant presenilin-2 (hPS2m). Herein, we concluded that the levels of IDE expression in transgenic brains were decreased relative to those of control mice at 15 months of age. In parallel, inhibition in the IDE expression at this age underlies to the levels-up of Abeta-42, AICD, gamma-secretase, and glucose with a level-down of insulin. Thus, IDE expression is critical target for the therapeutic trials.

  6. Effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in children with metabolic syndrome: a triple-masked controlled trial

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2014-01-01

    Full Text Available OBJECTIVE: this triple-masked controlled trial aimed to assess the effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in obese children and adolescents. METHODS: the study comprised 50 participants, aged 10 to16 years, who were randomly assigned into two groups of equal number. In this 12-week trial, one group received oral vitamin D (300,000 IU and the other group received placebo. Cardiometabolic risk factors, insulin resistance, and a continuous value of metabolic syndrome (cMetS were determined. Statistical analysis was conducted after adjustment for covariate interactions. RESULTS: overall, 21 patients in the vitamin D group and 22 in the placebo group completed the trial. No significant difference was observed in the baseline characteristics of the two groups. After the trial, in the vitamin D group, serum insulin and triglyceride concentrations, as well as HOM -IR and C-MetS decreased significantly, both when compared with the baseline and with the placebo group. No significant difference was observed when comparing total cholesterol, LDL-C, HDL-C, fasting blood glucose, and blood pressure. CONCLUSION: the present findings support the favorable effects of vitamin D supplementation on reducing insulin resistance and cardiometabolic risk factors in obese children.

  7. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Højlund, Kurt; Glintborg, Dorte; Andersen, Nicoline Resen

    2008-01-01

    OBJECTIVE: Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo...... in muscle of PCOS patients. Akt phosphorylation at Ser473 and Thr308 correlated positively with R(d) and NOGD in the insulin-stimulated state. Serum free testosterone was inversely related to insulin-stimulated R(d) and NOGD in PCOS. Importantly, the pioglitazone-mediated improvement in insulin....... CONCLUSIONS: Impaired insulin signaling through Akt and AS160 in part explains insulin resistance at the molecular level in skeletal muscle in PCOS, and the ability of pioglitazone to enhance insulin sensitivity involves improved signaling through Akt and AS160. Moreover, our data provide correlative evidence...

  8. Jiawei Erzhiwan improves menopausal metabolic syndrome by enhancing insulin secretion in pancreatic β cells.

    Science.gov (United States)

    Wan, Xiao-Meng; Zhang, Mu; Zhang, Pei; Xie, Zhi-Shen; Xu, Feng-Guo; Zhou, Ping; Ma, Shi-Ping; Xu, Xiao-Jun

    2016-11-01

    Menopausal metabolic syndrome (MMS) is a series of syndrome caused by ovarian function decline and hormone insufficiency, and is a high risk factor for cardiovascular diseases (CVD) and type II diabetes mellitus (T2DM). Erzhiwan (EZW), composed of Herba Ecliptae and Fructus Ligustri Lucidi, is a traditional Chinese herbal formula that has been used to treat menopausal syndrome for many years. We added Herba Epimedii, Radix Rehmanniae, and Fructus Corni into EZW, to prepare a new formula, termed Jiawei Erzhiwan (JE). The present study was designed to determine the anti-MMS effects of JE using ovariectomized (OVX) adult female rats that were treated with JE for 4 weeks, and β-tc-6 cells and INS cells were used to detected the protect effectiveness of JE. Our results showed JE could increase insulin sensitivity and ameliorated hyperlipidemia. Metabolomics analysis showed that the serum levels of branched and aromatic amino acids were down-regulated in serum by JE administration. Moreover, JE enhanced the function of islet β cells INS-1 and β-tc-6, through increasing the glucose stimulated insulin secretion (GSIS), which was abolished by estrogen receptor (ER) antagonist, indicating that JE functions were mediated by ER signaling. Additionally, JE did not induce tumorigenesis in rat mammary tissue or promoted proliferation of MCF-7 and Hela cells. In conclusion, our work demonstrated that JE ameliorated OVX-induced glucose and lipid metabolism disorder through activating estrogen receptor pathway and promoting GSIS in islet β cells, thus indicating that JE could be a safe and effective medication for MMS therapy.

  9. The Metabolic Syndrome in Diabetic Hispanic Adults and the Role of Secondary Actos Treatment in Insulin Sensitivity Based on Gender

    Directory of Open Access Journals (Sweden)

    Gustavo E. Villarreal

    2009-12-01

    Full Text Available Background: The prevalence of the metabolic syndrome in diabetics is highest among Hispanic adults. A thiazolidinedione antidiabetic agent found in Actos contributes to its mechanism of action. Actos also decreases insulin resistance in margin of the liver, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. This study primarily focuses on the effects of the secondary treatment of Actos on a group of South Texas Hispanics at risk for Type II diabetes; the participants’ ages ranged from 22 to 86 years. These results were based on their metabolic syndrome health data and the extent of recovery on the basis of their gender. Multiple regression analyses have been conducted to determine the factors affecting the metabolic syndrome data on the gender after secondary treatment. Some auxiliary analyses pertaining to cholesterol levels and weight vs. gender comparisons have been carried out to show the gender disparity.Aims and Objectives: The purpose of this study was to establish the prevalence of the metabolic syndrome in the South Texas region and of individual variables which contributed to obesity of Hispanics at risk for Type II diabetes. Patients with the metabolic syndrome have three or more of these risk factors that include excessive abdominal fat, hypertension, low amounts of HDL cholesterol, elevated triacylglyceride levels, and abnormal blood sugar. They are also three-and-a-half times as likely to die from risks associated with coronary heart disease, as well as an increased risk of liver and kidney disease, and possibly cancer. Non-drug treatment programs for metabolic syndrome such as weight loss, dietary changes, and increased physical activity, decreased the incidence of metabolic syndrome by almost 41 percent, whereas the incidence rate among these patients on drug therapy was reduced by only 17 percent to conclude that there are other options available.Methods and Experimental Design: A

  10. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome

    NARCIS (Netherlands)

    Poelkens, F.; Lammers, G.; Pardoel, E.M.; Tack, C.J.J.; Hopman, M.T.E.

    2013-01-01

    The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms r

  11. Association of adiponectin,free fatty acids,and insulin resistance with metabolic syndrome and its components in Uygur Xinjiang

    Institute of Scientific and Technical Information of China (English)

    闫贻忠

    2014-01-01

    Objective To investigate the association of adiponectin(APN),free fatty acids(FFA),and insulin resistance(IR)with metabolic syndrome(MS)and its components.Methods In the baseline survey,the subjects were divided into MS group and the control group based

  12. Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

    Science.gov (United States)

    Schnackenberg, Christine G; Costell, Melissa H; Krosky, Daniel J; Cui, Jianqi; Wu, Charlene W; Hong, Victor S; Harpel, Mark R; Willette, Robert N; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  13. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Christine G. Schnackenberg

    2013-01-01

    Full Text Available Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1. Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp, cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d, a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  14. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria

    2004-01-01

    a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate...

  15. Syndrome of insulin resistance with acanthosis nigricans, acral hypertrophy and muscle cramps in an adolescent - a rare diagnosis revisited.

    Science.gov (United States)

    Ghosh, Urmi; Thomas, Maya; Mathai, Sarah

    2014-12-01

    The authors report a 14-y-old boy with insulin resistance, acanthosis nigricans, acral hypertrophy and muscle cramps. While there was a dramatic response of the muscle cramps to phenytoin therapy, some other features of metabolic syndrome did not respond to phenytoin therapy alone.

  16. Serum insulin-like growth factor 1 in the aging horse

    DEFF Research Database (Denmark)

    Lygren, Tone; Hansen, Sanni; Langberg, Henning

    2014-01-01

    BACKGROUND: Insulin-like growth factor 1 (IGF-1) has important roles in anabolic processes in the musculoskeletal system and has been reported to decrease with age in both people and horses. OBJECTIVES: The objective of this study was to determine serum IGF-1 levels in the aging horse from early...... to late adulthood (age range 5-27 years). METHODS: Healthy horses (n = 72) were used in a cross-sectional study, while 37 paired serum samples were available for a longitudinal study. Serum IGF-1 protein was determined using an ELISA kit validated for use in equine samples. RESULTS: No association...... was found between serum IGF-1 levels and age in the cross-sectional study. In the longitudinal study, a latent variable model fitted to the data revealed that horses in general experienced a 5.2% increase of serum IGF-1 levels over a 5-year period, but horses crossing a change point around 9 years of age...

  17. [Genetic iron overloads and hepatic insulin-resistance iron overload syndrome: an update].

    Science.gov (United States)

    Ruivard, M

    2009-01-01

    Hepcidin inhibits intestinal absorption of iron through internalisation of ferroportin. Its discovery helps to better understand the genetic iron overloads. The insulin resistance-hepatic iron overload (IR-HIO)--also coined as the dysmetabolic iron overload syndrome--is a common cause or iron overload. This article is a review about genetic iron overloads and IR-HIO. Type 1 haemochromatosis C282Y +/+ accounts for 95% of the haemochromatosis. Hepatic fibrosis may develop if serum ferritin is higher than 1000 microg/l but can be partially reversible with phlebotomies. Juvenile haemochromatosis (type 2) and type 3 haemochromatosis (mutation of the transferrin receptor 2) are very uncommon. Several mutations of the ferroportin gene can cause usually mild iron overload of autosomal dominant inheritance. Aceruleoplasminemia is an uncommon disorder involving cerebral iron overload. The causes and consequences of the IR-HIO are unknown. Treatment of IR-HIO is focused on metabolic syndrome and phlebotomies are questionable because the overload is moderate and intestinal absorption of iron seems to be low. MRI (or other non invasive methods) is needed to truly assess iron overload because serum ferritin overestimates it in metabolic syndrome. Several points have to be elucidated: how HFE interferes with hepcidin in type 1 haemochromatosis; the causes of variability of iron overload; the benefits of populations screening; the advantage of phlebotomies in IR-HIO; the use of new oral iron chelators.

  18. Changes in androgens and insulin sensitivity indexes throughout pregnancy in women with polycystic ovary syndrome (PCOS: relationships with adverse outcomes

    Directory of Open Access Journals (Sweden)

    Falbo Angela

    2010-10-01

    Full Text Available Abstract Background Given the high rate of pregnancy and perinatal complications recently observed in patients with polycystic ovary syndrome (PCOS and the lack of data on the serum variations in androgens and insulin sensitivity indexes in pregnant women with PCOS, the current study was aimed to assess these changes and their potential effect on pregnancy outcomes in a population of women with PCOS. Methods Forty-five pregnant patients with ovulatory PCOS (PCOS group and other 42 healthy pregnant women (control group were studied assaying serum androgen levels and insulin sensitivity indexes throughout pregnancy serially, and recording obstetrical outcomes. Results Serum androgen levels and insulin resistance indexes were significantly (p p p Conclusions PCOS patients have impaired changes in serum androgen levels and insulin sensitivity indexes during pregnancy. These alterations could be implicated in the pregnancy and neonatal complications frequently observed in women affected by PCOS.

  19. [ROLE OF NEUTRAL SPHINGOMYELINASE IN AGE-DEPENDENT MUSCLE INSULIN RESISTANCE DEVELOPMENT AND ITS IMPROVEMENT WITH N-ACETYLCYSTEINE].

    Science.gov (United States)

    Babenko, N A; Timofiĭchuk, O A; Belyĭ, A N

    2015-01-01

    In the present study, we evaluated the role of ceramide in age-dependent and etoposide-induced insulin resistance. A significant increase in the level of ceramide and decrease of gluthatione (GSH) content and tissue sensitivity to insulin has been observed in 24-month-old rats as compared with 3-month-old animals. Etoposide imitates ageing-like changes in muscle tissue of young rats. N-acetylcysteine as well as specific neutral sphingomyelinase (nSMase) inhibitor--GW4869, decreases ceramide content and increases GSH level, and enhances the insulin-induced [3H-D-glucose uptake in the "aged" tissue. These data indicate that nSMase play important role in the age- and drug-induced ceramide-dependent insuline resistance.

  20. Beneficial effect of melatonin treatment on age-related insulin resistance and on the development of type 2 diabetes.

    Science.gov (United States)

    Tresguerres, Jesus A F; Cuesta, Sara; Kireev, Roman A; Garcia, Cruz; Acuña-Castroviejo, Dario; Vara, Elena

    2013-12-01

    Abstract This paper will review the effect of aging on glucose metabolism and insulin resistance in pancreas and in peripheral tissues and how melatonin administration could affect these parameters. In SAMP8 mice insulin levels in plasma were found to be increased together with enhanced HOMA-IR values, whereas insulin content in pancreas showed a decrease with aging. Aging in SAMP8 mice was also associated with a significant increase in the relative expression of both protein and mRNA of different pro-inflammatory mediators. Furthermore, aging was associated with a decrease in the expression of Pdx-1, FoxO 1 and FoxO 3A and Sirt 1 in pancreas SAMP8 samples. Melatonin administration was able to reduce these age-related alterations, decreasing plasma insulin levels and increasing its pancreatic content in SAMP8 mice. HOMA-IR was decreased with melatonin treatment in all animals. Conversely, in SAMP8 mice, melatonin treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin. Furthermore it was also able to increase the expression of Sirt 1, Pdx-1 and FoxO 3A. The present study has shown that aging is associated with significant alterations in the relative expression of pancreatic genes involved in both insulin secretion and glucose metabolism and that these are associated with an increase in inflammation and oxidative stress. Melatonin administration was able to reduce oxidative stress and inflammation and thus to improve pancreatic function in old mice. By doing so, insulin resistance is diminished and plasma insulin is reduced, enhancing insulin pancreatic content and reducing plasma glucose levels and HOMA index.

  1. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels.

    Science.gov (United States)

    Rasmussen, D D; Boldt, B M; Wilkinson, C W; Yellon, S M; Matsumoto, A M

    1999-02-01

    Human and rat pineal melatonin secretion decline with aging, whereas visceral fat and plasma insulin levels increase. Melatonin modulates fat metabolism in some mammalian species, so these aging-associated melatonin, fat and insulin changes could be functionally related. Accordingly, we investigated the effects of daily melatonin supplementation to male Sprague-Dawley rats, starting at middle age (10 months) and continuing into old age (22 months). Melatonin was added to the drinking water (92% of which was consumed at night) at a dosage (4 microg/ml) previously reported to attenuate the aging-associated decrease in survival rate in male rats, as well as at a 10-fold lower dosage. The higher dosage produced nocturnal plasma melatonin levels in middle-aged rats which were 15-fold higher than in young (4 months) rats; nocturnal plasma melatonin levels in middle-aged rats receiving the lower dosage were not significantly different from young or middle-aged controls. Relative (% of body wt) retroperitoneal and epididymal fat, as well as plasma insulin and leptin levels, were all significantly increased at middle age when compared to young rats. All were restored within 10 weeks to youthful (4 month) levels in response to both dosages of melatonin. Continued treatment until old age maintained suppression of visceral (retroperitoneal + epididymal) fat levels. Plasma corticosterone and total thyroxine (T4) levels were not significantly altered by aging or melatonin treatment. Plasma testosterone, insulin-like growth factor I (IGF-I) and total triiodothyronine (T3) decreased by middle age; these aging-associated decreases were not significantly altered by melatonin treatment. Thus, visceral fat, insulin and leptin responses to melatonin administration may be independent of marked changes in gonadal, thyroid, adrenal or somatotropin regulation. Since increased visceral fat is associated with increased insulin resistance, diabetes, and cardiovascular disease, these results

  2. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer.

    Science.gov (United States)

    Anisimov, Vladimir N; Bartke, Andrzej

    2013-09-01

    Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor-1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients.

  3. The key role of growth hormone — insulin — IGF-1 signaling in aging and cancer

    Science.gov (United States)

    Anisimov, Vladimir N.; Bartke, Andrzej

    2014-01-01

    Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors in aging. GH/Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes increases lifespan in nematodes, fruit flies and mice. The life-prolonging effects of caloric restriction are likely related to decreasing IGF-1 levels. Evidence has emerged that antidiabetic drugs are promising candidates for both lifespan extension and prevention of cancer. Thus, antidiabetic drugs postpone spontaneous carcinogenesis in mice and rats, as well as chemical and radiation carcinogenesis in mice, rats and hamsters. Furthermore, metformin seems to decrease the risk for cancer in diabetic patients. PMID:23434537

  4. Down Syndrome and the aging process: a systematic review

    OpenAIRE

    Bruno de Sousa Lopes; Lucy Gomes Vianna; Clayton Franco Moraes; Gustavo de Azevedo Carvalho; Vicente Paulo Alves

    2015-01-01

    The study aimed to identify and update the knowledge about older people with Down Syndrome (DS), and to understand the peculiarities of the aging process in this population. Bibliographical research conducted by Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and High Wire portal. Inclusion criteria were articles published in the last ten years with the words “Down Syndrome" and “Elderly”.  

  5. Bivariate linkage analysis of the insulin resistance syndrome phenotypes on chromosome 7q.

    Science.gov (United States)

    Lehman, Donna M; Arya, Rector; Blangero, John; Almasy, Laura; Puppala, Sobha; Dyer, Thomas D; Leach, Robin J; O'Connell, Peter; Stern, Michael P; Duggirala, Ravindranath

    2005-04-01

    Metabolic abnormalities of the insulin resistance syndrome (IRS) have been shown to aggregate in families and to exhibit trait-pair correlations, suggesting a common genetic component. A broad region on chromosome 7q has been implicated in several studies to contain loci that cosegregate with IRS-related traits. However, it is not clear whether such loci have any common genetic (pleiotropic) influences on the correlated traits. Also, it is not clear whether the chromosomal regions contain more than one locus influencing the IRS-related phenotypes. In this study we present evidence for linkage of five IRS-related traits [body mass index (BMI), waist circumference (WC), In split proinsulin (LSPI), In triglycerides (LTG), and high-density lipoprotein cholesterol (HDLC)] to a region at 7q11.23. Subsequently, to gain further insight into the genetic component(s) mapping to this region, we explored whether linkage of these traits is due to pleiotropic effects using a bivariate linkage analytical technique, which has been shown to localize susceptibility regions with precision. Four hundred forty individuals from 27 Mexican American families living in Texas were genotyped for 19 highly polymorphic markers on chromosome 7. Multipoint variance component linkage analysis was used to identify genetic location(s) influencing IRS-related traits of obesity (BMI and WC), dyslipidemia (LTG and HDLC), and insulin levels (LSPI); the analysis identified a broad chromosomal region spanning approximately 24 cM. To gain more precision in localization, we used a bivariate linkage approach for each trait pair. These analyses suggest localization of most of these bivariate traits to an approximately 6-cM region near marker D7S653 [7q11.23, 103-109 cM; a maximum bivariate LOD of 4.51 was found for the trait pair HDLC and LSPI (the LODeq score is 3.94)]. We observed evidence of pleiotropic effects in this region on obesity and insulin-related trait pairs.

  6. Genetic polymorphisms associated with steroids metabolism and insulin action in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Ramos Cirilo, Priscila Daniele; Rosa, Fabíola Encinas; Moreira Ferraz, Maria Fernanda

    2012-01-01

    Polycystic ovary syndrome (PCOS) is an endocrinopathy associated with infertility, diabetes and cardiovascular events. This study aimed to correlate polymorphisms of genes involved in the biosynthesis and metabolism of steroids and insulin action (CYP17A1, CYP19A1, AR, ESR1, ESR2, INSR, IGF2...... [CA](n) genes were evaluated by PCR-based GeneScan analysis, while CYP17A1 5'UTR (rs743572), INSR 1058 CT (rs1799817), and IGF2 3'UTR GA (rs680) polymorphisms were evaluated by PCR-RFLP. The results showed a prevalence of PAI1 4G5G+4G4G genotypes in PCOS (p = 0.025). Younger PCOS women showed...

  7. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine W; Rasmussen, Susanne

    2007-01-01

    OBJECTIVES: The goal was to clarify if insulin resistance (IR) would predict cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn). BACKGROUND: Although the cause of MetSyn is not well defined, IR has been proposed to be an important cause. Only a small number of population......, smoking, and low-density lipoprotein cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to 2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The corresponding figures for NCEP...

  8. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Agarwalla Vipin

    2007-02-01

    Full Text Available Abstract Background The rising prevalence of obesity and metabolic syndrome (MetS has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS and severe obesity as predictors of insulin resistance (IR in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290. Sensitivity, specificity, positive predictive values and odds ratios (OR with 95% confidence intervals (CI were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006. Sensitivities were Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for IR should be routinely performed. Further research is needed to establish threshold values of insulin measures in overweight children who may be at greater associated risk of adverse outcomes whether or not MetS is present.

  9. The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2010-05-01

    To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery.

  10. Insulin-like growth factor I, growth hormone, and insulin sensitivity: the effects of a one-year cholecalciferol supplementation in middle-aged overweight and obese subjects.

    Science.gov (United States)

    Kamycheva, Elena; Berg, Vivian; Jorde, Rolf

    2013-04-01

    Both altered GH-IGF-I axis and low serum levels of 25-hydroxyvitamin D (25(OH)D) are linked to measures of metabolic syndrome. Our hypothesis was that there is a relation between GH, IGF-I, and 25(OH)D; and that vitamin D supplementation may have an effect on the levels of GH, IGF-I, and IGF-I/IGFBP-3 ratio. 318 overweight and obese subjects completed a one-year randomized intervention with either 40,000 or 20,000 IU cholecalciferol per week or placebo. GH, IGF-I, IGFBP-3 and measures of insulin resistance were evaluated at baseline and at the end of study. There was a significant relation between entities of GH-IGF-I axis and insulin resistance. Subjects with severe obesity had significantly lower serum 25(OH)D and had a significant linear decline in IGF-I/IGFBP-3 ratio with increasing serum 25(OH)D quartiles. Vitamin D status was an independent predictor of GH-IGF-I axis and supplementation with vitamin D decreased IGF-I/IGFBP-3 ratio in subjects without severe obesity. No corresponding effect of vitamin D supplementation on BMI or insulin resistance was observed. Adverse effects of GH-IGF-I axis on glucose metabolism and the development of metabolic syndrome may be in part associated with the changes in vitamin D status.

  11. Lowered insulin signalling ameliorates age-related sleep fragmentation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Athanasios Metaxakis

    2014-04-01

    Full Text Available Sleep fragmentation, particularly reduced and interrupted night sleep, impairs the quality of life of older people. Strikingly similar declines in sleep quality are seen during ageing in laboratory animals, including the fruit fly Drosophila. We investigated whether reduced activity of the nutrient- and stress-sensing insulin/insulin-like growth factor (IIS/TOR signalling network, which ameliorates ageing in diverse organisms, could rescue the sleep fragmentation of ageing Drosophila. Lowered IIS/TOR network activity improved sleep quality, with increased night sleep and day activity and reduced sleep fragmentation. Reduced TOR activity, even when started for the first time late in life, improved sleep quality. The effects of reduced IIS/TOR network activity on day and night phenotypes were mediated through distinct mechanisms: Day activity was induced by adipokinetic hormone, dFOXO, and enhanced octopaminergic signalling. In contrast, night sleep duration and consolidation were dependent on reduced S6K and dopaminergic signalling. Our findings highlight the importance of different IIS/TOR components as potential therapeutic targets for pharmacological treatment of age-related sleep fragmentation in humans.

  12. Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-Aged Mice to Diet-Induced Insulin Resistance

    NARCIS (Netherlands)

    Koonen, Debby P. Y.; Sung, Miranda M. Y.; Kao, Cindy K. C.; Dolinsky, Vernon W.; Koves, Timothy R.; Ilkayeva, Olga; Jacobs, Rene L.; Vance, Dennis E.; Light, Peter E.; Muoio, Deborah M.; Febbraio, Maria; Dyck, Jason R. B.

    2010-01-01

    OBJECTIVE-Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal m

  13. Risk factors for Type 2 Diabetes Mellitus : Metabolic Syndrome, Insulin Resistance and Primary Prevention

    OpenAIRE

    Hydrie, Muhammad Zafar Iqbal

    2012-01-01

    Aims: The purpose of the study was to identify the extent of metabolic syndrome on the basis of ATP III and IDF definition in subjects aged 25 years and above from an urban population of Karachi. Also to see the association of risk factors related to diabetes and metabolic syndrome in this population. And finally to prove the hypothesis of intervention effect on the onset of type 2 diabetes in a high risk urban population and evaluate the rate of conversion of IGT to diabetes by these interve...

  14. Effect of Rosiglitazone on Endocrine, Metabolism and Ovulatory Performance in Patients with Polycystic Ovary Syndrome and Insulin Resistance

    Institute of Scientific and Technical Information of China (English)

    吕立群; 刘义

    2004-01-01

    The effect of rosiglitazone on endocrine, metabolism and ovulatory performance in the paitents with polycystic ovary syndrome(PCOS) and insulin resistance was investigated. Twentyfive patients diagnosed as having polycystic ovary syndrome (PCOS) combined with insulin resistance were treated with rosiglitazone for 12 weeks. Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone (T), androstenedione (A), sex hormone binding globulin (SHBG), insulin and glucose concentration, total cholesterol, triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholestero (LDL-C), apolipoprotein A, apolipoprotein B levels and ovulatory performance were determined. The results showed that after treatment serum insulin levels was decreased significantly (P<0.01). The HDL-C was increased while LDL-C decreased significantly (P<0.05, P<0.01). The serum LH, T, A concentrations and the ratio of LH/FSH were decreased, while SHBG levels increased significantly (P<0.01). The ovulation rate during clomiphene citrate therapy was 72 %, significantly higher than that before treatment. It is likely that reduction of hyperinsulinemia that is produce by rosiglitazone may effectively improve the endocrine, metabolism and ovulatory performance in the patients with PCOS and insulin resistance.

  15. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8).

    Science.gov (United States)

    Cuesta, Sara; Kireev, Roman; García, Cruz; Rancan, Lisa; Vara, Elena; Tresguerres, Jesús A F

    2013-06-01

    The aim of the present study was to investigate the effect of aging on several parameters related to glucose homeostasis and insulin resistance in pancreas and how melatonin administration could affect these parameters. Pancreas samples were obtained from two types of male mice models: senescence-accelerated prone (SAMP8) and senescence-accelerated-resistant mice (SAMR1). Insulin levels in plasma were increased with aging in both SAMP8 and SAMR1 mice, whereas insulin content in pancreas was decreased with aging in SAMP8 and increased in SAMR1 mice. Expressions of glucagon and GLUT2 messenger RNAs (mRNAs) were increased with aging in SAMP8 mice, and no differences were observed in somatostatin and insulin mRNA expressions. Furthermore, aging decreased also the expressions of Pdx-1, FoxO 1, FoxO 3A and Sirt1 in pancreatic SAMP8 samples. Pdx-1 was decreased in SAMR1 mice, but no differences were observed in the rest of parameters on these mice strains. Treatment with melatonin was able to decrease plasma insulin levels and to increase its pancreatic content in SAMP8 mice. In SAMR1, insulin pancreatic content and plasma levels were decreased. HOMA-IR was decreased with melatonin treatment in both strains of animals. On the other hand, in SAMP8 mice, treatment decreased the expression of glucagon, GLUT2, somatostatin and insulin mRNA. Furthermore, it was also able to increase the expression of Sirt1, Pdx-1 and FoxO 3A. According to these results, aging is associated with significant alterations in the relative expression of pancreatic genes associated to glucose metabolism. This has been especially observed in SAMP8 mice. Melatonin administration was able to improve pancreatic function in old SAMP8 mice and to reduce HOMA-IR improving their insulin physiology and glucose metabolism.

  16. [Role of the growth hormone-insulin-like growth factor-1-insulin system signaling in aging and longevity: evolutional aspect].

    Science.gov (United States)

    Anisimov, V N

    2008-09-01

    Growth hormone (GH)/ insulin-like growth factor 1 (IGF-1)/ insulin signaling molecules linked to longevity include DAF-2 and insulin-receptor and their homologues in mammals, and to inactivation of corresponding genes followed by increased life span in nematodes, fruit flies, and mice. It is possible that the life-prolonging effect of calorie restriction is due to decreasing IGF-1 levels. A search of pharmacological modulators of life-span-extending mutations in the GH/IGF-1/insulin signaling pathway and mimetic effects of caloric restriction is a priority directions in the regulation of longevity. Some literature and our own observations suggest that antidiabetic drugs could be promising candidates for both life span extension and prevention of cancer.

  17. Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history.

    Directory of Open Access Journals (Sweden)

    Dongyu Wang

    Full Text Available BACKGROUND: Fibroblast growth factor 19 (FGF19 and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM and explored their relationships with anthropometric and endocrine parameters. METHOD: Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA in patients with GDM (n = 30 and healthy pregnant controls (n = 60 matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters. RESULTS: Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history. CONCLUSIONS: Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.

  18. Leptin, insulin and thyroid hormones in a cohort of Egyptian obese Down syndrome children: a comparative study

    Directory of Open Access Journals (Sweden)

    Yahia Sohier

    2012-10-01

    Full Text Available Abstract Background Obesity is a major worldwide health problem. It is commonly observed in Down syndrome individuals than in the general population. The reason for increased risk of obesity in DS is unclear. The current study was designed to clarify differences in some obesity- related hormones in a group of prepubertal Down syndrome children. Methods Thirty six Egyptian children with Down syndrome were enrolled in this study, divided according to their body mass index (BMI into 23 obese and13 non obese. Another group of 43 non Down children were recruited, they were divided according to their BMI into 20 patients having simple obesity and 23 non obese, as control groups. Fasting blood samples were collected for estimation of fasting blood glucose (FBG, insulin, leptin, free thyroxin (FT4, thyroid stimulating hormones (TSH and creatine kinase (CK. Insulin resistance was assessed by Homeostasis Model Assessment method (HOMA-IR. The ratio of leptin to BMI (LEP/BMI was used as an index of leptin resistance. Results Median values of FBG, insulin, and HOMA-IR were significantly higher in Down versus non Down groups, while median values of leptin and leptin resistance were non-significantly different among Down versus non Down groups. Median TSH values were non- significantly different between obese Down and obese non Down. Although the median values of TSH and FT4 were within normal range in Down groups, four cases of subclinical hypothyroidism were encountered. Leptin levels were correlated with insulin and IR but not with TSH in Down groups. Conclusion Increased circulating leptin, a marker of leptin resistance in obese children with Down syndrome seems to be similar to that in children with simple obesity. Elevated FBG and insulin in obese Down children highlights the presence of early IR. Associated myopathy evidenced by mildly elevated CK levels could be an added factor for obesity in such group of patients.

  19. Differential Development of Inflammation and Insulin Resistance in Different Adipose Tissue Depots Along Aging in Wistar Rats: Effects of Caloric Restriction.

    Science.gov (United States)

    Sierra Rojas, Johanna X; García-San Frutos, Miriam; Horrillo, Daniel; Lauzurica, Nuria; Oliveros, Eva; Carrascosa, Jose María; Fernández-Agulló, Teresa; Ros, Manuel

    2016-03-01

    The prevalence of insulin resistance and type 2 diabetes increases with aging and these disorders are associated with inflammation. Insulin resistance and inflammation do not develop at the same time in all tissues. Adipose tissue is one of the tissues where inflammation and insulin resistance are established earlier during aging. Nevertheless, the existence of different fat depots states the possibility of differential roles for these depots in the development of age-associated inflammation and insulin resistance. To explore this, we analyzed insulin signaling and inflammation in epididymal, perirenal, subcutaneous, and brown adipose tissues during aging in Wistar rats. Although all tissues showed signs of inflammation and insulin resistance with aging, epididymal fat was the first to develop signs of inflammation and insulin resistance along aging among white fat tissues. Subcutaneous adipose tissue presented the lowest degree of inflammation and insulin resistance that developed latter with age. Brown adipose tissue also presented latter insulin resistance and inflammation but with lower signs of macrophage infiltration. Caloric restriction ameliorated insulin resistance and inflammation in all tissues, being more effective in subcutaneous and brown adipose tissues. These data demonstrate differential susceptibility of the different adipose depots to the development of age-associated insulin resistance and inflammation.

  20. The insulin autoimmune syndrome (IAS) as a cause of hypoglycaemia: an update on the pathophysiology, biochemical investigations and diagnosis.

    Science.gov (United States)

    Ismail, Adel A A

    2016-11-01

    Insulin autoimmune syndrome (IAS) is considered to be very rare in Caucasians. Understanding its pathophysiology is paramount in (a) appreciating its potential impact on analyses of pancreatic hormones and (b) explaining its highly variable clinical manifestations in non-diabetic, non-acutely ill patients with indeterminate hypoglycaemia. The underlying aetiology of IAS is the presence of variable affinity/avidity endogenous insulin antibodies in significant amounts. The two types of insulin antibodies namely antibodies which bind insulin and/or proinsulin(s) and receptor antibodies (insulin mimetic) will be discussed. Their biochemical and immunological roles in causing hypoglycaemia will be highlighted. Clinical manifestations of IAS can vary from mild and transient to spontaneous, severe and protracted hypoglycaemia necessitating in extreme cases plasmapheresis for glycaemic control. Antibodies of IAS can interfere in pancreatic immunoassay tests causing erroneous and potentially misleading results. Thorough testing for endogenous insulin antibodies must be considered in the investigations of non-diabetic, non-acutely ill patients with indeterminate and/or unexplained hypoglycaemia.

  1. [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

    Science.gov (United States)

    Halmos, Tamás; Suba, Ilona

    2016-01-03

    The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean

  2. Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study

    Science.gov (United States)

    Schuur, M.; Henneman, P.; van Swieten, J. C.; Zillikens, M. C.; de Koning, I.; Janssens, A. C. J. W.; Witteman, J. C. M.; Aulchenko, Y. S.; Frants, R. R.; Oostra, B. A.; van Dijk, K. Willems

    2010-01-01

    While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women. PMID:20585974

  3. Prevalence, incidence, and age at diagnosis in Marfan Syndrome

    DEFF Research Database (Denmark)

    Groth, Kristian A; Hove, Hanne; Kyhl, Kasper;

    2015-01-01

    Background: Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria...... have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome. Method: Using unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977......-2014). Following, we confirmed or rejected the diagnosis according to the 2010 revised Ghent nosology. Results: We identified a total of 1628 persons with possible Marfan syndrome. We confirmed the diagnosis in 412, whereof 46 were deceased, yielding a maximum prevalence of 6.5/100,000 at the end of 2014...

  4. Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging

    Science.gov (United States)

    Wrigley, Sarah; Arafa, Donia; Tropea, Daniela

    2017-01-01

    Insulin-like growth factor 1 (IGF1) is a polypeptide hormone structurally similar to insulin. It is central to the somatotropic axis, acting downstream of growth hormone (GH). It activates both the mitogen-activated protein (MAP) kinase and PI3K signaling pathways, acting in almost every tissue in the body to promote tissue growth and maturation through upregulation of anabolic processes. Overall GH and IGF1 signaling falls with age, suggesting that it is this reduced IGF1 activity that leads to age-related changes in organisms. However, mutations that reduce IGF1-signaling activity can dramatically extend the lifespan of organisms. Therefore, the role of IGF1 in the overall aging process is unclear. This review article will focus on the role of IGF1 in brain development and aging. The evidence points towards a role for IGF1 in neurodevelopment both prenatally and in the early post-natal period, and in plasticity and remodeling throughout life. This review article will then discuss the hallmarks of aging and cognitive decline associated with falls in IGF1 levels towards the end of life. Finally, the role of IGF1 will be discussed within the context of both neuropsychiatric disorders caused by impaired development of the nervous system, and neurodegenerative disorders associated with aging. IGF1 and its derivatives are shown to improve the symptoms of certain neuropsychiatric disorders caused by deranged neurodevelopment and these effects have been correlated with changes in the underlying biology in both in vitro and in vivo studies. On the other hand, studies looking at IGF1 in neurodegenerative diseases have been conflicting, supporting both a role for increased and decreased IGF1 signaling in the underlying pathogenesis of these diseases. PMID:28203146

  5. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    Energy Technology Data Exchange (ETDEWEB)

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  6. Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

    Science.gov (United States)

    Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy; Awara, Mahmoud A; Moniz, Caje; le Roux, Carel W

    2011-09-01

    Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.

  7. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome

    OpenAIRE

    Schmitz Gerd; John Swen; Melnik Bodo C

    2011-01-01

    Abstract The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulat...

  8. Association of Microalbuminuria with Metabolic Syndrome among Aged Population.

    Science.gov (United States)

    Li, Xiao-Hong; Lin, Hai-Yan; Wang, Shu-Hua; Guan, Li-Ying; Wang, Yi-Bing

    2016-01-01

    Background. The impact of the various components of metabolic syndrome (MetS) on chronic kidney disease has been conflicting. We aim to investigate the association between MetS and microalbuminuria and identify the major contributing components of MetS that result in microalbuminuria in the Chinese aged population. Methods. A total of 674 adults aged 55-98 years (males: 266; mean age: 66.5 ± 7.5 years) were studied. MetS was defined by the 2004 Chinese Diabetes Society criteria and microalbuminuria by urine albumin-creatinine ratio (UACR) ≥3 mg/mmoL. Results. The prevalence of microalbuminuria was gradually increased with increasing number of MetS components (P microalbuminuria (OR = 1.781, 95% CI = 1.226-2.587; P microalbuminuria in the Chinese aged population. Elevated FPG is the most predominant component of metabolic syndrome associated with microalbuminuria followed by elevated SBP and reduced HDL-C.

  9. Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

    Science.gov (United States)

    Michaud, Kathy; Forget, Helene; Cohen, Henri

    2009-01-01

    Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

  10. The phenotype of polycystic ovary syndrome ameliorates with aging

    NARCIS (Netherlands)

    Brown, Zoe A.; Louwers, Yvonne V.; Fong, Sharon Lie; Valkenburg, Olivier; Birnie, Erwin; de Jong, Frank H.; Fauser, Bart C. J. M.; Laven, Joop S. E.

    2011-01-01

    Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Design: Retrospective longitudinal follow-up study. Setting: Tertiary care center. Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on c

  11. Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.

    Directory of Open Access Journals (Sweden)

    Christelle Bertrand

    Full Text Available Thyroid hormones (TH play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3 receptor (p43 which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43-/- mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43-/- mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.

  12. Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin

    DEFF Research Database (Denmark)

    Svendsen, Pernille Fog; Nilas, Lisbeth; Madsbad, Sten;

    2009-01-01

    . Polycystic ovary syndrome (PCOS) is associated with insulin resistance, and the pathophysiologic mechanisms behind PCOS resemble those of type 2 diabetes mellitus; therefore, women with PCOS may have alterations in the incretin hormone response. Metformin is widely used in the treatment of both type 2......In normal subjects, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 70% of the insulin response during a meal; but in diabetic subjects and other insulin-resistant conditions, the incretin effect is impaired...... diabetes mellitus and PCOS. Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect. The objective of the study was to measure incretin hormone secretion in women with PCOS and to evaluate the effect of metformin...

  13. Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-treated patients with growth hormone deficiency or Laron syndrome.

    Science.gov (United States)

    Brat, O; Ziv, I; Klinger, B; Avraham, M; Laron, Z

    1997-01-01

    Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and quadriceps) were measured by a computerized device in three groups: (A) 4 boys with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24 months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I) treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome. For each patient, 2 matched controls, by age, sex, physical activity and height below the 50th percentile, were examined. GH- or IGF-I-deficient patients before treatment revealed reduced muscle force and endurance. GH treatment (0.6 U/kg/week) restored muscle force and endurance, progressively, mainly in the boys with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in patients with Laron syndrome proved to have a weaker effect than GH in restoring muscle force. The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones.

  14. Influence of advanced age of maternal grandmothers on Down syndrome

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    Ramachandra Nallur B

    2006-01-01

    Full Text Available Abstract Background Down syndrome (DS is the most common chromosomal anomaly associated with mental retardation. This is due to the occurrence of free trisomy 21 (92–95%, mosaic trisomy 21 (2–4% and translocation (3–4%. Advanced maternal age is a well documented risk factor for maternal meiotic nondisjunction. In India three children with DS are born every hour and more DS children are given birth to by young age mothers than by advanced age mothers. Therefore, detailed analysis of the families with DS is needed to find out other possible causative factors for nondisjunction. Methods We investigated 69 families of cytogenetically confirmed DS children and constructed pedigrees of these families. We also studied 200 randomly selected families belonging to different religions as controls. Statistical analysis was carried out using logistic regression. Results Out of the 69 DS cases studied, 67 were free trisomy 21, two cases were mosaic trisomy 21 and there were none with translocation. The number of DS births was greater for the young age mothers compared with the advanced age mothers. It has also been recorded that young age mothers (18 to 29 years born to their mothers at the age 30 years and above produced as high as 91.3% of children with DS. The logistic regression of case- control study of DS children revealed that the odds ratio of age of grandmother was significant when all the four variables were used once at a time. However, the effect of age of mother and father was smaller than the effect of age of maternal grandmother. Therefore, for every year of advancement of age of the maternal grandmother, the risk (odds of birth of DS baby increases by 30%. Conclusion Besides the known risk factors, mother's age, father's age, the age of the maternal grandmother at the time of birth of the mother is a risk factor for the occurrence of Down syndrome.

  15. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    Science.gov (United States)

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury.

  16. Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

    Directory of Open Access Journals (Sweden)

    Amanda L Kauffman

    2010-05-01

    Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

  17. Growth hormone, insulin-like growth factor-1 and the aging brain.

    Science.gov (United States)

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.

  18. Progress on Insulin Resistance Syndrome%胰岛素抵抗综合征的研究近况

    Institute of Scientific and Technical Information of China (English)

    徐焱成

    2004-01-01

    胰岛素抵抗综合征(insulin resistance syndrome,IRS),又称为X综合征或代谢综合征(metabolic syndrome,MS)。目前的国际疾病分类编号为ICD-9277.7,名为代谢异常综合征(dysmetabolic syndrome)。

  19. Hyperandrogenism-insulin resistance-acanthosis nigricans syndrome with PCOS and Hashimoto's thyroiditis: case report

    Directory of Open Access Journals (Sweden)

    Amarnath Kulkarni

    2015-09-01

    Full Text Available Female hyperandrogenism is a frequent motive of consultation. It is revealed by hirsutism, acne or seborrhea, and disorders in menstruation cycle combined or not with virilisation signs. Several etiologies are incriminated but the hyperandrogenism-insulin resistance-acanthosis nigricans syndrome is rare. A 21-year female, having had a three-year-old secondary amenorrhea, known case of hypothyroidism since 4 years on medication. The exam revealed a patient, hypertensive with blood pressure at 170/110 mmHg with a Body Mass Index (BMI at 40.08 (Obese Class-3, as per WHO 2004 and a waist measurement of 106cm, a severe hirsutism assessed to be 27 according to Ferriman and Gallwey scale, acanthosis nigricans behind the neck and elbows. The assessment carried out revealed testosteronemia at 1.07 ng/mL, which is more than twice the upper normal of the laboratory. Imaging studies revealed enlarged right adrenal gland, hepatomegaly with fatty infiltration of grade-1 also bilateral polycystic ovaries. The retained diagnosis is HAIR-AN syndrome with polycystic ovaries, hypertension, type-II diabetes mellitus, hypothyroidism since last 4-years and dyslipidemia and was provided with metformin 500 mg thrice daily, spironolactone 25 mg twice daily, atorvastatin 20 mg once daily, telmisartan 20 mg once daily with continuation of eltroxin 50 Mcg for hypothyroidism. To our knowledge this is the first case report of HAIR-AN syndrome in 21 year old female associated with Hashimoto's thyroiditis, dyslipidaemia, hypertension and type-2-diabetes and this case also highlights about early diagnosis and management of HAIR-AN Syndrome with PCOS and Hashimoto's thyroiditis which could help prevent long-term sequalae such as cardiovascular disease and endometrial cancer and with the advent of knowledge and availability of health resources we can prevent long-term adverse effects (threefold on health of women. This woman should be observed for these ailments in later life

  20. The changes of insulin secretion in type A insulin resistance syndrome: a 7-year follow up%A型胰岛素抵抗综合征胰岛素分泌变化的七年随访

    Institute of Scientific and Technical Information of China (English)

    黄知敏; 李延兵; 陈蔼玲; 万学思; 姚斌; 肖海鹏

    2011-01-01

    Objective A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. Methods Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3rd, 6th and 7th year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years.Acute insulin response (AIR) was determined at baseline and the 7th year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. Results The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbAlc) being normal (4.6%-5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4-5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. Conclusions It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and β-cell secretion does not deteriorate over time as glucose homeostasis maintains.%目的 对1例A型胰岛素抵抗综合征患者随访7年,观察血糖及胰岛素分泌变化.方法 患者初诊年龄16岁,分别于基线、第3、6、7年进行临床随访,观察患者延长口服葡萄糖耐量试验(OGTT)及同步胰岛素、C肽的分泌,比较各随访年血糖、胰岛素、C肽曲线下面积(AUC);比较基线与第7年静脉葡萄糖耐量试验急性胰岛素分泌反应(AIR)的变化;将延长OGTT各时间点胰岛素分泌速

  1. Aging in Persons with Rett Syndrome: An Updated Review

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    Meir Lotan

    2010-01-01

    Full Text Available Rett syndrome (RS is a neurological disease affecting mainly females, characterized by an arrest of brain development caused by an X-linked mutation. Rett syndrome is the first human disease found to be caused by defects in a protein involved in regulating gene expression through its interaction with methylated DNA. The disease has been traced to a defective gene called MECP2. The case stories presented here and recent findings show that females with RS are able to live into old age. Due to the observed longevity of individuals with RS, and the fact that individuals with RS present the therapist/physician with specific clinical challenges, it is suggested that proper, long-term, and individually tailored, intensive care should be provided at all ages in the hope to prevent or at least reduce the age-related deterioration that is typical of this population.

  2. Down Syndrome and the aging process: a systematic review

    Directory of Open Access Journals (Sweden)

    Bruno Sousa Lopes

    2015-05-01

    Full Text Available The study aimed to identify and update the knowledge about older people with Down Syndrome (DS, and to understand the peculiarities of the aging process in this population. Bibliographical research conducted by Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and High Wire portal. Inclusion criteria were articles published in the last ten years with the words “Down Syndrome" and “Elderly”.  

  3. Down Syndrome and the aging process: a systematic review

    OpenAIRE

    Lopes, Bruno Sousa; Universidade Católica de Brasília (UCB). Brasília (DF).; Vianna, Lucy Gomes; Universidade Católica de Brasília (UCB); Moraes, Clayton Franco; Universidade Católica de Brasília (UCB).; Carvalho, Gustavo de Azevedo; Universidade Católica de Brasília (UCB). Brasília (DF).; Alves, Vicente Paulo; Universidade Católica de Brasília (UCB). Brasília (DF).

    2015-01-01

    The study aimed to identify and update the knowledge about older people with Down Syndrome (DS), and to understand the peculiarities of the aging process in this population. Bibliographical research conducted by Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and High Wire portal. Inclusion criteria were articles published in the last ten years with the words “Down Syndrome" and “Elderly”.   O estudo teve como objetivo identificar e atualizar os conheci...

  4. AGE AND GENDER MAY INFLUENCE THE RESULTS OF ROUX-EN-Y GASTRIC BYPASS? Metabolic syndrome parameters

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    Stephan Garcia ANDRADE-SILVA

    2014-09-01

    Full Text Available Context Severe obesity affects the body favoring the development of serious diseases, including hypertension, diabetes mellitus, atherosclerosis and non alcoholic fatty liver disease. Bariatric procedures increased in Brazil in the last decade. Objectives The purpose of this study was to verify if gender and age in date of procedure resulted significant differences in metabolic syndrome parameters after surgery. Methods The study involved 205 medical records of adult patients undergoing Roux-en-Y gastric bypass, stratified by gender and age groups and followed one year by a multidisciplinary team. Results It was observed significant decrease in body mass index, fasting glucose and insulin at all ages and both genders. Lipid profile showed significant improvements except high density lipoprotein cholesterol. Ectopic fat in the liver has decreased after 6 months in patients classified with steatosis at baseline. Patients classified as hypertensive blood pressure levels decreased 6 months after surgical intervention. Conclusions Roux-en-Y gastric bypass proved to be an important tool in remission of metabolic syndrome parameters. The reduction of body mass accompanied to decrease in insulin resistance resulted in lower prevalence of comorbidities associated with obesity. The benefits were similar and extended both genders and all age groups between 18 and 65 years old.

  5. Lipid Profile In Relation To Anthropometric Indices and Insulin Resistance in Overweight Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Maryam Saghafi-Asl

    2013-12-01

    Full Text Available Background: The present study was aimed to investigate lipid profile in relation to anthropometric indices and insulin resistance in overweight or obese women with polycystic ovary syndrome (PCOS. Methods: In this cross-sectional study, lipid profile and anthropometric indices including body mass index (BMI, waist and hip circumference, waist to hip ratio (WHR, and waist to height ratio (WHtR were evaluated in 63 over-weight or obese PCOS patients subdivided into insulin-resistant (IR and non-insulin-resistant (NIR groups. IR was defined as homeostasis model of insulin resistance (HOMA-IR ≥3.8. Results: Fasting insulin concentration and HOMA-IR were higher (P<0.001 and high-density lipoprotein cholesterol (P=0.012 was lower in IR group. All of the anthropometric measures other than WHR and BMI showed significant correlations with several lipid parameters. Amongst, WHtR showed the strongest correlation with total cholesterol (TC (r=0.37; P=0.004 and low-density lipoprotein cholesterol (LDL-C (r=0.33; P=0.011 in the whole PCOS patients. Conclusion: Anthropometric characteristics (especially BMI and hip circumference are more important parameters correlated to lipid profile than IR in overweight or obese PCOS patients, confirming the importance of early treatment of obesity to prevent dyslipidemia in the future.

  6. Dietary magnesium intake improves insulin resistance among non-diabetic individuals with metabolic syndrome participating in a dietary trial.

    Science.gov (United States)

    Wang, Jinsong; Persuitte, Gioia; Olendzki, Barbara C; Wedick, Nicole M; Zhang, Zhiying; Merriam, Philip A; Fang, Hua; Carmody, James; Olendzki, Gin-Fei; Ma, Yunsheng

    2013-09-27

    Many cross-sectional studies show an inverse association between dietary magnesium and insulin resistance, but few longitudinal studies examine the ability to meet the Recommended Dietary Allowance (RDA) for magnesium intake through food and its effect on insulin resistance among participants with metabolic syndrome (MetS). The dietary intervention study examined this question in 234 individuals with MetS. Magnesium intake was assessed using 24-h dietary recalls at baseline, 6, and 12 months. Fasting glucose and insulin levels were collected at each time point; and insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). The relation between magnesium intake and HOMA-IR was assessed using linear mixed models adjusted for covariates. Baseline magnesium intake was 287 ± 93 mg/day (mean ± standard deviation), and HOMA-IR, fasting glucose and fasting insulin were 3.7 ± 3.5, 99 ± 13 mg/dL, and 15 ± 13 μU/mL, respectively. At baseline, 6-, and 12-months, 23.5%, 30.4%, and 27.7% met the RDA for magnesium. After multivariate adjustment, magnesium intake was inversely associated with metabolic biomarkers of insulin resistance (P 3.6) over time was 71% lower [odds ratio (OR): 0.29; 95% confidence interval (CI): 0.12, 0.72] in participants in the highest quartile of magnesium intake than those in the lowest quartile. For individuals meeting the RDA for magnesium, the multivariate-adjusted OR for high HOMA-IR over time was 0.37 (95% CI: 0.18, 0.77). These findings indicate that dietary magnesium intake is inadequate among non-diabetic individuals with MetS and suggest that increasing dietary magnesium to meet the RDA has a protective effect on insulin resistance.

  7. Cinnamon improves insulin sensitivity and alters body composition in an animal model of the metabolic syndrome

    Science.gov (United States)

    Polyphenols from cinnamon (CN) have been described recently as insulin sensitizers and antioxidants, but their effects on the glucose/insulin system in vivo have not been totally investigated. The aim of this study was to determine the effects of CN on insulin resistance and body composition, using ...

  8. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

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    Sara Hägg

    Full Text Available BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s to determine the average biological age of carotid plaques. METHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14C content by accelerator mass spectrometry. The average plaque age (i.e. formation time was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014. Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5. However, plaques in the lowest tercile of plaque age (most recently formed were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively, less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05, and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05 than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results show, for the first time, that plaque age, as judge by relative incorporation of (14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.

  9. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Buhl, Esben Selmer; Jessen, Niels; Pold, Rasmus

    2002-01-01

    clamp conditions. To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia......The insulin resistance syndrome is characterized by several risk factors for cardiovascular disease. Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action......, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic...

  10. Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance: a randomized trial of normoglycemic women with midlife weight gain.

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    Harriette R Mogul

    Full Text Available RATIONALE: Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion. OBJECTIVE: To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D, and in combination with metformin (M and metformin plus low-dose rosiglitazone (MR, in diverse women with midlife weight gain (defined as >20lbs since the twenties, normal glucose tolerance, and hyperinsulinemia. PARTICIPANTS: 46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers. METHODS: A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization. MAIN OUTCOME MEASURE: Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS measures, leptin, and adiponectin. RESULTS: Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032. HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013. Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001 Study medications were well tolerated. CONCLUSIONS: These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that

  11. Impact of the Xba1-polymorphism of the human muscle glycogen synthase gene on parameters of the insulin resistance syndrome in a Danish twin population

    DEFF Research Database (Denmark)

    Fenger, M; Poulsen, P; Beck-Nielsen, H;

    2000-01-01

    was increased in female carriers of the A2-allele with impaired glucose tolerance or Type 2 diabetes mellitus (79 +/- 1 vs. 94 +/- 4 mmHg, P insulin resistance syndrome were associated with the polymorphism. CONCLUSIONS......AIMS: To establish the impact on the insulin resistance syndrome of the intron 14 Xba1-polymorphism in human muscle glycogen synthase (GYS1). METHODS: Parameters related to the insulin resistance syndrome were measured in 244 monozygotic twins and 322 dizygotic twins with or without impaired...... and the remainder had the genotype A1A2. No A2A2-genotypes were detected. In 11 genotypic discordant dizygotic twin pairs the insulin resistance was significantly increased in the twins carrying the A1A2 genotype regardless of sex (HOMA index 1.81 (A1A1) vs. 2.57 (A1A2), P

  12. Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling.

    Science.gov (United States)

    Yin, Fei; Jiang, Tianyi; Cadenas, Enrique

    2013-02-01

    Mitochondria generate second messengers, such as H2O2, that are involved in the redox regulation of cell signalling and their function is regulated by several cytosolic signalling pathways. IIS [insulin/IGF1 (insulin-like growth factor 1) signalling] in the brain proceeds mainly through the PI3K (phosphatidylinositol 3-kinase)-Akt (protein kinase B) pathway, which is involved in the regulation of synaptic plasticity and neuronal survival via the maintenance of the bioenergetic and metabolic capacities of mitochondria. Conversely, the JNK (c-Jun N-terminal kinase) pathway is induced by increased oxidative stress and JNK translocation to the mitochondrion results in impairment of energy metabolism. Moreover, IIS and JNK signalling interact with and antagonize each other. This review focuses on functional outcomes of a metabolic triad that entails the co-ordination of mitochondrial function (energy transducing and redox regulation), IIS and JNK signalling, in the aging brain and in neurodegenerative disorders, such as Alzheimer's disease.

  13. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

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    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  14. Molecular ageing in progeroid syndromes: Hutchinson-Gilford progeria syndrome as a model

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    da Nóbrega Raphael

    2009-04-01

    Full Text Available Abstract Hutchinson-Gilford progeria syndrome (HGPS is a rare premature aging disorder that belongs to a group of conditions called laminopathies which affect nuclear lamins. Mutations in two genes, LMNA and ZMPSTE24, have been found in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported mutation. The aim of this work was to compile a comprehensive literature review of the clinical features and genetic mutations and mechanisms of this syndrome as a contribution to health care workers. This review shows the necessity of a more detailed clinical identification of Hutchinson-Gilford progeria syndrome and the need for more studies on the pharmacologic and pharmacogenomic approach to this syndrome.

  15. Effect of insulin-like growth factor-I treatment on serum androgens and testicular and penile size in males with Laron syndrome (primary growth hormone resistance).

    Science.gov (United States)

    Laron, Z; Klinger, B

    1998-02-01

    Serum gonadotrophins. androgens, insulin and insulin-like growth factor-I (IGF-I) were determined before and during long-term treatment with recombinant IGF-I of seven males with Laron syndrome, and the changes correlated with changes in testicular volume and penile size. The subjects were four boys below the age of 5, two boys aged 10 and 14 but prepubertal and one 28-year-old fully sexually developed adult. IGF-I was administered by a once daily subcutaneous injection of 150 microg/kg per day to the boys and 120 microg/kg per day to the adult patient. In the very young boys no change in serum gonadotrophins, androgens, gonads or genitals was registered. In the two older boys and the adult patient, there was a progressive rise in luteinizing hormone, follicle-stimulating hormone and testosterone. Concomitantly, there was an increase in size of the testes and penile length. The two boys started puberty. As very high serum IGF-I levels were registered in the adult patient, the daily dose was progressively decreased to 70 microg/kg per day. Stopping the IGF-I administration in this patient, according to the protocol, led to a return to pretreatment serum levels and testicular and penile size. This report shows for the first time a direct effect of IGF-I on sex hormones and sex organs in the male.

  16. Insulin resistant diabetes mellitus without the presence of insulin antibodies. A case report.

    Science.gov (United States)

    Páv, J; Srámková, J; Matys, Z

    1976-07-01

    A case of a 26-year old woman suffering from an insulin resistant diabetes mellitus for 14 years is described. Acanthosis nigricans was diagnosed in the patient's second year and the syndrome of Stein-Leventhal at the age of 15. Diabetes could not be properly controlled either with the daily dosis of insulin as high as 1140 U or with peroral tolbutamide. Fasting serum IRI concentrations were elevated, the secretoric response to the stimulation by glucose or tolbutamide was substantial and protracted. The hypoglycemic response to the i.v. application of commercial insulin was insignificant. Serum growth hormone levels were normal. No presence of insulin antibodies in the serum was detected.

  17. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; van Buchem, Mark A;

    2015-01-01

    [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR...

  18. A simple way to identify insulin resistance in non-diabetic acute coronary syndrome patients with impaired fasting glucose

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    Sayantan Ray

    2012-01-01

    Full Text Available Background and Objective: The incidence of coronary artery disease (CAD is increasing in India. Recent data suggesting insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity, or dyslipidemia, so a focus on the relation between acute coronary syndrome (ACS and insulin resistance is relevant. Several studies addressing serum lipoprotein ratios as surrogates for insulin resistance have found promising results. We analyzed the association of lipoprotein ratios with the homeostatic model assessment of insulin resistance (HOMA-IR. Methods: One hundred non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. Admission fasting glucose and insulin concentrations were measured. The HOMA-IR was used to calculate insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG, and high-density lipoprotein (HDL-C levels are used to calculate following lipid ratios: TC/HDL-C and TG/HDL-C. The areas under the curves (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum lipoprotein ratio markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA Index >2 as compared to patients with Index <2. TG/HDL-C ratio and TC/HDL-C ratio were significantly correlated with HOMA-IR (P < 0.05 as obtained by Pearson′s correlation analysis (r = 0.4459, P = 0.0012; r = 0.4815, P = 0.0004; r = 0.3993; P = 0.0041, respectively. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratios for predicting insulin resistance was 0.80 (95% CI, 0.67-0.93, 0.78 (95% CI, 0.65-0.91, respectively. Conclusion: A plasma TG/HDL-C ratio and TC/HDL-C ratio provide a simple means of identifying insulin resistant and can be used as the markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  19. Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

    Science.gov (United States)

    Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

    2015-06-01

    The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

  20. Genetics and aging; the Werner syndrome as a segmental progeroid syndrome.

    Science.gov (United States)

    Martin, G M

    1985-01-01

    The maximum lifespan potential is a constitutional feature of speciation and must be subject to polygenic controls acting both in the domain of development and in the domain of the maintenance of macromolecular integrity. The enormous genetic heterogeneity that characterizes our own species, the complexities of numerous nature-nurture interactions, and the quantitative and qualitative variations of the senescent phenotype that are observed suggest that precise patterns of aging in each of us may be unique. Patterns of aging may also differ sharply among species (for example, semelparous vs. multiparous mammals). Some potential common denominators, however, allow one to identify progeroid syndromes in man that could lead to the elucidation of important pathways of gene action. (The suffix "-oid" means "like"; it does not mean identity.) Unimodal progeroid syndromes (eg., familial dementia of the Alzheimer type, an autosomal dominant) can help us understand the pathogenesis of a particular aspect of the senescent phenotype of man. Segmental progeroid syndromes (eg. the Werner syndrome, an autosomal recessive) may be relevant to multiple aspects of the senescent phenotype. Some results of research on the Werner syndrome may be interpreted as support for "peripheral" as opposed to "central" theories of aging; they are consistent with the view that gene action in the domain of development (adolescence, in this instance) can set the stage for patterns of aging in the adult; they point to the importance of mesenchymal cell populations in the pathogenesis of age-related disorders; finally, they underscore the role of chromosomal instability, especially in the pathogenesis of neoplasia.

  1. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  2. ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria.

    Science.gov (United States)

    Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Kirwan, Breda; O'Dea, Angela; Glynn, Liam G; McGuire, Brian E; O'Shea, Paula M; Dunne, Fidelma P

    2015-02-01

    Women with previous gestational diabetes (GDM) are a high-risk group for future development of diabetes, metabolic syndrome, and cardiovascular disease. The new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria significantly increase the number of women diagnosed with GDM. The long-term metabolic outcome in these women is unknown. We set out to determine the prevalence of metabolic syndrome, using adult treatment panel-III criteria; and insulin resistance, using HOMA2-IR, in white European women with previous GDM. Using a cohort design, we invited women meeting IADPSG GDM criteria across four Irish antenatal centres between 2007 and 2010 to participate. Two hundred and sixty-five women with previous values meeting IADPSG criteria for GDM participated (44 % of the population eligible for participation). Mean age was 36.7 years (SD 5.0). These women were compared with a randomly selected control group of 378 women (mean age 37.6 years, SD 5.1) known to have normal glucose tolerance (NGT) in pregnancy during the same period. A total of 25.3 % of women with previous IADPSG-defined GDM met metabolic syndrome criteria, compared to 6.6 % of women with NGT [at 2.6 (SD 1.0) vs. 3.3 years (SD 0.7) post-partum]. The prevalence of HOMA2-IR >1.8 was higher in women with previous IADPSG-defined GDM (33.6 vs. 9.1 % with NGT, p Women with previous GDM by IADPSG criteria demonstrate a greater than threefold prevalence of metabolic syndrome compared to women with NGT in pregnancy. Efforts to prevent projected long-term consequences of this should focus on interventions both in the preconception and post-partum periods.

  3. Study of Mutation in Tyrosine Protein Kinase of Insulin Receptor Gene in Patients with Polycystic Ovarian Syndrome

    Institute of Scientific and Technical Information of China (English)

    Min LI; Hong-yu QIU; Yong-yu SUN; Hong-fa LI; Yong-li CHU

    2003-01-01

    Objective To explore the molecular mechanism of insulin resistance in the patients with polycystic ovarian syndrome (PCOS)Methods Polymerase chain reaction, silver staining-single strand conformation polymorphism(PCR-SSCP) and DNA direct sequencing were used to detect the mutation of insulin receptor(INSR) gene in exon 17~21 with the abdominal wall adipose tissue from 31 patients with PCOS (PCOS Group) and 30 patients with pure hysteromyoma in reproductive lift (Control Group).Results Twenty-two variant SSCP patterns in exon 17 of INSR gene were detected. Direct sequence analysis of exon 17 showed that homozygous nonsense mutation was two alleles single nucleotide polymorphism(SNP) at the codon 1058 (CAC→CAT). Exons 18~21 were not detected with any significantly mutation. The INSR gene His1058C→T substitution collecting rate and insulin resistance were significantly higher in the PCOS group than in the control group (P=0.0293, P<0.05, P<0.01).Conclusion It is suggested that the SNP in codon 1058 of the INSR gene might be related with the insulin resistance in PCOS patients, which has hereditary tendency. And the missense mutation,nonsense mutation and frameshift mutation at exons 18~21 in tyrosine protein kinase region of INSR gene for PCOS patients were not frequently observed.

  4. Inositol's and other nutraceuticals' synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives.

    Science.gov (United States)

    Paul, Cristiana; Laganà, Antonio Simone; Maniglio, Paolo; Triolo, Onofrio; Brady, David M

    2016-06-01

    The incidence of metabolic syndrome (MetS), type II diabetes (T2D) and polycystic ovarian syndrome (PCOS) has been progressively increasing. Insulin resistance (InsR) seems to play a key role in a majority of phenotypes of these conditions, altering metabolic homeostasis, within muscle, liver, adipose and other tissues. Hyperinsulinemia is often associated with InsR and causes hormonal imbalances especially within ovaries and adrenals. Inositol is a polyalcohol, naturally occurring as nine stereoisomers, including D-chiro-inositol (DCI) and myo-inositol (MI), which have prominent roles in the metabolism of glucose and free fatty acids. MI and DCI have been classified as insulin-sensitizers and seem to adequately counteract several InsR-related metabolic alterations with a safe nutraceutical profile. Based on our analysis of selected studies that investigated MI and/or DCI, we conclude that supplementation with MI and/or DCI complement each other in their metabolic actions and act in synergy with other insulin sensitizing drugs and/or nutraceuticals. Nevertheless, considering the possible severe bias due to different methodologies across published studies, we conclude that there is a need for further studies on larger cohorts and with greater statistical power. These should further clarify outcomes and suitable therapeutic dosages of MI and DCI, possibly based on each patient's clinical status.

  5. Polycystic ovary syndrome and metabolic syndrome: the worrisome twosome?

    Science.gov (United States)

    Shah, D; Rasool, S

    2016-01-01

    By virtue of insulin resistance being the common etiology for polycystic ovary syndrome (PCOS) and metabolic syndrome, the cardiometabolic risks of these two syndromes are shared. The usual concerns of a PCOS patient are cosmetic or reproductive. However, there are more serious concerns past the reproductive age. Early treatment of insulin resistance, hypertension and hyperlipidemia reduces the long-term risk. This review highlights the unhealthy association of metabolic syndrome with PCOS and emphasizes the importance of early diagnosis, patient education and long-term follow-up beyond the reproductive age into menopause to prevent the long-term serious co-morbidities.

  6. Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: progress and controversies.

    Science.gov (United States)

    Sonntag, William E; Csiszar, Anna; deCabo, Raphael; Ferrucci, Luigi; Ungvari, Zoltan

    2012-06-01

    Because the initial reports demonstrating that circulating growth hormone and insulin-like growth factor-1 decrease with age in laboratory animals and humans, there have been numerous studies related to the importance of these hormones for healthy aging. Nevertheless, the role of these potent anabolic hormones in the genesis of the aging phenotype remains controversial. In this chapter, we review the studies demonstrating the beneficial and deleterious effects of growth hormone and insulin-like growth factor-1 deficiency and explore their effects on specific tissues and pathology as well as their potentially unique effects early during development. Based on this review, we conclude that the perceived contradictory roles of growth hormone and insulin-like growth factor-1 in the genesis of the aging phenotype should not be interpreted as a controversy on whether growth hormone or insulin-like growth factor-1 increases or decreases life span but rather as an opportunity to explore the complex roles of these hormones during specific stages of the life span.

  7. Late-Onset Hypogonadism in Male Patients Over 60 Years of Age with Metabolic Syndrome

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    Ekrem Kara

    2013-06-01

    Full Text Available Purpose: The aim of the study was to determine serum androgen levels and the frequency of late-onset hypogonadism (LOH in patients over 60 years of age with metabolic syndrome (MS and its correlation with parameters of MS. Material and Method: Men over 60 years of age who were diagnosed with MS according to the Adult Treatment Panel III (ATP III criteria in the internal medicine outpatient clinics at Cerrahpasa Medical School (n=30 and healthy controls (n=30 were included in the study. Total testosterone and sex hormone binding globulin (SHBG levels were analysed. Bioavailable and free testosterone levels were calculated. The participants filled up the Beck Depression Inventory (BDI and Aging Male Symptoms (AMS questionnaire forms themselves without any help of the physician. Results: LOH rates were 30% and 13.3% in the MS group and healthy control group, respectively (p=0.11. Serum total testosterone and SHBG levels were significantly lower in the MS group compared to controls (p=0.004 and p=0.003, respectively. A negative correlation was found between total testosterone and MS components. BDI and AMS questionnaire scores in the two groups were not significantly different.Discussion: Serum total testosterone and SHBG levels were lower in the MS group, and inversely proportional to this, insulin resistance and intensity of MS components were increased. Turk Jem 2013; 17: 22-7

  8. Age dependency of serum insulin - like growth factor (IGF-1 in healthy Turkish adolescents and adults.

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    Tiryakioaylu O

    2003-12-01

    Full Text Available BACKGROUND: Serum levels of insulin-like growth factor-1 (IGF-1 reflect endogenous growth hormone (GH secretion in healthy subjects. Measurements of IGF-1 are useful for diagnosis and follow-up of patients with acromegaly and the diagnosis of GH deficiency in children. AIMS: To assess age dependency and normal ranges of serum IGF-1 levels in healthy Turkish population. SETTING AND DESIGN: We therefore studied 272 healthy adolescents and adults between 15-75 years of age. None had diabetes or other endocrine disease or had received estrogen therapy. MATERIAL AND METHODS: Height, weight, body mass index (BMI and waist-hip ratio were measured in all subjects. Serum samples were obtained during morning hours and IGF-1 was measured by radioimmunoassay. STATISTICAL ANALYSIS: The age-dependent reference range for serum IGF-1 concentrations was calculated by simple least linear regression analysis: the regression line represents the means with 95 percent confidence intervals. Correlation analysis was also done. RESULTS: Ageing was negatively related to serum levels of IGF-1 (P= 0.0001, r=-0.931 with a mean decrease (youngest vs. oldest. IGF-1 levels increased during adolescence, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of IGF-1 was apparent. There were also a significant difference according to gender; females had significantly higher levels (357.909+/-219.167 mg/L than males (307.962+/-198.41 mg/L (P=0.012. IGF-1 levels were correlated with body height (P=0.001, r=0.223, body weight (P=0.002,r=-0.188 and BMI (P=0.039, r=0.128. CONCLUSION: IGF-1 serum levels increase in adolescents with a peak in puberty, whereafter IGF-1 levels return to prepubertal levels.

  9. Il-6 Serum Levels and Production Is Related to an Altered Immune Response in Polycystic Ovary Syndrome Girls with Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Anna M. Fulghesu

    2011-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is frequently characterized by obesity and metabolic diseases including hypertension, insulin resistance, and diabetes in adulthood, all leading to an increased risk of atherosclerosis. The present study aimed to evaluate serum and production of inflammatory markers in adolescent Sardinian PCOS. On the basis of HOMA findings, patients were divided into noninsulin resistant (NIR and insulin resistant (IR, and were weight- and age-matched with healthy girls. Inflammatory cytokines (TNF-α, IL-6, Il-10, TGF-β and lipokines (leptin, adiponectin, the reactant hs-CRP, and in vitro inflammatory lympho-monocyte response to microbial stimulus were evaluated. In healthy and PCOS subjects, leptin and hs-CRP were correlated with BMI, whereas adiponectin was significantly reduced in all PCOS groups. Although cytokines were similar in all groups, Interleukin-6 (IL-6 was significantly higher in IR PCOS. Moreover, in the latter group lipopolysaccharide-activated monocytes secreted significantly higher levels of IL-6 compared to NIR and control subjects. To conclude, IR PCOS displayed increased IL-6 serum levels and higher secretion in LPS-activated monocytes, whilst revealing no differences for other inflammatory cytokines. These results suggest that in PCOS patients an altered immune response to inflammatory stimuli is present in IR, likely contributing towards determining onset of a low grade inflammation.

  10. Modern approach to basal-bolus therapy with glargine and glulisine insulin analoguesin various age groups

    Directory of Open Access Journals (Sweden)

    N N Volevodz

    2013-03-01

    Full Text Available DCCT (Diabetes Control and Complications Trial study established that intensified insulin therapy in multiple daily injections (MDI or continuous insulin infusion (CSII regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus® and glulisine (Apidra® insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

  11. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes.

    Science.gov (United States)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte

    2016-03-31

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

  12. Impact of the Xba1-polymorphism of the human muscle glycogen synthase gene on parameters of the insulin resistance syndrome in a Danish twin population

    DEFF Research Database (Denmark)

    Fenger, M; Poulsen, P; Beck-Nielsen, H;

    2000-01-01

    : The Xba1-polymorphism of the human muscle glycogen synthase gene is correlated to insulin resistance and to diastolic blood pressure. The polymorphism does not involve any known transcription factor or any structural change in GYS1, and these correlations are therefore most probably caused by linkage......AIMS: To establish the impact on the insulin resistance syndrome of the intron 14 Xba1-polymorphism in human muscle glycogen synthase (GYS1). METHODS: Parameters related to the insulin resistance syndrome were measured in 244 monozygotic twins and 322 dizygotic twins with or without impaired...... and the remainder had the genotype A1A2. No A2A2-genotypes were detected. In 11 genotypic discordant dizygotic twin pairs the insulin resistance was significantly increased in the twins carrying the A1A2 genotype regardless of sex (HOMA index 1.81 (A1A1) vs. 2.57 (A1A2), P

  13. Insulin resistance in obesity and polycystic ovary syndrome: systematic review and meta-analysis of observational studies.

    Science.gov (United States)

    Behboudi-Gandevani, Samira; Ramezani Tehrani, Fahimeh; Rostami Dovom, Marzieh; Farahmand, Maryam; Bahri Khomami, Mahnaz; Noroozzadeh, Mahsa; Kabir, Ali; Azizi, Fereidoun

    2016-01-01

    We aimed at investigating whether insulin resistance (IR)/sensitivity are impaired in obese/non-obese polycystic ovary syndrome (PCOS) and obese/non-obese healthy controls. A comprehensive literature search was performed for observational, English language studies. Meta-analysis was performed with the random effects model according to the heterogeneity. Eligible studies, involving 3037 women in four groups of: 1-obese, PCOS; 2-non-obese, PCOS, 3-obese, non-PCOS and 4-Non-obese, non-PCOS were included. Based on the insulin resistance index (HOMA-IR) analysis, the pooled mean (95% Conf. Interval) of HOMA IR in groups 1-4 were 4.38 (3.84, 4.92), 2.68 (2.16, 3.20), 2.44 (2.06, 2.82) and 1.34 (1.06, 1.63), respectively. Meta-analysis showed that group 1 (obese, PCOS patients) statistically have the highest IR and group 4 (non-obese, non-PCOS women) have the highest insulin sensitivity. Group 2 (non-obese, PCOS patients) and group 3 (obese, non-PCOS women) were between this range and they had lower IR than group 1 (obese, PCOS) and lower insulin sensitivity than group 4 (non-obese, non-PCOS). So, there were statistical differences between all groups except between groups 2 and 3. Insulin sensitivity indexes (quickie and ISI), also confirm the IR index (HOMA-IR) results. Based on different IR/sensitivity indexes, we found no evidence of any different effects of BMI ≥ 30 kg/m(2) on IR/sensitivity. In conclusion, PCOS status intensifies the adverse effects of obesity on IR, it has to be appropriately addressed in primary and secondary preventive cares and treatments provided for these women.

  14. Dietary glycemic index during pregnancy is associated with biomarkers of the metabolic syndrome in offspring at age 20 years.

    Directory of Open Access Journals (Sweden)

    Inge Danielsen

    Full Text Available OBJECTIVE: Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI and glycemic load (GL during pregnancy and biomarkers of the metabolic syndrome in young adult offspring. METHODS: Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI, education, energy intake, and the offspring's ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. OUTCOME MEASURES: Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. RESULTS: Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units' GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02, insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01 and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01 in the offspring; whereas no associations were detected for GL. CONCLUSIONS: Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction.

  15. Gender differences of disturbed hemostasis related to fasting insulin level in healthy very elderly Japanese aged > or = 75 years.

    Science.gov (United States)

    Kario, K; Matsuo, T; Kobayashi, H; Sakata, T; Miyata, T; Shimada, K

    1995-08-01

    We investigated the relationship between fasting insulin level and various hemostatic factors, including fibrinolytic factors (active plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (tPA)-PAI-1 complex, plasmin-alpha 2-plasmin inhibitor (PIC), and D-dimer), coagulation factors (activated factor VII, factor VII coagulant activity and antigen, factor VIII, factor X, and fibrinogen), coagulation inhibitors (antithrombin III, heparin cofactor II, and protein C), and an acute phase marker (sialic acid) in 102 healthy individuals aged > or = 75 years (46 men and 56 women). Active PAI-1 levels had a significant negative correlation with PIC levels (r = -0.342, P = 0.0006), indicating that PAI-1 influences in vivo fibrinolytic activity in the very elderly. Gender differences were found in the relationship between insulin and hemostatic abnormalities, with the insulin level being positively correlated with coagulation factors in men (factor VIII activity: r = 0.422, P sex.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Combined lowering of low grade systemic inflammation and insulin resistance in metabolic syndrome patients treated with Ginkgo biloba.

    Science.gov (United States)

    Siegel, G; Ermilov, E; Knes, O; Rodríguez, M

    2014-12-01

    In a clinical pilot study with eleven metabolic syndrome patients, a simultaneous decrease in hs-CRP from 8.85 ± 4.09 to 4.92 ± 2.51 mg/L (-44.4%) (p Ginkgo biloba. Furthermore, both IL-6 (-12.9%, p < 0.0407) and nanoplaque formation (-14.3%, p < 0.0077) were additionally reduced. According to a large clinical trial elucidating the importance of insulin resistance and low-grade systemic inflammation for cardiovascular disease and overall mortality risk, these data might indicate a CVD/total mortality risk reduction.

  17. Adiposity in Children Born Small for Gestational Age Is Associated With β-Cell Function, Genetic Variants for Insulin Resistance, and Response to Growth Hormone Treatment

    DEFF Research Database (Denmark)

    Thankamony, Ajay; Jensen, Rikke Beck; O'Connell, Susan M

    2016-01-01

    secretion, and response to GH treatment in short children born small for gestational age (SGA). METHODS: In 89 short prepubertal SGA children (age, 6.2 ± 1.6 y; 55 boys) treated with GH for 1 year in a multicenter study, body fat percentage was estimated at baseline and 1 year using dual-energy x......-ray absorptiometry. The main outcome measures were treatment-related changes in height, IGF-1 standard deviation score, insulin sensitivity, insulin secretion, and disposition index. Combined multiallele gene scores based on single nucleotide polymorphisms with known associations with lower insulin sensitivity (gene...... scores for insulin resistance [GS-InRes]) and insulin secretion (gene scores for insulin secretion [GS-InSec]) were analyzed for their relationships with adiposity. RESULTS: Mean percentage body fat at baseline was low compared to normative data (P = .045) and decreased even further on GH treatment...

  18. mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of Metabolic Syndrome

    Science.gov (United States)

    Rovira, Jordi; Ramírez-Bajo, María Jose; Banon-Maneus, Elisenda; Moya-Rull, Daniel; Ventura-Aguiar, Pedro; Hierro-Garcia, Natalia; Lazo-Rodriguez, Marta; Revuelta, Ignacio; Torres, Armando; Oppenheimer, Federico; Campistol, Josep M.; Diekmann, Fritz

    2016-01-01

    Background Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β-cell toxicity. Methods Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, β-cell proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to analyze insulin content, insulin secretion, and gene expression. Results After 12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR. Treatment prolongation induced increase of area under the curve of IPGTT in LZR and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2 hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as well as insulin content. Insulin secretion was only affected in OZR. Islets from OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes related with insulin secretion remained unchanged or upregulated. Conclusions In conditions that require adaptive β-cell proliferation, SRL might reveal harmful effects by blocking β-cell proliferation, insulin production and secretion. These effects disappeared when removing the therapy. PMID:27500257

  19. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J;

    1999-01-01

    Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle tra...

  20. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  1. Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls.

    Science.gov (United States)

    Morrison, John A; Glueck, Charles J; Wang, Ping

    2010-05-01

    We evaluated the associations of teenage insulin and adolescent diet with 10-year weight gain in an analysis sample of black and white girls matched for pubertal stage, body mass index (BMI) (or fat mass), and insulin at ages 9 to 10 years. We hypothesized that preteen insulin and insulin resistance would interact with dietary factors to positively predict increases in BMI. Furthermore, we hypothesized that increased insulin and insulin resistance, interacting with higher caloric intake during adolescence, would lead to greater increments in BMI in black girls than in white girls. Prospective 10-year follow-up was performed on 215 pairs of black and white schoolgirls matched at baseline by BMI (or fat mass), insulin, and pubertal stage, with repeated measures of body habitus, insulin, and dietary intake. When matched for BMI, black girls had higher fat-free mass and white girls had higher fat mass at ages 9 to 10 years. Black-white differences in caloric intake were not significant at ages 9 to 10 years, but black girls consumed more calories at age 19 years. Black girls consumed a greater percentage of calories from fat throughout. At age 19 years, black girls had higher BMI, fat mass index, and insulin. When matched at ages 9 to 10 years for fat mass, black girls were heavier, had higher BMI, and had greater fat-free mass. By ages 18 to 19 years, black girls continued to have higher BMI, but had accrued higher fat mass and a higher percentage of body fat. By stepwise multiple regression, 10-year increases in BMI were predicted by ages 9 to 10 years BMI, 10-year change in insulin, and a 3-way interaction between ages 9 to 10 years insulin, adolescent caloric intake, and race (higher in black girls) (all Ps < .0001). Insulin at ages 9 to 10 years interacts with caloric intake to increase BMI by age 19 years. There appear to be intrinsic black-white metabolic differences that lead to greater gains in fat during adolescence in black girls. Evaluating BMI and insulin

  2. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2015-12-01

    Full Text Available Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA groups than that of appropriate for gestational age (AGA groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes.

  3. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

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    Dinka Pavicic Baldani

    2015-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

  4. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity.

    Science.gov (United States)

    Rivas, Donato A; McDonald, Devin J; Rice, Nicholas P; Haran, Prashanth H; Dolnikowski, Gregory G; Fielding, Roger A

    2016-04-01

    The loss of skeletal muscle mass is observed in many pathophysiological conditions, including aging and obesity. The loss of muscle mass and function with aging is defined as sarcopenia and is characterized by a mismatch between skeletal muscle protein synthesis and breakdown. Characteristic metabolic features of both aging and obesity are increases in intramyocellular lipid (IMCL) content in muscle. IMCL accumulation may play a mechanistic role in the development of anabolic resistance and the progression of muscle atrophy in aging and obesity. In the present study, aged and high-fat fed mice were used to determine mechanisms leading to muscle loss. We hypothesized the accumulation of bioactive lipids in skeletal muscle, such as ceramide or diacylglycerols, leads to insulin resistance with aging and obesity and the inability to activate protein synthesis, contributing to skeletal muscle loss. We report a positive association between bioactive lipid accumulation and the loss of lean mass and muscle strength. Obese and aged animals had significantly higher storage of ceramide and diacylglycerol compared with young. Furthermore, there was an attenuated insulin response in components of the mTOR anabolic signaling pathway. We also observed differential increases in the expression of inflammatory cytokines and the phosphorylation of IκBα with aging and obesity. These data challenge the accepted role of increased inflammation in obesity-induced insulin resistance in skeletal muscle. Furthermore, we have now established IκBα with a novel function in aging-associated muscle loss that may be independent of its previously understood role as an NF-κB inhibitor.

  5. Increased insulin-like growth factor-1 in relation to cardiovascular function in polycystic ovary syndrome: friend or foe?

    Science.gov (United States)

    Desai, Namrata Ajaykumar; Patel, Snehal S

    2015-10-01

    The incidence of cardiovascular disease (CVD) in patients with polycystic ovary syndrome (PCOS) is very high and conventional risk factors only partially explain excessive risk of developing CVD in patients of PCOS. The pathophysiology of PCOS is very unique, and several hormonal and metabolic changes occur. Several observations suggest that serum IGF-1 levels decrease in insulin resistance, which results in IGF-1 deficiency. In patient of PCOS, close relationships have been demonstrated between insulin resistance and serum IGF-1 levels. Hyperinsulinemic insulin resistance results in a general augmentation of steroidogenesis and LH release in PCOS. The action of IGF-1 varies in different tissues possibly via autocrine or paracrine mechanisms. The increase or decrease in IGF-1 in different tissues results in differential outcomes. Several studies suggest that lowered circulating IGF-1 levels play important role in the initiation of the cardiac hypertrophic response which results in the risk of cardiovascular disease. While recent results suggests that individual with elevated IGF-1 is protected against cardiovascular disease. Thus IGF-1 shows versatile pleiotropic actions. This review provides a current perspective on increased level of IGF-1 in PCOS and also adds to the current controversy regarding the roles of IGF-1 in cardiovascular disease.

  6. The Estimation of First-Phase Insulin Secretion by Using Components of the Metabolic Syndrome in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Jiunn-diann Lin

    2015-01-01

    Full Text Available Aims. There are two phases of insulin secretion, the first (FPIS and second phase (SPIS. In this study, we built equations to predict FPIS with metabolic syndrome (MetS components and fasting plasma insulin (FPI. Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg was obtained. The AIRg was considered as FPIS. Results. When MetS components were only used, the following equation was built: log (FPIS = 1.477 − 0.119 × fasting plasma glucose (FPG + 0.079 × body mass index (BMI − 0.523 × high-density lipoprotein cholesterol (HDL-C. After FPI was added, the second equation was formulated: log (FPIS = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI, which provided a better accuracy than the first one. Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice.

  7. Effect of glabridinon on insulin resistance, C-reactive protein and endothelial function in young women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Bing-Guo Luan

    2015-08-01

    Full Text Available In the present study 32 women with polycystic ovary syndrome were treated with glabridin (10 µM daily for 12 months. The results revealed a significant reduction in serum testosterone from 95.3 ± 23.6 to 49.8 ± 12.7 ng/dL and fasting insulin concentrations from 12.3 ± 5.2 to 8.11 ± 3.42 U/mL after glabridin treatment. It also leads to a marked improvement in insulin resistance indices and reduction in hirsutism score from 12.8 ± 3.2 to 7.0 ± 3.5. More interestingly, all the women reverted to regular menstrual cycles. The sex hormone-binding globulin level increased significantly from 23.1 ± 5.6 to 52.5 ± 15.8 nmol/L after glabridin treatment. The levels of serum hsCRP decreased from 0.32 ± 0.08 to 0.06 ± 0.01 mg/dL and that of endothelium-dependent vascular responses from 17.2 ± 4.3 to 8.8 ± 2.4% after glabridin treatment. Therefore, glabridin acts as a potent candidate for the improve-ment of insulin sensitivity and androgen production.

  8. Age-related changes in insulin sensitivity and β-cell function among European American and African American women

    Science.gov (United States)

    Chandler-Laney, P. C.; Phadke, R.; Granger, W. M.; Fernández, J. R.; Muñoz, A. J.; Man, C. Dalla; Cobelli, C.; Ovalle, F.; Gower, B. A.

    2011-01-01

    Type 2 diabetes is more prevalent among African American (AA) than European American (EA) women for reasons that are unknown. Ethnic differences in physiological processes related to insulin sensitivity and secretion, and age-related changes in these processes, may play a role. The purpose of this study was to identify ethnicity- and age-related differences in insulin sensitivity and β-cell responsivity among AA and EA females, and to determine whether these differences are independent of body composition and fat distribution. Healthy, normoglycemic females aged 7–12 yr (n=62), 18–32 yr (n=57), and 40–70 yr (n=49) were recruited for entry into this study. Following an overnight fast, insulin sensitivity (SI), intravenous glucose tolerance (Kg), acute C-peptide secretion (X0), and basal, first-phase, second-phase, and total β-cell responsivity to glucose (PhiB, Phi1, Phi2, and PhiTOT, respectively) were measured by an intravenous glucose tolerance test. Total % body fat was assessed by dual-energy X-ray absorptiometry, and intra-abdominal adiposity (IAAT) by computed tomography. Main effects of age group and ethnicity were measured with ANCOVA, adjusting for %fat, IAAT, and SI as indicated. AA had lower SI, and higher Kg, X0, Phi1, and PhiTOT (P<0.05), which remained after adjustment for %fat and IAAT. Greater X0, Phi1, and PhiTOT among AA were independent of SI. Advancing age was associated with greater Phi2 among both EA and AA. To conclude, inherent ethnic differences in β-cell function exist independently of adiposity and insulin sensitivity. Future research should examine whether ethnic differences in β-cell physiology contribute to disparities in type 2 diabetes risk. PMID:20885386

  9. Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling.

    Directory of Open Access Journals (Sweden)

    Minhua Zhang

    2009-11-01

    Full Text Available How dietary restriction (DR increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1 is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Abeta42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Abeta42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Abeta42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway.

  10. Triiodothyronine : a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, SJL; ter Maaten, JC; Popp-Snijders, C; Heine, RJ; Gans, ROB

    1999-01-01

    Objective Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis a

  11. Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging.

    Science.gov (United States)

    Patterson, David; Cabelof, Diane C

    2012-04-01

    Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate metabolism and oxidative stress in the dysregulation of BER in Down syndrome. Further, we suggest these pathways are involved in the leukemogenesis of Down syndrome. We have reviewed the role of BER in the processing of oxidative stress, and the impact of folate depletion on BER capacity. Further, we have reviewed the role that loss of BER, specifically DNA polymerase beta, plays in accelerating the rate of aging. Like that seen in the DNA polymerase beta heterozygous mouse, the aging phenotype of Down syndrome is subtle, unlike the aging phenotypes seen in the classical progeroid syndromes and mouse models of aging. As such, Down syndrome may provide a model for elucidating some of the basic mechanisms of aging.

  12. Short-term antidiabetic treatment with insulin or metformin has a similar impact on the components of metabolic syndrome in women with gestational diabetes mellitus requiring antidiabetic agents: results of a prospective, randomised study.

    Science.gov (United States)

    Zawiejska, A; Wender-Ozegowska, E; Grewling-Szmit, K; Brazert, M; Brazert, J

    2016-04-01

    Gestational diabetes mellitus (GDM) is associated with an increased prevalence of fetal and maternal complications primarily caused by maternal hyperglycemia, which results in abnormal fetal growth. Diet modification is a common first step in the treatment of GDM, followed by antidiabetic pharmacotherapy if this approach fails. Insulin therapy is generally accepted; however, oral hypoglycemic agents have been used in this population. In this prospective, randomised study, we compared maternal metabolic status after treatment with insulin or metformin. Pregnant women (gestational age: ≥ 20 weeks) with GDM requiring medical hypoglycemic treatment were randomly allocated to the Metformin (n = 35) or Insulin (n = 43) Groups. Maternal metabolic status - assessed by glycated hemoglobin (HBA1c) level, glycemic profile, insulin concentration, Homeostatic Model Assessment - Insulin Resistance index, and lipids - was recorded at booking and throughout pregnancy. The characteristics of the study group were: maternal age 33.5 ± 5.9 years, gestational age at baseline 28.5 ± 3.5 weeks, prepregnancy body mass index (BMI) 32.2 ± 3.5 kg/m(2), HbA1c at baseline 5.6 ± 0.6%, and average daily glycemia 5.9 ± 0.6 mmol/dl. Fasting glycemia at term was significantly lower in the Insulin Group but there were no significant differences in mean daily glycemia, HbA1c and BMI at term between the groups. Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group. Both fasting and average daily glycemia were significantly reduced following treatment in both groups. No such change was evident for HbA1c. In a relative risk analysis, metformin treatment was associated with an insignificant elevated risk of HbA1c, triglycerides and lipid indices falling within the

  13. Normal ageing in adults with Down's syndrome: a longitudinal study.

    Science.gov (United States)

    Devenny, D A; Silverman, W P; Hill, A L; Jenkins, E; Sersen, E A; Wisniewski, K E

    1996-06-01

    The ubiquitous presence of the neuropathology of Alzheimer disease (AD) in individuals with Down's syndrome (DS) over 40 years of age suggests that this group of people will exhibit a high prevalence of dementia of the Alzheimer type (DAT) as they age. The present study indicates that there is a clear discrepancy between the presumed presence of AD neuropathology and the clinical expression of DAT among older people with DS. In the first 6 years of a longitudinal study, the present authors compared 91 adults (31-63 years of age) with DS and mild or moderate mental retardation to 64 adults (31-76 years of age) with other forms of mental retardation (MR) on yearly measures of mental status, short- and long-term memory, speeded psychomotor function, and visuospatial organization. The results indicated that, over repeated testing on the verbal long-term memory test, younger participants with DS showed small increases in their scores, while older participants with DS showed very slight decreases. Overall performance scores on this test and a speeded psychomotor task were poorer for both diagnostic groups in individuals aged 50 years and older. The magnitude and type of these selective changes in performance were consistent with performance profiles observed in older healthy adults without mental retardation on tests measuring similar cognitive functions. Only four out of the 91 people with DS in the present sample showed changes in functioning that have led to a diagnosis of possible DAT, and in these individuals, alternative causes of performance declines were concurrently present (e.g. thyroid dysfunction). These findings indicate that some age-associated changes in functioning are related to "normal' but probably precocious ageing among adults with DS. Furthermore, these findings suggest that adults with DS and mild or moderate mental retardation may be at lower risk for dementia during their fourth and fifth decades of life than previous studies have suggested.

  14. CEREBROCARDIAC SYNDROME ON PATIENTS OF OVER SEVENTY AGE AND EEG STUDY

    Institute of Scientific and Technical Information of China (English)

    LIU Mingshun; MEI Fengjun; LI Fengluan; LIU Qingrui; GU Lanjie

    2005-01-01

    Objectives: To observe cerebrocardiac syndrome on patients of the over seventy age and it's change of EEG. Methods: Brain CT and ECG were examined in 50 patients of the over seventy age with cerebrocardiac syndrome. Results: There were obvious changes in the brain CT and ECG. Conclusion:There were obvious changes of brain CT and ECG in cerebrocardiac syndrome of over seventy age patients.

  15. Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome.

    Science.gov (United States)

    Limoge, Floriane; Faivre, Laurence; Gautier, Thomas; Petit, Jean-Michel; Gautier, Elodie; Masson, David; Jego, Gaëtan; El Chehadeh-Djebbar, Salima; Marle, Nathalie; Carmignac, Virginie; Deckert, Valérie; Brindisi, Marie-Claude; Edery, Patrick; Ghoumid, Jamal; Blair, Edward; Lagrost, Laurent; Thauvin-Robinet, Christel; Duplomb, Laurence

    2015-12-01

    Cohen Syndrome (CS) is a rare autosomal recessive disorder, with defective glycosylation secondary to mutations in the VPS13B gene, which encodes a protein of the Golgi apparatus. Besides congenital neutropenia, retinopathy and intellectual deficiency, CS patients are faced with truncal obesity. Metabolism investigations showed abnormal glucose tolerance tests and low HDL values in some patients, and these could be risk factors for the development of diabetes mellitus and/or cardiovascular complications. To understand the mechanisms involved in CS fat storage, we used two models of adipogenesis differentiation: (i) SGBS pre-adipocytes with VPS13B invalidation thanks to siRNA delivery and (ii) CS primary fibroblasts. In both models, VPS13B invalidation led to accelerated differentiation into fat cells, which was confirmed by the earlier and increased expression of specific adipogenic genes, consequent to the increased response of cells to insulin stimulation. At the end of the differentiation protocol, these fat cells exhibited decreased AKT2 phosphorylation after insulin stimulation, which suggests insulin resistance. This study, in association with the in-depth analysis of the metabolic status of the patients, thus allowed us to recommend appropriate nutritional education to prevent the occurrence of diabetes mellitus and to put forward recommendations for the follow-up of CS patients, in particular with regard to the development of metabolic syndrome. We also suggest replacing the term obesity by abnormal fat distribution in CS, which should reduce the number of inappropriate diagnoses in patients who are referred only on the basis of intellectual deficiency associated with obesity.

  16. Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Margareth Chiharu Iwata

    2015-06-01

    Full Text Available Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS using metformin or combined oral contraceptive (COC after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16; II-metformin (850mg 12/12h, n=16; III-COC plus metformin (n=9. Body mass index (BMI, acne (% of improvement, modified Ferriman-Gallway index and menstrual cycle index (MCI, luteinizing hormone (LH, follicle-stimulating hormone (FSH, total testosterone (TT, androstenedione (A and homeostasis model assessment: insulin resistance (HOMA-IR index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007. The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046. The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75, showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

  17. Acute coronary syndrome in women of reproductive age

    Directory of Open Access Journals (Sweden)

    Idris N

    2011-11-01

    Full Text Available Nazimah Idris1, Sharifah Sulaiha Aznal1, Sze-Piaw Chin1, Wan Azman Wan Ahmad2, Azhari Rosman3, Sinnadurai Jeyaindran4, Omar Ismail5, Robaayah Zambahari3, Kui Huan Sim6 1International Medical University, Seremban; 2University Malaya Medical Centre, PJ; 3Institut Jantung Negara, KL; 4Hospital Kuala Lumpur, KL; 5Hospital Pulau Pinang; 6Hospital Umum Sarawak, Malaysia Background: There is scarce or no data on prevalence and presentation of acute coronary syndrome (ACS among women of reproductive age. Furthermore, whether women of reproductive age presenting with ACS have the same risk factors as men and older women is not known. Objective: To analyze factors associated with ACS in women of reproductive age in comparison with older women and men of a similar age group. Methodology: A total of 9702 cases of acute coronary syndrome over a 3-year period (2006–2008 from the National Cardiovascular Disease database were analyzed, with focus on women of reproductive age (20–<40 years, looking into association with ethnicity, comorbid illness, and the ACS stratum. Comparison with older women (40–<60 years; Control 1 and men of similar age group (Control 2 was made and analyzed using Fisher's exact test and chi-square test when necessary. Results: From a total of 9702 cases, 2344 (24.2% were women. Of these, 45 (1.9% were women between 20 and <40 years, which is significantly lower than the two controls (older women 30.8%, and men of same age 6.2%, respectively; P < 0.0001. The distribution of ethnicity shows a similar pattern between the study group and the controls, but patients of Indian ethnicity were over-represented when compared with the Malaysian demographics of general population (31.3% versus 7.1%; P < 0.0001. ACS in women of reproductive age was associated with diabetes mellitus in 37.8%, hypertension in 40.0%, and dyslipidemia in 24.4% of cases, similar to men of the same age but significantly lower than the older women (P < 0.0001. Smoking

  18. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  19. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

    Directory of Open Access Journals (Sweden)

    Liang Shu-Fen

    2006-04-01

    Full Text Available Abstract Background Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR. The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP with Bst N1 used for codon 972 and Dra III for codon 513. Results AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%. None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated

  20. The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome

    Science.gov (United States)

    Pourfarzam, Morteza; Zadhoush, Fouzieh; Sadeghi, Masoumeh

    2016-01-01

    Background: Insulin resistance (IR) is associated with low-grade systemic inflammation. It plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in patients with metabolic syndrome (MetS). It is unclear whether diabetic patients with MetS confer elevated CVD risk and outcomes beyond the impact of individual's components of MetS. The aim of this study is to highlight the central role of IR, inflammation, triglyceride/high-density lipoprotein- cholesterol (TG/HDL-C) ratio, and atherogenic index of plasma (AIP) in T2DM with MetS. Materials and Methods: This cross-sectional study comprised 130 men distributed into three groups, namely Controls: 40 nondiabetic healthy volunteers; Group I: 40 T2DM patients without MetS, and Group II: 50 T2DM patients with MetS. Fasting blood samples were collected for the measurement of blood lipid profile, glucose, insulin, hemoglobin A1c, and high-sensitivity C-reactive protein (hs-CRP). TG/HDL-C ratio, AIP, and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Results: Significant positive association was observed between HOMA-IR and hs-CRP only in Group II and between HOMA-IR and TG/HDL-C ratio in all subjects. Significant differences were seen in waist and hip circumferences, waist/hip ratio, body mass index, systolic blood pressure, fasting blood glucose, TGs, HDL-C, insulin, hs-CRP, HOMA-IR, TG/HDL ratio, and AIP between Controls and Group I with Group II. Conclusions: In T2DM with MetS, coexistence of elevated atherogenic indices, systemic inflammation, and association between HOMA-IR and TG/HDL-C ratio were seen. These factors are considered having important role in elevated CVD risk beyond MetS components in these patients. PMID:27713874

  1. Longevity Pathways (mTOR, SIRT, Insulin/IGF-1) as Key Modulatory Targets on Aging and Neurodegeneration.

    Science.gov (United States)

    Mazucanti, Caio Henrique; Cabral-Costa, João Victor; Vasconcelos, Andrea Rodrigues; Andreotti, Diana Zukas; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2015-01-01

    Recent data from epidemiologic studies have shown that the majority of the public health costs are related to age-related disorders, and most of these diseases can lead to neuronal death. The specific signaling mechanisms underpinning neurodegeneration and aging are incompletely understood. Much work has been directed to the search for the etiology of neurodegeneration and aging and to new therapeutic strategies, including not only drugs but also non-pharmacological approaches, such as physical exercise and low-calorie dietary intake. The most important processes in aging-associated conditions, including neurodegeneration, include the mammalian (or mechanistic target of rapamycin (mTOR, sirtuin (SIRT and insulin/insulin growth factor 1 signaling (IIS pathways. These longevity pathways are involved in an array of different processes, including metabolism, cognition, stress response and brain plasticity. In this review we focus on the current advances involving the mTOR, SIRT and IIS longevity pathways during the course of healthy aging processes and neurodegenerative diseases, bringing new insights in the form of a better understanding of the signaling mechanisms underpinning neurodegeneration and how these differ from physiological normal aging processes. This also provides new targets for the therapeutic management and/or prevention of these devastating age-related disorders.

  2. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

    Science.gov (United States)

    Pacenza, Néstor; Pasqualini, Titania; Gottlieb, Silvia; Knoblovits, Pablo; Costanzo, Pablo R.; Stewart Usher, Jorge; Rey, Rodolfo A.; Martínez, María P.; Aszpis, Sergio

    2012-01-01

    The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases. PMID:22291701

  3. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

    Directory of Open Access Journals (Sweden)

    Néstor Pacenza

    2012-01-01

    Full Text Available The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%. Most of the patients (83.7% showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases.

  4. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

    DEFF Research Database (Denmark)

    Bacos, Karl; Gillberg, Linn; Volkov, Petr;

    2016-01-01

    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA...... methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes...... demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D....

  5. The effects of exercise on C-reactive protein, insulin, leptin and some cardiometabolic risk factors in Egyptian children with or without metabolic syndrome

    OpenAIRE

    Kamal Nashwa; Ragy Merhan

    2012-01-01

    Abstract Background The prevalence and magnitude of obesity in the children and the adolescents have increased dramatically in the developing countries over the last 20–30 years. The prevalence of metabolic syndrome (MS) in children is increasing. Aim: This study aimed to investigate the changes of C-reactive protein (CRP), leptin, insulin, and blood lipids before and after the exercise therapy in normal and obese children (with or without metabolic syndrome). Methods The study covered 49 nor...

  6. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    Directory of Open Access Journals (Sweden)

    Julia Johansson

    Full Text Available In rats with dihydrotestosterone (DHT-induced polycystic ovary syndrome (PCOS, repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4 by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b, but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity

  7. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    Science.gov (United States)

    Johansson, Julia; Mannerås-Holm, Louise; Shao, Ruijin; Olsson, AnneLiese; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2013-01-01

    In rats with dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat) and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4) by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b), but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity were affected by

  8. 胰岛素抵抗和多囊卵巢综合征%Insulin resistance and polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    母义明; 刘敏

    2013-01-01

    Insulin resistance likely plays a central pathogenic role in polycystic ovary syndrome and may explain the pleiotropie presentation and involvement of multiple organ systems.Hyperinsulinaemia leads to increased production of androgens resulting in anovulatory infertility.Women,especially those obese women with polycystic ovary syndrome,have an increased risk of developing type 2 diabetes and cardiovascular disease in their later life.Treatment of insulin resistance through lifestyle therapy or with a diabetes drug has become mainstream therapy to reduce the risk of diabetes,endometrial abnormalities,and cardiovascular disease events in women with polycystic ovary syndrome.%胰岛素抵抗在多囊卵巢综合征发病机制中起核心作用,其与患者的多重症状和多器官受累密切相关.高胰岛素血症不仅导致患者雄激素水平升高从而引起无排卵性不孕,同时使患者(尤其是肥胖患者)未来发生2型糖尿病和心血管疾病的风险增加.通过生活方式干预和糖尿病药物改善患者胰岛素抵抗以降低糖尿病、子宫内膜异常和心血管疾病的发生风险是多囊卵巢综合征的主要治疗手段.

  9. Bloom syndrome in short children born small for gestational age: A challenging diagnosis

    NARCIS (Netherlands)

    J.S. Renes (Judith); R.H. Willemsen (Ruben); A. Wagner (Anja); M.J. Finken (Martijn); A.C.S. Hokken-Koelega (Anita)

    2013-01-01

    textabstractBackground: GH treatment has become a frequently applied growth-promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, eg, chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characte

  10. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β -Cell Mass in Middle-Aged Obese Diabetic Mice.

    Science.gov (United States)

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; McMillan, Ryan; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew; Liu, Dongmin

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction.

  11. Low serum insulin in traditional Pacific Islanders--the Kitava Study.

    Science.gov (United States)

    Lindeberg, S; Eliasson, M; Lindahl, B; Ahrén, B

    1999-10-01

    Increased serum insulin is related to abdominal obesity and high blood pressure in affluent societies where insulin, weight, and blood pressure typically increase with age. The increased insulin level has been thought to reflect insulin resistance, a well-known associated factor in the metabolic syndrome. In most nonwesternized populations, body weight and blood pressure do not increase with age and abdominal obesity is absent. However, it is not known whether serum insulin likewise does not increase with age in nonwesternized societies. Fasting levels of serum insulin were measured cross-sectionally in 164 subsistence horticulturalists aged 20 to 86 years in the tropical island of Kitava, Trobriand Islands, Papua New Guinea, and in 472 randomly selected Swedish controls aged 25 to 74 years from the Northern Sweden WHO Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) Study. In Kitava, the intake of Western food is negligible and stroke and ischemic heart disease are absent or rare. The body mass index (BMI) and diastolic blood pressure are low in Kitavans. The main outcome measures in this study were the means, distributions, and age relations of serum insulin in males and females of the two populations. Serum fasting insulin levels were lower in Kitava than in Sweden for all ages (P < .001). For example, the mean insulin concentration in 50- to 74-year-old Kitavans was only 50% of that in Swedish subjects. Furthermore, serum insulin decreased with age in Kitava, while it increased in Sweden in subjects over 50 years of age. Moreover, the age, BMI, and, in females, waist circumference predicted Kitavan insulin levels at age 50 to 74 years remarkably well when applied to multiple linear regression equations defined to predict the levels in Sweden. The low serum insulin that decreases with age in Kitavans adds to the evidence that a Western lifestyle is a primary cause of insulin resistance. Low serum insulin may partly explain the low

  12. Insulin resistance syndromes of monogenic mutations%单基因突变所致的胰岛素抵抗综合征

    Institute of Scientific and Technical Information of China (English)

    江珊; 贾伟平

    2009-01-01

    Several insulin resistance syndromes, such as severe insulin resistance syndrome caused by mutations of insulin receptor gene and lipodystrophy caused by mutations of lamin gene, have been characterized clinically. The gene mutations, pathogenesis and clinical features of these monogenie diseases were reviewed in this article.%临床上存在多种由单基因突变所导致的胰岛素抵抗综合征,如胰岛素受体基因突变造成的严重胰岛素抵抗综合征,核纤层蛋白(LMNA)基因突变导致的脂肪营养不良综合征等,以下将对这些疾病的临床特点、突变基因及发病机制作一综述.

  13. The association between the metabolic syndrome and alanine amino transferase is mediated by insulin resistance via related metabolic intermediates (the Cohort on diabetes and atherosclerosis Maastricht (CODAM) study)

    NARCIS (Netherlands)

    Jacobs, M.; Greevenbroek, van M.M.J.; Kallen, van der C.J.H.; Ferreira, I.; Feskens, E.J.M.; Jansen, E.H.J.M.; Schalkwijk, C.G.; Stehouwer, C.D.A.

    2011-01-01

    The metabolic syndrome is associated with nonalcoholic fatty liver disease (NAFLD) as well as with insulin resistance, inflammatory adipokines, endothelial dysfunction, and higher plasma levels of nonesterified fatty acids (NEFA), all of which may also affect the development of NAFLD. Therefore, we

  14. Single nucleotide polymorphisms (SNPs) involved in insulin resistance, weight regulation, lipid metabolism and inflammation in relation to metabolic syndrome: an epidemiological study

    NARCIS (Netherlands)

    Povel, C.M.; Boer, J.M.A.; Onland-Moret, N.; Dolle, M.E.; Feskens, E.J.M.; Schouw, van der Y.T.

    2012-01-01

    Background: Mechanisms involved in metabolic syndrome (MetS) development include insulin resistance, weight regulation, inflammation and lipid metabolism. Aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) involved in these mechanisms with MetS. Methods: In

  15. The Use of Mouse Models for Understanding the Biology of Down Syndrome and Aging

    OpenAIRE

    Vacano, Guido N.; Nathan Duval; David Patterson

    2012-01-01

    Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress ...

  16. Ablation of the transcriptional regulator Id1 enhances energy expenditure, increases insulin sensitivity, and protects against age and diet induced insulin resistance, and hepatosteatosis.

    Science.gov (United States)

    Satyanarayana, Ande; Klarmann, Kimberly D; Gavrilova, Oksana; Keller, Jonathan R

    2012-01-01

    Obesity is a major health concern that contributes to the development of diabetes, hyperlipidemia, coronary artery disease, and cancer. Id proteins are helix-loop-helix transcription factors that regulate the proliferation and differentiation of cells from multiple tissues, including adipocytes. We screened mouse tissues for the expression of Id1 and found that Id1 protein is highly expressed in brown adipose tissue (BAT) and white adipose tissue (WAT), suggesting a role for Id1 in adipogenesis and cell metabolism. Id1(-/-) mice are viable but show a significant reduction in fat mass (P<0.005) over the life of the animal that was not due to decreased number of adipocytes. Analysis of Id1(-/-) mice revealed higher energy expenditure, increased lipolysis, and fatty acid oxidation, resulting in reduced triglyceride accumulation in WAT compared to Id1(+/+) mice. Serum levels of triglycerides (193.9±32.2 vs. 86.5±33.8, P<0.0005), cholesterol (189.4±33.8 vs. 110.6±8.23, P<0.0005) and leptin (1263±835 vs. 222±260, P<0.005) were significantly lower in aged Id1(-/-) mice compared to Id1(+/+) mice. Id1-deficient mice have higher resting (P<0.005) and total (P<0.05) O(2) consumption and lower respiratory exchange ratio (P<0.005), confirming that Id1(-/-) mice use a higher proportion of lipid as an energy source for the increased energy expenditure. The expression of PGC1α and UCP1 were 2- to 3-fold up-regulated in Id1(-/-) BAT, suggesting that loss of Id1 increases thermogenesis. As a consequence of higher energy expenditure and reduced fat mass, Id1(-/-) mice displayed enhanced insulin sensitivity. Id1 deficiency protected mice against age- and high-fat-diet-induced adiposity, insulin resistance, and hepatosteatosis. Our findings suggest that Id1 plays a critical role in the regulation of energy homeostasis and could be a potential target in the treatment of insulin resistance and fatty liver disease.

  17. Investigations on the role of insulin and scorpion antivenom in scorpion envenoming syndrome

    Directory of Open Access Journals (Sweden)

    K. Radha Krishna Murthy

    2003-01-01

    Full Text Available Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg. followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, platelet count, red blood cell (RBC count, hemoglobin (Hb, 2,3-diphosphoglycerate (2,3-DPG, and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio. Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or

  18. Altered Nuclear Functions in Progeroid Syndromes: a Paradigm for Aging Research

    Directory of Open Access Journals (Sweden)

    Baomin Li

    2009-01-01

    Full Text Available Syndromes of accelerated aging could provide an entry point for identifying and dissecting the cellular pathways that are involved in the development of age-related pathologies in the general population. However, their usefulness for aging research has been controversial, as it has been argued that these diseases do not faithfully reflect the process of natural aging. Here we review recent findings on the molecular basis of two progeroid diseases, Werner syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, and highlight functional connections to cellular processes that may contribute to normal aging.

  19. Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women

    NARCIS (Netherlands)

    A.E. Hak (Liesbeth); C.D. Stehouwer (Coen); M.L. Bots (Michiel); K.H. Polderman; C.G. Schalkwijk (Casper); I.C.D. Westendorp (Iris); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    1999-01-01

    textabstractObesity, the insulin resistance syndrome, and atherosclerosis are closely linked and may all be determinants of an increased acute-phase response. In this study, we examined the relationship of C-reactive protein (CRP) with measures of obesity, variables of

  20. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect?

    Science.gov (United States)

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

    2017-03-01

    There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with less severe symptoms and better psychosocial functioning than presentation in childhood or younger adolescence. Ninety-four CAD (age 9-18) meeting Attenuated Psychosis Syndrome criteria participated in the study. The sample was divided and compared according to the age of presentation of Attenuated Psychosis Syndrome (9-14 vs 15-18 years). The predictive value of age of Attenuated Psychosis Syndrome presentation was investigated using receiver operating characteristic (ROC)-curve calculations. The two Attenuated Psychosis Syndrome groups were homogeneous in terms of gender distribution, IQ scores and comorbid diagnoses. Older Attenuated Psychosis Syndrome patients showed better functioning and lower depressive scores. ROC curves revealed that severity of functional impairment was best predicted using an age of presentation cut-off of 14.9 years for social functioning and 15.9 years for role functioning. This study partially confirmed our hypothesis; older age at presentation of Attenuated Psychosis Syndrome was associated with less functional impairment, but age was not associated with psychotic symptoms.

  1. Variability of the Aging Process in Dementia-Free Adults with Down Syndrome

    Science.gov (United States)

    Tsao, Raphaele; Kindelberger, Cecile; Freminville, Benedicte; Touraine, Renaud; Bussey, Gerald

    2015-01-01

    The aim of this cross-sectional study was to analyze the typical aging process in adults with Down syndrome, focusing on its variability. The sample comprised 120 adults with Down syndrome who were free of dementia. Ages ranged from 20 to 69 years. Each participant was assessed on cognitive functioning and social adaptation, and was checked for…

  2. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents : Is there an age effect?

    NARCIS (Netherlands)

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

    2017-01-01

    There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with l

  3. Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M

    2013-01-01

    Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), ...

  4. Acute High-intensity Interval Exercise-induced Redox Signaling is Associated with Enhanced Insulin Sensitivity in Obese Middle-aged Men.

    Directory of Open Access Journals (Sweden)

    Lewan Parker

    2016-09-01

    Full Text Available Background. Obesity and ageing are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK, and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods. Participants completed a 2 hour hyperinsulinaemic-euglycaemic clamp at rest, and 60 minutes after HIIE (4x4 mins at 95% HRpeak; 2 min recovery periods, separated by 1-3 weeks. Results. Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SAPK phosphorylation (JNK, p38 MAPK and NF-κB and SOD activity (p<0.05. Conclusion. These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 hours after HIIE.

  5. Cerebrovascular contributions to aging and Alzheimer's disease in Down syndrome.

    Science.gov (United States)

    Wilcock, Donna M; Schmitt, Frederick A; Head, Elizabeth

    2016-05-01

    Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

  6. Mechanisms of premature vascular aging in children with Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Gerhard-Herman, Marie; Smoot, Leslie B; Wake, Nicole; Kieran, Mark W; Kleinman, Monica E; Miller, David T; Schwartzman, Armin; Giobbie-Hurder, Anita; Neuberg, Donna; Gordon, Leslie B

    2012-01-01

    Hutchinson-Gilford progeria syndrome is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in Hutchinson-Gilford progeria syndrome and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean: 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and sex-matched controls in the intima-media (Pprogeria syndrome. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in Hutchinson-Gilford progeria syndrome provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population.

  7. Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Zvi

    2008-03-01

    Laron syndrome (LS, congenital primary GH insensitivity) is caused by deletions or mutations in the GH receptor gene, resulting in an inability to generate insulin-like growth factor-I (IGF-I). If untreated, the deficiency of IGF-I results in severe dwarfism, as well as skeletal and muscular underdevelopment. The only treatment is the daily administration of recombinant IGF-I. This review summarizes the present experience by several groups worldwide. The main conclusions are: A. The one or two injections regimen result in the same growth velocity; B. The growth velocity obtained with IGF-I administration is smaller than that observed with hGH in children with congenital isolated GH deficiency; C. Overdosage of IGF-I causes a series of adverse effects which can be avoided by carefully monitoring the serum IGF-I and GH levels.

  8. Metabolic Syndrome in Children and Adolescents: a Critical Approach Considering the Interaction between Pubertal Stage and Insulin Resistance.

    Science.gov (United States)

    Reinehr, Thomas

    2016-01-01

    Pediatricians increasingly diagnose the metabolic syndrome (MetS) in recent years to describe cardiovascular risk and to guide management of the obese child. However, there is an ongoing discussion about how to define the MetS in childhood and adolescence. Since insulin resistance-the major driver of MetS-is influenced by pubertal stage, it is questionable to use definitions for MetS in children and adolescents that do not take into account pubertal status. A metabolic healthy status in prepubertal stage does not predict a metabolic healthy status during puberty. Furthermore, cardiovascular risk factors improve at the end of puberty without treatment. However, having a uniform internationally accepted definition of the MetS for children and adolescents would be very helpful for the description of populations in different studies. Therefore, the concept of MetS has to be revisited under the influence of puberty stage.

  9. 多囊卵巢综合征胰岛素抵抗新进展%Molecular Mechanism and Management in Insulin Resistance in Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    沈文娟; 匡洪影; 张跃辉

    2011-01-01

    Polycystic ovary syndrome (PCOS)is one of the most common endocrine disorder with a variety of clinical manifestations among women of reproductive age. Its features include chronic anovulation, multicystic morphology of ovaries,hyperandrogenism. In recent years,insulin resistance (IR)has been regarded as one of the mechanisms of the development of PCOS,and is also associated with the hyperandrogenemia and dysfunction of ovaries. Many researches have been done on the molecular mechanism of IR in PCOS,which might provide a theory foundation for the treatment. This review thus focuses on the molecular mechanism and treatment of insulin resistance in patients with PCOS.%多囊卵巢综合征(PCOS)是一种常见的影响育龄期女性生殖和内分泌功能的特殊疾病,其临床表现异质性,以慢性无排卵、卵巢多囊样改变、高雄激素血症为主要临床表现.胰岛素抵抗是其发生、发展的重要病理生理机制之一,也是导致高雄激素血症和卵巢功能改变的重要原因.近年来,PCOS患者胰岛素抵抗的分子机制得到深入研究,为临床治疗提供了理论依据.综述PCOS胰岛素抵抗的分子机制研究和药物治疗进展.

  10. High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance.

    LENUS (Irish Health Repository)

    O'Connor, A

    2010-03-01

    Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional\\/translational modification contributes to reduced HMW adiponectin in PCOS.

  11. Insulin Resistance Performance of Animal Models of Polycystic Ovary Syndrome%多囊卵巢综合征动物模型的胰岛素抵抗表现

    Institute of Scientific and Technical Information of China (English)

    杜丹峰; 李雪莲

    2013-01-01

    多囊卵巢综合征(PCOS)是育龄期妇女常见内分泌及代谢紊乱性疾病,病因不明,近年来越来越多的研究显示,高胰岛素血症和胰岛素抵抗在疾病发生发展过程中起到重要作用.进行疾病发生机制及治疗效果的研究通常应用动物模型,常见的多囊卵巢动物模型造模方法包括雄激素法、雄激素+人绒毛膜促性腺激素(hCG)法、雌激素法、来曲唑法、胰岛素+hCG法、孕激素+hCG法等.分析比较PCOS研究中常用的几种动物模型,探讨更适合研究胰岛素抵抗的动物模型.%Polycystic ovary syndrome (PCOS),whose etiology is still not clear,is a common endocrine disorder of reproductive-age female. More and more researches indicate that hyperinsulinemia and insulin resistance play an important role in the occurrence and development of PCOS in recent decades. Usually,we use a variety of animal models for the study of it's pathogenesis and therapeutic effect. Common polycystic ovary animal model manufacturing methods include androgen, andro-gen+hCG, estrogen method, letrozole method, insulin + hCG method, progesterone + hCG method, this paper summarizes the insulin resistance performance of common animal models of polycystic ovary syndrome , and to explore which model is more suitable for the study of insulin resistance in the occurrence and development of the disease.

  12. 胰岛素抵抗综合征的处理%Management of Insulin Resistance Syndrome

    Institute of Scientific and Technical Information of China (English)

    潘时中

    2000-01-01

    @@ 胰岛素抵抗(Insulin Resistance IR)综合征(Insulin Resistance Syndrome,IRS),是Reaven在1988年首次提出的X综合征(X Syndrome).它概括一系列与IR有关的代谢及生理紊乱,包括:胰岛素(Ins)刺激的葡萄糖摄取抵抗、高血糖、高胰岛素血症、高血压、冠心病、低密度脂蛋白血症、肥胖、高尿酸血症及脑血管意外等.它们具有一个共同的病理生理机制即IR.IR是指需要超常量的胰岛素才能引起正常量反应的一种状态,即机体胰岛素的靶组织器官(肝脏、肌肉、脂肪组织)对Ins的反应性敏感降低、受损或丧失而产生一系列病理变化和临床症状.因而机体为克服IR而引起代偿性高Ins血症.而高胰岛素血症又引起一系列病理过程即IRS, 又称CHAOS(Coronary heart disease, hypertension,hyperlipidemia, adult onset diabetes, obesity and stroke)综合征.高胰岛素血症是IR的一个主要标志.

  13. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  14. Stochastic simulations of normal aging and Werner's syndrome.

    KAUST Repository

    Qi, Qi

    2014-04-26

    Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner\\'s syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.

  15. Serum lipoprotein ratios as markers of insulin resistance: A study among non-diabetic acute coronary syndrome patients with impaired fasting glucose

    Directory of Open Access Journals (Sweden)

    S Ray

    2015-01-01

    Full Text Available Background & objectives: Recent data suggest that insulin resistance can predict cardiovascular disease independently of the other risk factors, such as hypertension, visceral obesity or dyslipidaemia. However, the majority of available methods to evaluate insulin resistance are complicated to operate, expensive, and time consuming. This study was undertaken to assess whether serum lipoprotein ratios could predict insulin resistance in non-diabetic acute coronary syndrome (ACS patients. Methods: Ninety non-diabetic patients with impaired fasting glucose admitted with a diagnosis of ACS were included in the study. At the time of admission fasting glucose and insulin concentrations were measured. The homeostatic model assessment-insulin resistance (HOMA-IR was used for insulin resistance. The fasting serum total cholesterol (TC, triglycerides (TG and high density lipoprotein cholesterol (HDL-C levels were checked, and then TC/HDL-C and TG/HDL-C ratios were calculated. The areas under the curves (AUC of the receiver operating characteristic (ROC curves were used to compare the power of these serum lipoprotein ratios as markers. Results: Lipoprotein ratios were significantly higher in patients with HOMA-IR index > 2.5 as compared to patients with index <2.5 (P < 0.05. Both TG/HDL-C and TC/HDL-C ratios were significantly correlated with HOMA-IR (P<0.05. The area under the ROC curve of the TG/HDL-C and TC/HDL-C ratio for predicting insulin resistance was 0.80 (95% CI, 0.67 to 0.93, 0.78 (95% CI, 0.65 to 0.91, respectively. Interpretation & conclusions: The findings of this study demonstrate that serum lipoprotein ratios can provide a simple means of identifying insulin resistance and can be used as markers of insulin resistance and cardiovascular diseases risk in adult non-diabetic patients.

  16. Specific suppression of insulin sensitivity in growth hormone receptor gene-disrupted (GHR-KO) mice attenuates phenotypic features of slow aging.

    Science.gov (United States)

    Arum, Oge; Boparai, Ravneet K; Saleh, Jamal K; Wang, Feiya; Dirks, Angela L; Turner, Jeremy G; Kopchick, John J; Liu, Jun-Li; Khardori, Romesh K; Bartke, Andrzej

    2014-12-01

    In addition to their extended lifespans, slow-aging growth hormone receptor/binding protein gene-disrupted (knockout) (GHR-KO) mice are hypoinsulinemic and highly sensitive to the action of insulin. It has been proposed that this insulin sensitivity is important for their longevity and increased healthspan. We tested whether this insulin sensitivity of the GHR-KO mouse is necessary for its retarded aging by abrogating that sensitivity with a transgenic alteration that improves development and secretory function of pancreatic β-cells by expressing Igf-1 under the rat insulin promoter 1 (RIP::IGF-1). The RIP::IGF-1 transgene increased circulating insulin content in GHR-KO mice, and thusly fully normalized their insulin sensitivity, without affecting the proliferation of any non-β-cell cell types. Multiple (nonsurvivorship) longevity-associated physiological and endocrinological characteristics of these mice (namely beneficial blood glucose regulatory control, altered metabolism, and preservation of memory capabilities) were partially or completely normalized, thus supporting the causal role of insulin sensitivity for the decelerated senescence of GHR-KO mice. We conclude that a delayed onset and/or decreased pace of aging can be hormonally regulated.

  17. Effect of pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    Hong-Wei Hao; Dong-Zhen Liu

    2015-01-01

    Objective: To analyze the effect of Pioglitazone combined with cyproterone acetate on the reproductive hormone level and insulin resistance of patients with polycystic ovary syndrome. Methods: 96 patients with the polycystic ovary syndrome in our hospital were randomly divided into observation group and controlgroup two groups, each of 48 cases. The control group was treated with the treatment of cyproterone acetate, observation group was treated with pioglitazone combined with cyproterone acetate treatment. The clinical efficacy of two groups were compared. The serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T) and fasting plasma glucose (FBG), fasting insulin (FINS) level before and after treatment and calculate the insulin resistance index (IR) were observed. Results: After treatment, serum FSH, LH and T levels of two groups were significantly lower than that before treatment (P0.05). FBG, FINS and IR of the patients in the observation group were significantly lower than the control group (P<0.05). Conclusion: pioglitazone combined with cyproterone acetate has significant therapeutic effect on polycystic ovary syndrome, can effectively improve the patients with insulin resistance and reproductive hormone disorder.

  18. Late-onset temperature reduction can retard the aging process in aged fish via a combined action of an anti-oxidant system and the insulin/insulin-like growth factor 1 signaling pathway.

    Science.gov (United States)

    Wang, Xia; Chang, Qingyun; Wang, Yu; Su, Feng; Zhang, Shicui

    2014-12-01

    Two different mechanisms are considered to be related to aging. Cumulative molecular damage caused by reactive oxygen species (ROS), the by-products of oxidative phosphorylation, is one of these mechanisms (ROS concept). Deregulated nutrient sensing by the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway is the second mechanism (IIS concept). Temperature reduction (TR) is known to modulate aging and prolong life span in a variety of organisms, but the mechanisms remain poorly defined. Here we first demonstrate that late-onset TR from 26 °C to 22 °C extends mean life span and maximum life span by approximately 5.2 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We then show that TR is able to decrease the accumulation of the histological aging markers senescence-associated β-galactosidase (SA-β-Gal) in the epithelium and lipofuscin (LF) in the liver and to reduce protein oxidation and lipid peroxidation levels in the muscle. We also show that TR can enhance the activities of catalase, glutathione peroxidase, and superoxide dismutase, and stimulate the synthesis of SirT1 and FOXO3A/FOXO1A, both of which are the downstream regulators of the IIS pathway. Taken together, our findings suggest that late-onset TR, a simple non-intrusion intervention, can retard the aging process in aged fish, resulting in their life span extension, via a synergistic action of an anti-oxidant system and the IIS pathway. This also suggests that combined assessment of the ROS and IIS concepts will contribute to providing a more comprehensive view of the anti-aging process.

  19. Association of adiponectin gene polymorphism with adiponectin levels and risk for insulin resistance syndrome

    Directory of Open Access Journals (Sweden)

    Jai Prakash

    2015-01-01

    Conclusions: We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome.

  20. Shift work aggravates metabolic syndrome development among early-middle-aged males with elevated ALT

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Lin; Tun-Jen Hsiao; Pau-Chung Chen

    2009-01-01

    AIM: To examine whether shift work accelerates metabolic syndrome (MetS) development among early middle- aged males with elevated alanine aminotransferase (e-ALT).METHODS: A retrospective, observational followup study on MetS development at a 5-year interval was conducted using health examination data. Nine hundred and ninety six male employees not fulfilling MetS criteria at screening were enrolled. Age, MetScomponents,liver enzymes, serological markers for viral hepatitis, abdominal ultrasound, insulin resistance status, lifestyles, and workplace factors were analyzed.RESULTS: The prevalence of elevated serum ALT (> 40 U/L, e-ALT) at baseline was 19.1%. There were 381 (38.3%) workers with long-term exposures to daynight rotating shift work (RSW). 14.2% of subjects developed MetS during follow-up. After 5 years, the workers with e-ALT had significantly unfavorable changes in MetS-components, and higher rates of MetS development, vs subjects with normal baseline ALT levels. Workers with both baseline e-ALT and 5-year persistent RSW (pRSW) exposure had the highest rate of MetS development. Also, e-ALT-plus-pRSW workers had a significant increase in MetS-components at follow-up, compared with the other subgroups. After controlling for potential confounders, e-ALT-plus-pRSW workers posed a significant risk for MetS development (odds ratio, 2.7; 95% confidence interval, 1.4-5.3, vs workers without baseline e-ALT nor pRSW). CONCLUSION: We suggest that all early middleaged male employees with e-ALT should be evaluated and managed for MetS. Particularly in terms of job arrangements, impacts of long-term RSW on MetS development should be assessed for all male employees having baseline e-ALT.

  1. Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS).

    Science.gov (United States)

    Hurliman, Amanda; Keller Brown, Jennifer; Maille, Nicole; Mandala, Maurizio; Casson, Peter; Osol, George

    2015-11-01

    This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

  2. Study on the Relationship between Insulin-Resistance and Syndrome Differentiation Typing in Hypertension Patients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    [1]Reaven GM. Role of insulin resistance in human disease. Diabetes, 1988, 37∶1595.[2]CHEN HZ, edit. Practical Internal Medicine (10th edition) Beijing: People's Healthing Publishing House 1997∶1283.[3]Guidance on Principle of Clinical Research of Chinese New Drugs (trial). Vol.1.1993∶28 ( promulgated by Ministry of Health, PRC).[4]LI GW, PAN RR, Lillioja, et al., A new index of determining insulin-sensitivity among people. J Chin Internal Medicine 1993:32(11)∶656.[5]Suislocri A. Insulin resistance and hypertension. Am J Med Sci 1990;300∶104.[6]Kannel WB, Wilson WF, ZHENG TJ. The epidemiology of impaired glucose tolerance and hypertension. Am Heart J 1991;121∶1268-1273.[7]LIU GZ, GAO RL, LI GW, et al. Summary of National Meetings on Hypertension, Coronary Heart Diseases and Diabetes. J China Cardiovascular Diseases 1993;21(4)∶260.

  3. Aegle marmelos (L.) Corr. impedes onset of Insulin resistance syndrome in rats provided with drinking fructose from weaning to adulthood stages of development: A mechanistic study.

    Science.gov (United States)

    Mathur, Rajani; Sehgal, Ratika; Rajora, Preeti; Sharma, Shveta; Kumar, Rajesh; Mathur, Sandeep

    2016-12-17

    To explore the effect of aqueous extract of leaves of Aegle marmelos (AM) on hepatic carbohydrate metabolism and insulin downstream signalling in rats provided with drinking fructose (15%) from weaning to adulthood. Wistar albino rats (4week) were randomly divided into Normal Control (NC), Fructose Control (FC) and treatment (AMT) groups and provided over 8 weeks, chow + water, chow + fructose (15%) and chow + fructose (15%) + AM (500 mg/kg/d, p.o.), respectively. Significantly (pInsulin Resistance Syndrome (IRS) is delineated here, along with the potential of Aegle marmelos in impeding the same.

  4. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome.

    Science.gov (United States)

    Buhl, Esben S; Jessen, Niels; Pold, Rasmus; Ledet, Thomas; Flyvbjerg, Allan; Pedersen, Steen B; Pedersen, Oluf; Schmitz, Ole; Lund, Sten

    2002-07-01

    The insulin resistance syndrome is characterized by several risk factors for cardiovascular disease. Chronic chemical activation of AMP-activated protein kinase by the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta -D-ribofuranoside (AICAR) has been shown to augment insulin action, upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic clamp conditions. To investigate whether chronic AICAR administration, in addition to the beneficial effects on insulin sensitivity, is capable of improving other phenotypes associated with the insulin resistance syndrome, obese Zucker (fa/fa) rats (n = 6) exhibiting insulin resistance, hyperlipidemia, and hypertension were subcutaneously injected with AICAR (0.5 mg/g body wt) daily for 7 weeks. Obese control rats were either pair-fed (PF) (n = 6) or ad libitum-fed (AL) (n = 6). Lean Zucker rats (fa/-) (n = 8) served as a reference group. AICAR administration significantly reduced plasma triglyceride levels (P < 0.01 for AICAR vs. AL, and P = 0.05 for AICAR vs. PF) and free fatty acids (P < 0.01 for AICAR vs. AL, and P < 0.05 for AICAR vs. PF) and increased HDL cholesterol levels (P < 0.01 for AICAR vs. AL and PF). AICAR treatment also lowered systolic blood pressure by 14.6 +/- 4.3 mmHg (P < 0.05), and AICAR-treated animals exhibited a tendency toward decreased intra-abdominal fat content. Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals. Finally, in line with previous findings, AICAR treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles. Our

  5. Metabolic Syndrome

    Science.gov (United States)

    ... hypertension, hypertriglyceridemia, insulin resistance syndrome, low HDL cholesterol, Metabolic Syndrome, overweight, syndrome x, type 2 diabetes Family Health, Kids and Teens, Men, Women January 2005 Copyright © American Academy of Family PhysiciansThis ...

  6. Androgen receptor roles in insulin resistance and obesity in males: the linkage of androgen-deprivation therapy to metabolic syndrome.

    Science.gov (United States)

    Yu, I-Chen; Lin, Hung-Yun; Sparks, Janet D; Yeh, Shuyuan; Chang, Chawnshang

    2014-10-01

    Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men. Androgen-deprivation therapy (ADT) is the first-line treatment and fundamental management for men with advanced PCa to suppress functions of androgen/androgen receptor (AR) signaling. ADT is effective at improving cancer symptoms and prolonging survival. However, epidemiological and clinical studies support the notion that testosterone deficiency in men leads to the development of metabolic syndrome that increases cardiovascular disease risk. The underlying mechanisms by which androgen/AR signaling regulates metabolic homeostasis in men are complex, and in this review, we discuss molecular mechanisms mediated by AR signaling that link ADT to metabolic syndrome. Results derived from various AR knockout mouse models reveal tissue-specific AR signaling that is involved in regulation of metabolism. These data suggest that steps be taken early to manage metabolic complications associated with PCa patients receiving ADT, which could be accomplished using tissue-selective modulation of AR signaling and by treatment with insulin-sensitizing agents.

  7. Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome.

    Science.gov (United States)

    Scott, David; Joham, Anju; Teede, Helena; Gibson-Helm, Melanie; Harrison, Cheryce; Cassar, Samantha; Hutchison, Samantha; Ebeling, Peter R; Stepto, Nigel; de Courten, Barbora

    2016-11-30

    Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m²). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m²/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women.

  8. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

    Science.gov (United States)

    Sistrun, Sakita N.; Morel, Kelley S.; Nestler, John E.

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n = 16) and normal (n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUCDCI-IPG), AUCinsulin, and AUCDCI-IPG/AUCinsulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUCDCI-IPG/AUCinsulin at baseline and a significant relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (−4.08 kg) and normal women (−4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUCDCI-IPG/AUCinsulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  9. Evaluation of Oxidative Stress in Women with Polycystic Ovarian Syndrome as Represented by Serum Ischemia Modified Albumin and Its Correlation with Testosterone and Insulin Resistance.

    Science.gov (United States)

    Beyazit, Fatma; Yilmaz, Nafiye; Balci, Osman; Adam, Magdi; Yaman, Selen Taflan

    2016-01-01

    Objective Ischemia-mediated oxidative stress and inflammation have been reported to be important contributors to the pathogenesis of polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) is a novel marker generated under ischemic and oxidative conditions and may reflect disease activity in distinct disease states. Therefore, we investigated whether the serum IMA levels are affected in infertile PCOS patients. Methods Forty-six patients with infertile PCOS, 30 patients with unexplained infertility, and 31 age- and body mass index (BMI)-matched controls were included in this cross-sectional study. Biochemical parameters, serum IMA levels, and their correlations with serum testosterone and insulin resistance were determined for each subject. Results In patients with infertile PCOS, the serum IMA levels were significantly elevated (p=0.003) compared with unexplained infertility patients and controls. A correlation analysis suggested that the IMA levels only correlated with the serum free testosterone levels in PCOS patients (r=0.43, p=0.028). Conclusion Elevations in the serum IMA levels in infertile PCOS patients may suggest a possible additional role of oxidative stress mechanisms in disease pathophysiology. Moreover, correlation between serum IMA and testosterone levels may influence the quality of oocytes via alterations in the balance of critical follicular fluid factors in the follicular microenvironment.

  10. Activation of α7 nicotinic acetylcholine receptor decreases on-site mortality in crush syndrome through insulin signaling-Na/K-ATPase pathway

    Directory of Open Access Journals (Sweden)

    Bo-Shi eFan

    2016-03-01

    Full Text Available On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with anisodamine decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with anisodamine (20 mg/kg and 28 mg/kg respectively, i.p. 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist and PNU282987 (selective α7nAChR agonist, or in α7nAChR knockout mice. Effect of anisodamine was also appraised in C2C12 myotubes. Anisodamine reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by anisodamine. Phosphorylation of Na/K-ATPase was enhanced by anisodamine in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of anisodamine on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway.

  11. Model of human aging: Recent findings on Werner’s and Hutchinson-Gilford progeria syndromes

    Directory of Open Access Journals (Sweden)

    Shian-ling Ding

    2008-09-01

    Full Text Available Shian-ling Ding1, Chen-Yang Shen2,3,41Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan; 2Institute of Biomedical Sciences, and 3Life Science Library, Academia Sinica, Taipei, Taiwan; 4Graduate Institute of Environmental Science, China Medical University, Taichong, TaiwanAbstract: The molecular mechanisms involved in human aging are complicated. Two progeria syndromes, Werner’s syndrome (WS and Hutchinson-Gilford progeria syndrome (HGPS, characterized by clinical features mimicking physiological aging at an early age, provide insights into the mechanisms of natural aging. Based on recent findings on WS and HGPS, we suggest a model of human aging. Human aging can be triggered by two main mechanisms, telomere shortening and DNA damage. In telomere-dependent aging, telomere shortening and dysfunction may lead to DNA damage responses which induce cellular senescence. In DNA damage-initiated aging, DNA damage accumulates, along with DNA repair deficiencies, resulting in genomic instability and accelerated cellular senescence. In addition, aging due to both mechanisms (DNA damage and telomere shortening is strongly dependent on p53 status. These two mechanisms can also act cooperatively to increase the overall level of genomic instability, triggering the onset of human aging phenotypes.Keywords: human aging, Hutchinson-Gilford Progeria syndrome, Werner syndrome

  12. Zinc, Iron and Vitamins A, C and E Are Associated with Obesity, Inflammation, Lipid Profile and Insulin Resistance in Mexican School-Aged Children

    OpenAIRE

    Olga Patricia García; Dolores Ronquillo; María del Carmen Caamaño; Guadalupe Martínez; Mariela Camacho; Viridiana López; Jorge L. Rosado

    2013-01-01

    The objective of this cross-sectional study was to evaluate the relationship between micronutrient status and obesity, lipids, insulin resistance and chronic inflammation in children. Weight, height, waist circumference and body composition (dual-energy X-ray absorptiometry (DEXA)) were determined in 197 school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP), zinc, iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin E:lipids were negatively associated ...

  13. Association of age at menarche with metabolic syndrome and its components in rural Bangladeshi women

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    Akter Shamima

    2012-11-01

    Full Text Available Abstract Background Early age at menarche is associated with increased risk of metabolic syndrome in both China and the West. However, little is known about the impact of age at menarche and metabolic syndrome in South Asian women, including those from low-income country, where age at menarche is also falling. The aim of the present study was to investigate whether age at menarche is inversely associated with metabolic syndrome in Bangladeshi women, who are mostly poor and have limited access to and or poor health care facilities. Methods This community-based cross-sectional study was performed using 1423 women aged between 15–75 years from rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between age at menarche and metabolic syndrome, with adjustment of potential confounding variables, including age, education, marital status, tobacco users, use of contraceptives and number of pregnancies. Results Early onset of menarche (13 years was found to be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95 % confidence interval =1.05-2.30. Age at onset of menarche was also inversely associated with prevalence of high triglycerides (P for trend P for trend = 0.01, but positively associated with prevalence of high fasting blood glucose (P for trend =0.02. However, no significant association was found between age at menarche, high blood pressure and elevated waist circumference. Conclusion Early onset of menarche might promote or trigger development of metabolic syndrome. Thus, knowledge of the history of age at onset of menarche may be critical in identifying women at risk of developing metabolic syndrome and those likely to benefit the most from early interventions.

  14. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome.

    Science.gov (United States)

    Melnik, Bodo C; John, Swen Malte; Schmitz, Gerd

    2011-06-24

    The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet.

  15. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome

    Directory of Open Access Journals (Sweden)

    Schmitz Gerd

    2011-06-01

    Full Text Available Abstract The insulin/insulin-like growth factor-1 (IGF-1 pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet.

  16. Prevalence of metabolic syndrome in adolescents aged 10-18 years in Jammu, J and K

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    Narinder Singh

    2013-01-01

    Full Text Available Objective: To estimate the prevalence of metabolic syndrome among adolescents attending school in the Jammu region, India. Materials and Methods: This is a cross-sectional study conducted between November 2009 and December 2010, among a total of 1160 school-going adolescents of both sexes aged 10-18 years. Relevant metabolic and anthropometric variables were analyzed and criteria suggested by National Cholesterol Education Program Adult Treatment Panel Third (NCEP-ATP III modified for age was used to define metabolic syndrome. Results: The overall prevalence of metabolic syndrome was 2.6%. Prevalence of metabolic syndrome was higher in males (3.84% than in females (1.6% and slightly higher in urban area (2.80% than in rural area (2.52%, whereas prevalence of metabolic syndrome among centrally obese subjects was as high as 33.33%. High density lipoprotein cholesterol was the most common and high blood pressure was the least common constituent of metabolic syndrome. Metabolic syndrome was most prevalent in 16-18 years age group (4.79%. Conclusion : This study demonstrates that metabolic syndrome phenotype exists in substantial number (up to 3% of adolescent population in the Jammu region, India, and particularly 33% of obese adolescents are at risk to develop metabolic syndrome. These findings pose a serious threat to the current and future health of these young people.

  17. Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood

    Science.gov (United States)

    Polycystic ovary syndrome (PCOS) is a prevalent hyperandrogenic infertility and cardiometabolic disorder that increases a woman's lifetime risk of type 2 diabetes mellitus. It is heritable and intensely familial. Progress toward a cure has been delayed by absence of an etiology. Evidence is mounting...

  18. The diagnostic value of the EEG in Angelman and Rett syndrome at a young age

    NARCIS (Netherlands)

    Laan, LAEM; Brouwer, OF; Begeer, CH; Zwinderman, AH; van Dijk, JG

    1998-01-01

    We determined the diagnostic value of the EEG in young children with Angelman syndrome (AS) and Rett syndrome (RS). EEGs, recorded before 5 years of age, of 10 patients with AS, 10 with RS and 10 with mental retardation of other origin were studied blindly by two examiners for the presence of the fo

  19. Metabolic syndrome in women of childbearing age and pregnancy: recognition and management of dyslipidemia.

    Science.gov (United States)

    Paramsothy, Pathmaja; Knopp, Robert H

    2005-01-01

    The obesity pandemic engenders the global threat of metabolic syndrome and its related disorders, including diabetes and coronary artery disease (CAD). The purpose of this review is to discuss the deleterious effects of metabolic syndrome on women of childbearing age, including pregnancy, with a discussion of lipid management. Treatment options will also be presented.

  20. Developmental Trajectories of Structural and Pragmatic Language Skills in School-Aged Children with Williams Syndrome

    Science.gov (United States)

    Van Den Heuvel, E.; Manders, E.; Swillen, A.; Zink, I.

    2016-01-01

    Background: This study aimed to compare developmental courses of structural and pragmatic language skills in school-aged children with Williams syndrome (WS) and children with idiopathic intellectual disability (IID). Comparison of these language trajectories could highlight syndrome-specific developmental features. Method: Twelve monolingual…

  1. Effect of maternal dietary counselling during the 1st year of life on glucose profile and insulin resistance at the age of 8 years: a randomised field trial.

    Science.gov (United States)

    Costa, Cintia S; Campagnolo, Paula D B; Lumey, L H; Vitolo, Marcia R

    2017-01-01

    Education interventions that stimulate complementary feeding practices can improve the nutritional status of children and may protect against future chronic diseases. We assessed the long-term effectiveness of dietary intervention during the 1st year of life on insulin resistance levels, and investigated the relationship between insulin resistance and weight changes over time. A randomised field trial was conducted among 500 mothers who gave birth to full-term infants between October 2001 and June 2002 in a low-income area in São Leopoldo, Brazil. Mother-child pairs were randomly assigned to intervention (n 200) and control groups (n 300), and the mothers in the intervention group received dietary counselling on breast-feeding and complementary feeding of their children during the 1st year of life. Fieldworkers blinded to assignment assessed socio-demographic, dietary and anthropometric data during follow-up at ages 1, 4 and 8 years. Blood tests were performed in 305 children aged 8 years to measure fasting serum glucose and insulin concentrations and the homoeostasis model assessment index of insulin resistance (HOMA-IR). At the age of 8 years, the intervention group showed no changes in glucose and insulin concentrations or HOMA-IR values (change 0·07; 95 % CI -0·06, 0·21 for girls; and change -0·07; 95 % CI -0·19, 0·04 for boys) compared with study controls. Insulin resistance was highly correlated, however, with increases in BMI between birth and 8 years of age. Although this dietary intervention had no impact on glucose profile at age 8 years, our findings suggest that BMI changes in early childhood can serve as an effective marker of insulin resistance.

  2. Infants with Down Syndrome: Percentage and Age for Acquisition of Gross Motor Skills

    Science.gov (United States)

    Pereira, Karina; Basso, Renata Pedrolongo; Lindquist, Ana Raquel Rodrigues; da Silva, Louise Gracelli Pereira; Tudella, Eloisa

    2013-01-01

    The literature is bereft of information about the age at which infants with Down syndrome (DS) acquire motor skills and the percentage of infants that do so by the age of 12 months. Therefore, it is necessary to identify the difference in age, in relation to typical infants, at which motor skills were acquired and the percentage of infants with DS…

  3. Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome.

    Science.gov (United States)

    Romero-Aleshire, Melissa J; Diamond-Stanic, Maggie K; Hasty, Alyssa H; Hoyer, Patricia B; Brooks, Heddwen L

    2009-09-01

    Factors comprising the metabolic syndrome occur with increased incidence in postmenopausal women. To investigate the effects of ovarian failure on the progression of the metabolic syndrome, female B(6)C(3)F(1) mice were treated with 4-vinylcyclohexene diepoxide (VCD) and fed a high-fat (HF) diet for 16 wk. VCD destroys preantral follicles, causing early ovarian failure and is a well-characterized model for the gradual onset of menopause. After 12 wk on a HF diet, VCD-treated mice had developed an impaired glucose tolerance, whereas cycling controls were unaffected [12 wk AUC HF mice 13,455 +/- 643 vs. HF/VCD 17,378 +/- 1140 mg/dl/min, P diet, VCD-treated mice had significantly higher fasting insulin levels (HF 5.4 +/- 1.3 vs. HF/VCD 10.1 +/- 1.4 ng/ml, P diet (HF 56.2 +/- 16.7 vs. HF/VCD 113.1 +/- 19.6 mg/dl x microU/ml, P diet gained more weight than mice on a standard diet, and weight gain in HF/VCD mice was significantly increased compared with HF cycling controls. Interestingly, even without a HF diet, progression into VCD-induced menopause caused a significant increase in cholesterol and free fatty acids. Furthermore, in mice fed a standard diet (6% fat), insulin resistance developed 4 mo after VCD-induced ovarian failure. Insulin resistance following ovarian failure (menopause) was prevented by estrogen replacement. Studies here demonstrate that ovarian failure (menopause) accelerates progression into the metabolic syndrome and that estrogen replacement prevents the onset of insulin resistance in VCD-treated mice. Thus, the VCD model of menopause provides a physiologically relevant means of studying how sex hormones influence the progression of the metabolic syndrome.

  4. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    OpenAIRE

    Maria Jose Sáez-Lara; Candido Robles-Sanchez; Francisco Javier Ruiz-Ojeda; Julio Plaza-Diaz; Angel Gil

    2016-01-01

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non...

  5. Serum 25(OHD is inversely associated with metabolic syndrome risk profile among urban middle-aged Chinese population

    Directory of Open Access Journals (Sweden)

    Yin Xiao

    2012-09-01

    Full Text Available Abstract Background Vitamin D deficiency is associated with a variety of chronic metabolic diseases. Limited evidence regarding vitamin D deficiency exists within the Chinese population. The present study aims to examine the association between serum vitamin D concentrations and cardiometabolic risk factors in the young and middle-aged, urban Chinese population Methods The cross-sectional relationships between serum 25-hydroxyvitamin D [25(OHD] concentrations and indices of adiposity and cardiometabolic risk factors (e.g., body mass index, waist circumference, fasting plasma glucose, etc. were evaluated in 601 non-diabetic adults. Result Vitamin D deficiency or insufficiency was present in 66% of the tested population, and serum 25(OHD levels were lower in patients who were overweight/obese or suffered metabolic syndrome when compared to individuals of healthy weight without metabolic syndrome (24.08 ± 8.08 vs 31.70 ± 11.77 ng/ml, 21.52 ± 6.9 vs 31.74 ± 10.21 ng/ml respectively. 25(OHD was inversely associated with waist circumference, fasting glucose, fasting insulin, triglycerides and LDL-cholesterol, and it was positively associated with HDL-cholesterol in a multivariable-adjusted regression model. Conclusion Vitamin D deficiency is common in the young and middle-aged, urban Chinese population, with high prevalence in overweight/obese individuals and patients with metabolic syndrome. Low vitamin D concentration was associated with indices of adiposity and cardiometabolic risk factors. Further studies are warranted to elucidate the cause-effect relation between vitamin D status, obesity and related metabolic disorders. Trial registration Current Controlled Trials (ISRCTN21527585

  6. EEG features of absence seizures in idiopathic generalized epilepsy: Impact of syndrome, age, and state

    DEFF Research Database (Denmark)

    Sadleir, L.G.; Scheffer, I.E.; Smith, S.

    2009-01-01

    Purpose: Factors influencing the electroencephalography (EEG) features of absence seizures in newly presenting children with idiopathic generalized epilepsy (IGE) have not been rigorously studied. We examined how specific factors such as state, provocation, age, and epilepsy syndrome affect the E...

  7. Mitigation of Insulin Resistance by Mangiferin in a Rat Model of Fructose-Induced Metabolic Syndrome Is Associated with Modulation of CD36 Redistribution in the Skeletal Muscle.

    Science.gov (United States)

    Zhou, Liang; Pan, Yongquan; Chonan, Ritsu; Batey, Robert; Rong, Xianglu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

    2016-01-01

    Mangiferin is one of the prominent active components responsible for the antidiabetic property of many traditional herbs, but its underlying mechanisms of action remain unclear. CD36 in skeletal muscle is known to contribute to the etiology of insulin resistance by facilitating fatty acid uptake. This study investigated the effect of mangiferin on insulin resistance. The results showed that treatment of Wistar-Kyoto rats with mangiferin (15 mg/kg, once daily, by oral gavage) for 7 weeks inhibited chronic liquid fructose consumption-induced increases in plasma insulin concentrations at the baseline and during oral glucose tolerance test (OGTT), and the homeostasis model assessment of insulin resistance index. It also suppressed the increases in fasted plasma nonesterified fatty acid (NEFA) concentration and the adipose tissue insulin resistance index. Mechanistically, mangiferin neither affected intakes of fructose and chow, and the increase in epididymal and perirenal fat, nor attenuated fructose-induced hypertension. In contrast, mangiferin attenuated fructose-induced acceleration of plasma NEFA clearance during OGTT, and tended to decrease excessive triglyceride accumulation in gastrocnemius. Immunofluorescence staining and subsequent rating of CD36-expressing fibers in gastrocnemius revealed that mangiferin restored fructose-stimulated sarcolemmal CD36 overexpression and decreased intracellular CD36 distribution. In addition, the effects of mangiferin on the parameters associated with insulin resistance and abnormal fatty acid metabolism were absent in the spontaneously hypertensive rats carrying numerous nonfunctional mutations in the CD36 gene. Thus, these results suggest that mangiferin treatment mitigates insulin resistance in a rat model of fructose-induced metabolic syndrome by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle.

  8. Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.

    Science.gov (United States)

    Wagenmakers, Anton J M; Strauss, Juliette A; Shepherd, Sam O; Keske, Michelle A; Cocks, Matthew

    2016-04-15

    This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres.

  9. Zinc, iron and vitamins A, C and e are associated with obesity, inflammation, lipid profile and insulin resistance in Mexican school-aged children.

    Science.gov (United States)

    García, Olga Patricia; Ronquillo, Dolores; del Carmen Caamaño, María; Martínez, Guadalupe; Camacho, Mariela; López, Viridiana; Rosado, Jorge L

    2013-12-10

    The objective of this cross-sectional study was to evaluate the relationship between micronutrient status and obesity, lipids, insulin resistance and chronic inflammation in children. Weight, height, waist circumference and body composition (dual-energy X-ray absorptiometry (DEXA)) were determined in 197 school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP), zinc, iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin E:lipids were negatively associated with Body Mass Index (BMI), waist-to-height ratio (WHR) and body and abdominal fat (p obese who also had low concentrations of vitamin A had higher CRP and lower triglycerides (p zinc concentrations had higher insulin resistance compared with children with adequate weight (p obesity. Furthermore, low concentrations of zinc, vitamins A and E in children who were overweight and obese were associated with lipids, inflammation and insulin resistance.

  10. Metabolic syndrome

    Science.gov (United States)

    ... obesity ). This body type may be described as "apple-shaped." Insulin resistance. Insulin is a hormone produced ... Syndrome Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the ...

  11. Elevated estimated arterial age is associated with metabolic syndrome and low-grade inflammation

    DEFF Research Database (Denmark)

    Greve, Sara V; Blicher, Marie K; Kruger, Ruan

    2016-01-01

    BACKGROUND: Arterial age can be estimated from equations relating arterial stiffness to age and blood pressure in large cohorts. We investigated whether estimated arterial age (eAA) was elevated in patients with the metabolic syndrome and/or known cardiovascular disease (CVD), which factors were...... of metabolic syndrome, Systematic COronary Risk Evaluation, or Framingham risk score. From age, mean blood pressure, and cfPWV, eAA and estimated cfPWV (ePWV) were calculated. In 2006, the combined cardiovascular endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke...

  12. A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17A1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome

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    Ushasi Banerjee

    2016-01-01

    Full Text Available Background & objectives: Insulin resistance (IR is a major confounding factor in polycystic ovarian syndrome (PCOS irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. Methods: Polymorphism study was performed by restriction fragment length polymorphism (RFLP analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women. Serum testosterone, BMI and HOMA-IR (homeostatic model of assessment-insulin resistance were analyzed by standard techniques. A realistic cut-off value for the HOMA-IR was obtained through receiver operating characteristic (ROC curve for exploring any possible link between IR and T/C polymorphism in the case group. Results: Significant increases in serum testosterone and HOMA-IR values were observed among the case group (P<0.001 without any significant elevation in BMI and FBG compared to controls. Cut-off value for IR in the PCOS patients was 1.40 against a maximum sensitivity of 0.83 and a minimum false positivity of 0.13. The analysis revealed an inconclusive link between the C/T polymorphic distribution and insulin resistant case subjects. Interpretation & conclusions: The results showed that CYP17A1 gene was not conclusively linked to either IR or its associated increased androgen secretion in non-obese women with PCOS. We propose that an increased sensitivity of insulin on the ovarian cells may be the predominant reason for the clinical effects and symptoms of androgen excess observed in non-obese PCOS patients in our region.

  13. Chronic TNF-a neutralization does not improve insulin resistance or endothelial function in "healthy" men with metabolic syndrome

    NARCIS (Netherlands)

    Wascher, T.C.; Lindeman, J.H.N.; Sourij, H.; Kooistra, T.; Pacini, G.; Roden, M.

    2011-01-01

    The possible contribution of tumor necrosis factor-a (TNF-a) to the development of obesity associated insulin resistance in humans is still controversial. Our study investigated the effect of TNF-a neutralization on insulin resistance in healthy, obese and insulin resistant men. We performed a prosp

  14. Sensitive and specific markers for insulin resistance, hyperandrogenemia, and inappropriate gonadotrophin secretion in women with polycystic ovary syndrome: a case-control study from Bahrain

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    Al-Ayadhi MA

    2012-05-01

    Full Text Available Jamal Golbahar,1,2,* Maha Al-Ayadhi,2,* Negalla Mohan Das,2 Khalid Gumaa,2 1Department of Molecular Medicine, Al-Jawhara Centre for Genetic Diagnosis and Research, 2Department of Medical Biochemistry, College of Medicine and Medical Sciences, AGU, Manama, Bahrain *These authors contributed equally to this articleBackground: In women with polycystic ovary syndrome (PCOS, despite a high prevalence of insulin resistance, hyperandrogenemia, and disturbances in the secretion of gonadotrophin, the principal causes of biochemical abnormalities and the best endocrine markers for PCOS have not been fully identified.Subjects and methods: Serum levels of insulin, glucose, follicle-stimulating hormone (FSH, luteinizing hormone (LH, total testosterone, estrogen, sex hormone-binding capacity (SHBG, and other related indices such as homeostasis model assessment, insulin glucose ratios, LH/FSH ratios, and the free androgen index (FAI were determined and compared in women with PCOS (n = 50 and women without PCOS (n = 50.Results: In multivariate logistic regression analyses, among all insulin resistance indices, only hyperinsulinemia (odds ratio [OR] = 2.6; confidence interval [CI]: 1.3–5.2; P = 0.008 was significantly and independently associated with PCOS when adjusted for body mass index (BMI, hyperandrogenemia, and LH/FSH ratios. The LH/FSH ratio (OR = 5.4; CI: 1.2–23.0, P = 0.03 was the only marker among those indices for inappropriate gonadotrophin secretion that significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. Among those indices for hyperandrogenemia, FAI (OR = 1.1; CI: 1.0–2.7; P = 0.02 and SHBG (OR = 1.2; CI: 1.2–3.4; P = 0.03 were significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. In addition, receiver operating characteristic analysis showed that the best predictive markers for PCOS were insulin (area under the curve [AUC] = 0.944; CI: 0.887–0

  15. Eating habits of preschool children and the risk of obesity, insulin resistance and metabolic syndrome in adults.

    Science.gov (United States)

    Kostecka, Małgorzata

    2014-01-01

    Background & Objective : Nutrient excess and nutrient deficiency in the diets of preschool children can lead to permanent modification of metabolic pathways and increased risk of diet-dependent diseases in adults. Children are most susceptible to the adverse consequences of bad eating habits.The objective of this study was to evaluate the eating habits and the diets of preschool children as risk factors for excessive weight, obesity, insulin resistance and the metabolic syndrome. Methods : The study was conducted on 350 randomly selected preschool children attending kindergartens in south-eastern Poland. Three-day dietary recalls were processed and evaluated in the Dieta 5 application. Results : The analyzed diets were characterized by low diversity and a high share of processed foods, such as pate, sausages, ketchup, mayonnaise, fried meat, French fries and fast-food. The dietary content of vegetables, raw fruit, dairy products and whole grain products was alarmingly low. Conclusions : Diets characterized by excessive energy value and nutritional deficiency can lead to health problems. In most cases, excessive weight gain in children can be blamed on parents and caretakers who are not aware of the health consequences of high-calorie foods rich in fats and sugar.

  16. Treatment of Refractory Postural Tachycardia Syndrome with Subcutaneous Octreotide Delivered Using an Insulin Pump

    Directory of Open Access Journals (Sweden)

    Muhammad Khan

    2015-01-01

    Full Text Available Postural Tachycardia Syndrome (PoTS represents a disorder of the autonomic nervous system that results in symptoms of orthostatic intolerance. Despite having a severe impact on the patient’s quality of life, the current treatment options for PoTS are based on limited evidence. Subsequently, this results in clinicians having to utilise a variety of treatment regimens in the hope of successfully providing symptomatic relief. However, the options available for PoTS are not without significant side effects that can worsen an already debilitating condition. Our cases provide a further novel treatment option for clinicians to consider in PoTS refractory to established treatments.

  17. Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

    Directory of Open Access Journals (Sweden)

    C.A. Mourão-Júnior

    2006-04-01

    Full Text Available Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI, waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001 after the addition of metformin (1404.4 ± 565.5 mg/day, with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05 of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL, BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m², waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm, and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01% and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

  18. The Effects of Calcium, Vitamins D and K co-Supplementation on Markers of Insulin Metabolism and Lipid Profiles in Vitamin D-Deficient Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Karamali, Maryam; Ashrafi, Mahnaz; Razavi, Maryamalsadat; Jamilian, Mehri; Kashanian, Maryam; Akbari, Maryam; Asemi, Zatollah

    2017-04-13

    Data on the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles among vitamin D-deficient women with polycystic ovary syndrome (PCOS) are scarce. This study was done to determine the effects of calcium, vitamins D and K co-supplementation on markers of insulin metabolism and lipid profiles in vitamin D-deficient women with PCOS. This randomized double-blind, placebo-controlled trial was conducted among 55 vitamin D-deficient women diagnosed with PCOS aged 18-40 years old. Subjects were randomly assigned into 2 groups to intake either 500 mg calcium, 200 IU vitamin D and 90 µg vitamin K supplements (n=28) or placebo (n=27) twice a day for 8 weeks. After the 8-week intervention, compared with the placebo, joint calcium, vitamins D and K supplementation resulted in significant decreases in serum insulin concentrations (-1.9±3.5 vs. +1.8±6.6 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-0.4±0.7 vs. +0.4±1.4, P=0.01), homeostasis model of assessment-estimated b cell function (-7.9±14.7 vs. +7.0±30.3, P=0.02) and a significant increase in quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.008±0.03, P=0.01). In addition, significant decreases in serum triglycerides (-23.4±71.3 vs. +9.9±39.5 mg/dL, P=0.03) and VLDL-cholesterol levels (-4.7±14.3 vs. +2.0±7.9 mg/dL, P=0.03) was observed following supplementation with combined calcium, vitamins D and K compared with the placebo. Overall, calcium, vitamins D and K co-supplementation for 8 weeks among vitamin D-deficient women with PCOS had beneficial effects on markers of insulin metabolism, serum triglycerides and VLDL-cholesterol levels.

  19. Plasma BDNF Is Reduced among Middle-Aged and Elderly Women with Impaired Insulin Function: Evidence of a Compensatory Mechanism

    Science.gov (United States)

    Arentoft, Alyssa; Sweat, Victoria; Starr, Vanessa; Oliver, Stephen; Hassenstab, Jason; Bruehl, Hannah; Tirsi, Aziz; Javier, Elizabeth; McHugh, Pauline F.; Convit, Antonio

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to…

  20. The immune-endocrine loop during aging: role of growth hormone and insulin-like growth factor-I.

    Science.gov (United States)

    Burgess, W; Liu, Q; Zhou, J; Tang, Q; Ozawa, A; VanHoy, R; Arkins, S; Dantzer, R; Kelley, K W

    1999-01-01

    Why a primary lymphoid organ such as the thymus involutes during aging remains a fundamental question in immunology. Aging is associated with a decrease in plasma growth hormone (somatotropin) and IGF-I, and this somatopause of aging suggests a connection between the neuroendocrine and immune systems. Several investigators have demonstrated that treatment with either growth hormone or IGF-I restores architecture of the involuted thymus gland by reversing the loss of immature cortical thymocytes and preventing the decline in thymulin synthesis that occurs in old or GH-deficient animals and humans. The proliferation, differentiation and functions of other components of the immune system, including T and B cells, macrophages and neutrophils, also demonstrate age-associated decrements that can be restored by IGF-I. Knowledge of the mechanism by which cytokines and hormones influence hematopoietic cells is critical to improving the health of aged individuals. Our laboratory has recently demonstrated that IGF-I prevents apoptosis in promyeloid cells, which subsequently permits these cells to differentiate into neutrophils. We also demonstrated that IL-4 acts much like IGF-I to promote survival of promyeloid cells and to activate the enzyme phosphatidylinositol 3'-kinase (PI 3-kinase). However, the receptors for IGF-I and IL-4 are completely different, with the intracellular beta chains of the IGF receptor possessing intrinsic tyrosine kinase activity and the alpha and gammac subunit of the heterodimeric IL-4 receptor utilizing the Janus kinase family of nonreceptor protein kinases to tyrosine phosphorylate downstream targets. Both receptors share many of the components of the PI 3-kinase signal transduction pathway, converging at the level of insulin receptor substrate-1 or insulin receptor subtrate-2 (formally known as 4PS, or IL-4 Phosphorylated Substrate). Our investigations with IGF-I and IL-4 suggest that PI 3-kinase inhibits apoptosis by maintaining high levels of

  1. Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association.

    Science.gov (United States)

    Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

    2015-06-29

    The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS.

  2. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

    Directory of Open Access Journals (Sweden)

    Luz Ibarra-Lara

    2016-12-01

    Full Text Available Renin-angiotensin system (RAS activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II/Angiotensin II type 1 receptor (AT1 and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia. Control and MetS rats were assigned to the following groups: (a sham; (b vehicle-treated myocardial infarction (MI (MI-V; and (c fenofibrate-treated myocardial infarction (MI-F. Treatment with fenofibrate significantly reduced triglycerides, non-high density lipoprotein cholesterol (non-HDL-C, insulin levels and insulin resistance index (HOMA-IR in MetS animals. MetS and MI increased Ang II concentration and AT1 expression, favored myocardial oxidative stress (high levels of malondialdehyde, overexpression of nicotinamide adenine dinucleotide phosphate (NADPH oxidase 4 (NOX4, decreased total antioxidant capacity and diminished expression of superoxide dismutase (SOD1, SOD2 and catalase and inhibited expression of the insulin signaling cascade: phosphatidylinositol 3-kinase (PI3K/protein kinase B (PkB, also known as Akt/Glut-4/endothelial nitric oxide synthase (eNOS. In conclusion, fenofibrate treatment favors an antioxidant environment as a consequence of a reduction of the Ang II/AT1/NOX4 signaling pathway, reestablishing the cardiac insulin signaling pathway. This might optimize cardiac metabolism and improve the vasodilator function during myocardial ischemia.

  3. Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome

    Science.gov (United States)

    Scott, David; Joham, Anju; Teede, Helena; Gibson-Helm, Melanie; Harrison, Cheryce; Cassar, Samantha; Hutchison, Samantha; Ebeling, Peter R.; Stepto, Nigel; de Courten, Barbora

    2016-01-01

    Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m2). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m2/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05). Higher IMAT was associated with lower 25OHD (B = −3.95; 95% CI −6.86, −1.05) and GIR (B = −21.3; 95% CI −37.16, −5.44) in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044), but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women. PMID:27916865

  4. Working Memory in Early-School-Age Children with Asperger's Syndrome

    Science.gov (United States)

    Cui, Jifang; Gao, Dingguo; Chen, Yinghe; Zou, Xiaobing; Wang, Ya

    2010-01-01

    Using a battery of working memory span tasks and n-back tasks, this study aimed to explore working memory functions in early-school-age children with Asperger's syndrome (AS). Twelve children with AS and 29 healthy children matched on age and IQ were recruited. Results showed: (a) children with AS performed better in digit and word recall tasks,…

  5. Sleep Patterns of School-Age Children with Asperger Syndrome or High-Functioning Autism

    Science.gov (United States)

    Allik, Hiie; Larsson, Jan-Olov; Smedje, Hans

    2006-01-01

    Sleep patterns of 32 school-age children with Asperger syndrome (AS) and high-functioning autism (HFA) were compared to those of 32 typically developing age- and gender-matched children, using parent survey and one week of diary and actigraphic monitoring. Parents of children with AS/HFA more commonly reported that their children had difficulty…

  6. Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome.

    Science.gov (United States)

    Jones, Emma L; Mok, Kin; Hanney, Marisa; Harold, Denise; Sims, Rebecca; Williams, Julie; Ballard, Clive

    2013-10-01

    It is known that individuals with Down syndrome develop Alzheimer's disease with an early age at onset, although associated genetic risk factors have not been widely studied. We tested whether genes that increase the risk of late-onset Alzheimer's disease influence the age at onset in Down syndrome using genome-wide association data for age at onset of dementia in a small sample of individuals (N = 67) with Down syndrome. We tested for association with loci previously associated with Alzheimer's disease risk and, despite the small size of the study, we detected associations with age at onset of Alzheimer's disease in Down syndrome with PICALM (β = 3.31, p = 0.011) and the APOE loci (β = 3.58, p = 0.014). As dementia in people with Down syndrome is relatively understudied, we make all of these data publicly available to encourage further analyses of the problem of Alzheimer's disease in Down syndrome.

  7. Insulin-like growth factor-I decreases serum lipoprotein (a) during long-term treatment of patients with Laron syndrome.

    Science.gov (United States)

    Laron, Z; Wang, X L; Klinger, B; Silbergeld, A; Wilcken, D E

    1996-10-01

    An increased circulating level of lipoprotein(a) [Lp(a)] is a well-recognized risk factor for coronary artery disease. While much remains to be understood about its regulation and physiological functions, we explored the effect of recombinant insulin-like growth factor-I (IGF-I) administration on circulating Lp(a) levels in 10 Laron syndrome (LS) patients (five children and five adults) with inherited IGF-I deficiency. There was no relationship between pretreatment or posttreatment Lp(a) levels and age and sex of the patients. With IGF-I treatment for 6 to 12 months, there was a significant reduction in Lp(a) (65.7% +/- 15.5%, P < .0001) from the pretreatment level of 76 +/- 45 mg/L to the posttreatment level of 29 +/- 26 mg/L. This decrease was dosage-dependent on the IGF-I administered (r = .685, F = 0.708, P = .029) and correlated more strongly with the dosage ratio of the end to the beginning of treatment (r = .78, F = 12.23, P = .008). The higher the IGF-I dose and the higher the dose ratio, the greater the Lp(a) decrease and the lower the Lp(a) at the end of treatment. In conclusion, we observed a dose-dependent relationship between IGF-I administration and Lp(a) reduction in patients with LS. Further studies are needed to elucidate the mechanism of the effect, but our findings suggest a possible metabolic link between these two and shed more light on the regulation of apolipoprotein(a) [apo(a)] expression. It could also open an avenue for additional therapeutic usage of IGF-I.

  8. Alternative splicing of exon 17 and a missense mutation in exon 20 of the insulin receptor gene in two brothers with a novel syndrome of insulin resistance (congenital fiber-type disproportion myopathy).

    Science.gov (United States)

    Vorwerk, P; Christoffersen, C T; Müller, J; Vestergaard, H; Pedersen, O; De Meyts, P

    1999-01-01

    The insulin receptor (IR) in two brothers with a rare syndrome of congenital muscle fiber type disproportion myopathy (CFTDM) associated with diabetes and severe insulin resistance was studied. By direct sequencing of Epstein-Barr virus-transformed lymphocytes both patients were found to be compound heterozygotes for mutations in the IR gene. The maternal allele was alternatively spliced in exon 17 due to a point mutation in the -1 donor splice site of the exon. The abnormal skipping of exon 17 shifts the amino acid reading frame and leads to a truncated IR, missing the entire tyrosine kinase domain. In the correct spliced variant, the point mutation is silent and results in a normally translated IR. The paternal allele carries a missense mutation in the tyrosine kinase domain. All three cDNA variants were present in the lymphocytes of the patients. Purified IR from 293 cells overexpressing either of the two mutated receptors lacked basal or stimulated IR beta-subunit autophosphorylation. A third brother who inherited both normal alleles has an normal muscle phenotype and insulin sensitivity, suggesting a direct linkage of these IR mutations with the CFTDM phenotype.

  9. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  10. Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Rattan, Suresh;

    2000-01-01

    Age-related bone loss is thought to be due to impaired osteoblast functions. Insulin-like growth factors (IGFs) have been shown to be important stimulators of bone formation and osteoblast activities in vitro and in vivo. We tested the hypothesis that in vitro osteoblast senescence is associated ...

  11. Longitudinal changes in insulin sensitivity and body composition of small-for-gestational-age adolescents after cessation of growth hormone treatment

    NARCIS (Netherlands)

    R.H. Willemsen (Ruben); A.C.S. Hokken-Koelega (Anita)

    2008-01-01

    textabstractContext: GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, β-cell function, and body composition change over time after stoppin

  12. Repeated Insulin-like Growth Factor 1 (IGF1 treatment in a patient with Rett Syndrome: a single case study

    Directory of Open Access Journals (Sweden)

    Giorgio ePini

    2014-06-01

    Full Text Available Rett syndrome (RTT is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor and speech impairment, cardio-respiratory distress, microcephaly and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2, which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, Insulin-like growth Factor 1 (IGF1 and its active peptide (1-3IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle we monitored the clinical and blood parameters, autonomic function and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the preclinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  13. No association of the insulin gene VNTR polymorphism with polycystic ovary syndrome in a Han Chinese population

    Directory of Open Access Journals (Sweden)

    Gao Guihua

    2009-12-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a common endocrine disorder associated with an increased risk of type II diabetes mellitus. The results of previous research about the association of the VNTR polymorphism in 5-prime flanking region of the insulin (INS gene with PCOS have been inconsistent. The present study was to investigate the association of the INS-VNTR polymorphism with PCOS in a Han Chinese population. Methods The -23/HphI polymorphism as a surrogate marker of the INS-VNTR length polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP in 216 PCOS patients and 192 non-PCOS women as a control group. Allelic and genotypic frequencies were compared between patients and controls, and these results were analyzed in respect to clinical test data. Results No significant differences were observed between the cases and controls groups either in allele (P = 0.996 or genotype (P = 0.802 frequencies of INS-VNTR polymorphism; Regarding anthropometric data and hormone levels, there were no significant differences between INS-VNTR genotypes in the PCOS group, as well as in the non-PCOS group. Conclusion The present study demonstrated for the first time that the INS-VNTR polymorphism is not a key risk factor for sporadic PCOS in the Han Chinese women. Further studies are needed to give a global view of this polymorphism in pathogenesis of PCOS in a large-scale sample, family-based association design or well-defined subgroups of PCOS.

  14. Repeated insulin-like growth factor 1 treatment in a patient with rett syndrome: a single case study.

    Science.gov (United States)

    Pini, Giorgio; Scusa, M Flora; Benincasa, Alberto; Bottiglioni, Ilaria; Congiu, Laura; Vadhatpour, Cyrus; Romanelli, Anna Maria; Gemo, Ilaria; Puccetti, Chetti; McNamara, Rachel; O'Leary, Seán; Corvin, Aiden; Gill, Michael; Tropea, Daniela

    2014-01-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disorder that has no cure. Patients show regression of acquired skills, motor, and speech impairment, cardio-respiratory distress, microcephaly, and stereotyped hand movements. The majority of RTT patients display mutations in the gene that codes for the Methyl-CpG binding protein 2 (MeCP2), which is involved in the development of the central nervous system, especially synaptic and circuit maturation. Thus, agents that promote brain development and synaptic function are good candidates for ameliorating the symptoms of RTT. In particular, insulin-like growth factor 1 (IGF1) and its active peptide (1-3) IGF1 cross the Blood Brain Barrier, and therefore are ideal treatments for RTT Indeed, both (1-3) IGF1 and IGF1 treatment significantly ameliorates RTT symptoms in a mouse model of the disease In a previous study, we established that IGF1 is safe and well tolerated on Rett patients. In this open label clinical case study, we assess the safety and tolerability of IGF1 administration in two cycles of the treatment. Before and after each cycle, we monitored the clinical and blood parameters, autonomic function, and social and cognitive abilities, and we found that IGF1 was well tolerated each time and did not induce any side effect, nor it interfered with the other treatments that the patient was undergoing. We noticed a moderate improvement in the cognitive, social, and autonomic abilities of the patient after each cycle but the benefits were not retained between the two cycles, consistent with the pre-clinical observation that treatments for RTT should be administered through life. We find that repeated IGF1 treatment is safe and well tolerated in Rett patients but observed effects are not retained between cycles. These results have applications to other pathologies considering that IGF1 has been shown to be effective in other disorders of the autism spectrum.

  15. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne;

    2008-01-01

    OBJECTIVE: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo ...... improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance in PCOS. Udgivelsesdato: 2008-Feb...... for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. RESULTS...

  16. 胰岛素抵抗综合征的护理进展%Development in Nursing of Insulin Resistance Syndrome

    Institute of Scientific and Technical Information of China (English)

    余峰彬

    2004-01-01

    @@ 胰岛素抵抗综合征(insulin resistance syndrome,IRS)是指由于胰岛素抵抗(insulin resistance,IR)及其派生的糖、脂肪代谢紊乱所导致的一群疾病或病症.IR是指胰岛素的外周靶组织(主要为骨骼肌、肝脏和脂肪组织)对内源性或外源性胰岛素的敏感性和反应性降低,导致生理剂量的胰岛素产生低于正常的生理效应.

  17. Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues.

    Science.gov (United States)

    Kochkina, Ekaterina G; Plesneva, Svetlana A; Vasilev, Dmitrii S; Zhuravin, Igor A; Turner, Anthony J; Nalivaeva, Natalia N

    2015-08-01

    Due to an increasing life expectancy in developing countries, cases of type 2 diabetes and Alzheimer's disease (AD) in the elderly are growing exponentially. Despite a causative link between diabetes and AD, general molecular mechanisms underlying pathogenesis of these disorders are still far from being understood. One of the factors leading to cell death and cognitive impairment characteristic of AD is accumulation in the brain of toxic aggregates of amyloid-β peptide (Aβ). In the normally functioning brain Aβ catabolism is regulated by a cohort of proteolytic enzymes including insulin-degrading enzyme (IDE) and their deficit with ageing can result in Aβ accumulation and increased risk of AD. The aim of this study was a comparative analysis of IDE expression in the brain structures involved in AD, as well as in peripheral organs (the liver and kidney) of rats, during natural ageing and after experimentally-induced diabetes. It was found that ageing is accompanied by a significant decrease of IDE mRNA and protein content in the liver (by 32 and 81%) and brain structures (in the cortex by 58 and 47% and in the striatum by 53 and 68%, respectively). In diabetic animals, IDE protein level was increased in the liver (by 36%) and in the striatum (by 42%) while in the brain cortex and hippocampus it was 20-30% lower than in control animals. No significant IDE protein changes were observed in the kidney of diabetic rats. These data testify that ageing and diabetes are accompanied by a deficit of IDE in the brain structures where accumulation of Aβ was reported in AD patients, which might be one of the factors predisposing to development of the sporadic form of AD in the elderly, and especially in diabetics.

  18. Plasma adiponectin levels are increased despite insulin resistance in corticotropin-releasing hormone transgenic mice, an animal model of Cushing syndrome.

    Science.gov (United States)

    Shinahara, Masayuki; Nishiyama, Mitsuru; Iwasaki, Yasumasa; Nakayama, Shuichi; Noguchi, Toru; Kambayashi, Machiko; Okada, Yasushi; Tsuda, Masayuki; Stenzel-Poore, Mary P; Hashimoto, Kozo; Terada, Yoshio

    2009-01-01

    Adiponectin (AdN), an adipokine derived from the adipose tissue, has an insulin-sensitizing effect, and plasma AdN is shown to be decreased in obesity and/or insulin resistant state. To clarify whether changes in AdN are also responsible for the development of glucocorticoid-induced insulin resistance, we examined AdN concentration in plasma and AdN expression in the adipose tissue, using corticotropin-releasing hormone (CRH) transgenic mouse (CRH-Tg), an animal model of Cushing syndrome. We found, unexpectedly, that plasma AdN levels in CRHTg were significantly higher than those in wild-type littermates (wild-type: 19.7+/-2.5, CRH-Tg: 32.4+/-3.1 microg/mL, pAdN mRNA and protein levels were significantly decreased in the adipose tissue of CRH-Tg. Bilateral adrenalectomy in CRH-Tg eliminated both their Cushing's phenotype and their increase in plasma AdN levels (wild-type/sham: 9.4+/-0.5, CRH-Tg/sham: 15.7+/-2.0, CRH-Tg/ADX: 8.5+/-0.4 microg/mL). These results strongly suggest that AdN is not a major factor responsible for the development of insulin resistance in Cushing syndrome. Our data also suggest that glucocorticoid increases plasma AdN levels but decreases AdN expression in adipocytes, the latter being explained possibly by the decrease in AdN metabolism in the Cushing state.

  19. Polycystic ovary syndrome: clinical implication in perimenopause

    OpenAIRE

    Monika Lenart-Lipińska; Beata Matyjaszek-Matuszek; Ewa Woźniakowska; Janusz Solski; Tarach, Jerzy S.; Tomasz Paszkowski

    2014-01-01

    Polycystic ovary syndrome (PCOS), a hyperandrogenic disorder, is the commonest endocrinopathy in premenopausal women. This syndrome is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbances, particularly insulin resistance and obesity. There is a great body of evidence that patients with PCOS present multiple cardiovascular risk factors and cluster components of metabolic syndrome from early ages. The presence of comorbidities such as abdomi...

  20. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.

    1991-01-01

    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  1. Expression of human apolipoprotein E4 reduces insulin-receptor substrate 1 expression and Akt phosphorylation in the ageing liver

    Directory of Open Access Journals (Sweden)

    Qi-Rui Ong

    2014-01-01

    Full Text Available The diabetic drug rosiglitazone was reported to improve glucose tolerance in insulin-resistant ApoE3 but not ApoE4 knock-in mice. We therefore examined whether apolipoprotein E (ApoE has genotype-specific effects on liver insulin function. At 12 weeks, no difference in liver insulin signaling was detected between fasting ApoE3 and ApoE4 mice. At 72 weeks however, ApoE4 mice had lower IRS-1 and PI3K expression, and reduced Akt phosphorylation. This decline was associated with lower insulin and higher glucose in ApoE4 mouse liver. Liver cholesterol was not affected. These results show that ApoE4 expression reduces liver insulin signaling and insulin levels, leading to higher glucose content.

  2. Models for estimating the metabolic syndrome biological age as the new index for evaluation and management of metabolic syndrome

    Science.gov (United States)

    Kang, Young Gon; Suh, Eunkyung; Chun, Hyejin; Kim, Sun-Hyun; Kim, Deog Ki; Bae, Chul-Young

    2017-01-01

    Purpose This study aims to propose a metabolic syndrome (MS) biological age model, through which overall evaluation and management of the health status and aging state in MS can be done easily. Through this model, we hope to provide a novel evaluation and management health index that can be utilized in various health care fields. Patient and methods MS parameters from American Heart Association/National Heart, Lung, and Blood Institute guidelines in 2005 were used as biomarkers for the estimation of MS biological age. MS biological age model development was done by analyzing data of 263,828 participants and clinical application of the developed MS biological age was assessed by analyzing the data of 188,886 subjects. Results The principal component accounted for 36.1% in male and 38.9% in female of the total variance in the battery of five variables. The correlation coefficient between corrected biological age and chronological age in males and females were 0.711 and 0.737, respectively. Significant difference for mean MS biological age and chronological age between the three groups, normal, at risk and MS, was seen (P<0.001). Conclusion For the comprehensive approach in MS management, MS biological age is expected to be additionally utilized as a novel evaluation and management index along with the traditional MS diagnosis. PMID:28203066

  3. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala varian...... of body composition (BMI and waist circumference). In conclusion, homozygosity of the codon 12 variant of PPAR-gamma 2 confers a reduced risk of the IRS among Danish Caucasian subjects.......The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala variant...

  4. Cochlear hearing loss in patients with Laron syndrome.

    Science.gov (United States)

    Attias, Joseph; Zarchi, Omer; Nageris, Ben I; Laron, Zvi

    2012-02-01

    The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.

  5. 超声诊断脂肪肝与胰岛素抵抗及代谢综合征的相关性%Association between Insulin Resistance,Metabolic Syndrome and Ultrasound diagnosis of Fatty Liver

    Institute of Scientific and Technical Information of China (English)

    杨艳红

    2014-01-01

    Objective To investigate tje association between insulin resistance,metabolic syndrome( MS)and Ultrasound diagnosis of fatty liver. Method Fifty subjects witj NAFLD and 56 controls were enrolled for tje study. All subjects underwent ultrasound examinations, meanwjile waist circumference,blood pressure,fasting glucose,fasting insulin,serum lipids and jomeostasis model assessment of insulin re-sistance( HOMA-IR)values as an index used to quantify insulin resistance were measured and analyzed. Logistic regression was analyzed to predict independent risk factors of NAFLD. Results Tje prevalence of MS in NAFLD group was obviously jigjer tjan in controls group (48. 0% VS 5. 4%,P<0. 001),and HOMA-IR values in NAFLD group was jigjer tjan tjat of controls group(2. 65 ± 1. 35 VS 1. 45 ± 1. 02,P<0. 001). In a logistic regression analysis,age,waist circumference and HOMA-IR were independently associated witj tje pres-ence of NAFLD. Conclusion NAFLD was closely associated witj MS and insulin resistance was a very strong predictor of NAFLD.%目的:探讨超声诊断脂肪肝( NAFLD)与胰岛素抵抗及代谢综合征( MS)的相关性。方法:50例NAFLD患者及56例健康对照者分别进行超声检查,同时测定腰围、血压、空腹血糖、空腹胰岛素、血脂等,计算胰岛素抵抗指数( HOMA-IR),并作相关统计学分析。结果:NAFLD组的MS发病率明显高于对照组(48.0% VS 5.4%,P<0.001),且NAFLD组的HOMA-IR明显高于对照组(2.65±1.35 VS 1.45±1.02,P<0.001)。Logistic回归分析表明年龄,腰围,HOMA-IR为NAFLD的独立危险因素。结论:NAFLD与MS密切相关,胰岛素抵抗是NAFLD的独立危险因素。

  6. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  7. Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome

    DEFF Research Database (Denmark)

    Wikström, Anne M; Bay, Katrine; Hero, Matti;

    2006-01-01

    Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development.......Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development....

  8. miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1)

    Science.gov (United States)

    Xiang, Yungai; Song, Yuxia; Li, Yan; Zhao, Dongmei; Ma, Liying; Tan, Li

    2016-01-01

    Background Polycystic ovarian syndrome (PCOS) is a common metabolic disorder in premenopausal woman, characterized by hyperandrogenism, oligoanovulation, and insulin resistance. microRNAs play pivotal roles in regulating key factors of PCOS. However, relevant research remains limited. This study aimed to reveal the role and potential mechanism of miR-483 in PCOS. Material/Methods PCOS patients (n=20) were recruited for detecting miR-483 expression in lesion and normal ovary cortex. Human granulosa-like tumor cell line KGN was used to alter miR-483 expression by cell transfection. Cell viability and proliferation were analyzed by MTT assay and colony formation assay, and cell cycle was detected by flow cytometry. Interaction between miR-483 and IGF1 was verified by luciferase reporter assay. KGN cells were further treated by insulin to investigate the relationship between miR-483 and insulin. Results miR-483 was significantly down-regulated in lesion ovary cortex from PCOS patients (P<0.001). In KGN cells, overexpression of miR-483 inhibited cell viability and proliferation, and induced cell cycle arrest. miR-483 also inhibited CCNB1, CCND1, and CDK2. miR-483 sponge induced the opposite effects. miR-483 directly targeted IGF1 3′UTR, and IGF1 promoted KGN cell proliferation and reversed miR-483-inhibited cell viability. Insulin treatment in KGN cells inhibited miR-483, and promoted IGF1 and cell proliferation. Conclusions These results suggest that miR-483 is a PCOS suppressor inhibiting cell proliferation, possibly via targeting IGF1, and that it is involved in insulin-induced cell proliferation. miR-483 is a potential alternative for diagnosing and treating PCOS. PMID:27662007

  9. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala varian...... of body composition (BMI and waist circumference). In conclusion, homozygosity of the codon 12 variant of PPAR-gamma 2 confers a reduced risk of the IRS among Danish Caucasian subjects....

  10. 47,XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management.

    Science.gov (United States)

    Aksglaede, Lise; Link, Katarina; Giwercman, Aleksander; Jørgensen, Niels; Skakkebaek, Niels E; Juul, Anders

    2013-02-15

    47,XXY (Klinefelter syndrome) is the most frequent sex chromosomal disorder and affects approximately one in 660 newborn boys. The syndrome is characterized by varying degrees of cognitive, social, behavioral, and learning difficulties and in adulthood additionally primary testicular failure with small testes, hypergonadotropic hypogonadism, tall stature, and eunuchoid body proportions. The phenotype is variable ranging from "near-normal" to a significantly affected individual. In addition, newborns with Klinefelter syndrome generally present with a normal male phenotype and the only consistent clinical finding in KS is small testes, that are most often not identified until after puberty. Decreased awareness of this syndrome among health professionals and a general perception that all patients with 47,XXY exhibit the classic textbook phenotype results in a highly under-diagnosed condition with up to 75% of the patients left undetected. Typically, diagnosis is delayed with the majority of patients identified during fertility workup in adulthood, and only 10% of patients diagnosed prior to puberty. Early detection of this syndrome is recommended in order to offer treatment and intervention at the appropriate ages and stages of development for the purpose of preventing osteopenia/osteoporosis, metabolic syndrome, and other medical conditions related to hypogonadism and to the XXY as well as minimizing potential learning and psychosocial problems. The aim of this review is to present the clinical aspects of XXY and the age-specific recommendations for medical management. © 2013 Wiley Periodicals, Inc.

  11. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, stru...

  12. Insulin resistance, the metabolic syndrome, and risk of incident cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine W; Rasmussen, Susanne

    2007-01-01

    , and NCEP-HOMA-IR as belonging to the highest 16% of the HOMA-IR distribution. RESULTS: Over a median follow-up of 9.4 years, the incidence of CV end points (CV death, nonfatal ischemic heart disease, and nonfatal stroke) amounted to 233 cases. In proportional hazard models, adjusting for age, gender......, smoking, and low-density lipoprotein cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to 2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The corresponding figures for NCEP......-HOMA-IR and NCEP-MetSyn included in the same model were 1.49 (95% CI 1.07 to 2.07) and 1.56 (95% CI 1.12 to 2.17). CONCLUSIONS: In this Danish study, both HOMA-IR and NCEP-MetSyn were independent predictors of incident CVD....

  13. The Use of Mouse Models for Understanding the Biology of Down Syndrome and Aging

    Directory of Open Access Journals (Sweden)

    Guido N. Vacano

    2012-01-01

    Full Text Available Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress in their production and analysis has been remarkable. Here, we describe various mouse models that have been used to study Down syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to human chromosome 21, mice in which individual genes have been introduced, or mice in which genes have been silenced by targeted mutagenesis. We selected a limited number of genes for which considerable evidence links them to aspects of Down syndrome, and about which much is known regarding their function. We focused on genes important for brain and cognitive function, and for the altered cancer spectrum seen in individuals with Down syndrome. We conclude with observations on the usefulness of mouse models and speculation on future directions.

  14. The use of mouse models for understanding the biology of down syndrome and aging.

    Science.gov (United States)

    Vacano, Guido N; Duval, Nathan; Patterson, David

    2012-01-01

    Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress in their production and analysis has been remarkable. Here, we describe various mouse models that have been used to study Down syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to human chromosome 21, mice in which individual genes have been introduced, or mice in which genes have been silenced by targeted mutagenesis. We selected a limited number of genes for which considerable evidence links them to aspects of Down syndrome, and about which much is known regarding their function. We focused on genes important for brain and cognitive function, and for the altered cancer spectrum seen in individuals with Down syndrome. We conclude with observations on the usefulness of mouse models and speculation on future directions.

  15. Accelerated fat cell aging links oxidative stress and insulin resistance in adipocytes

    Indian Academy of Sciences (India)

    Finny Monickaraj; Sankaramoorthy Aravind; Pichamoorthy Nandhini; Paramasivam Prabu; Chandrakumar Sathishkumar; Viswanathan Mohan; Muthuswamy Balasubramanyam

    2013-03-01

    Telomere shortening is emerging as a biological indicator of accelerated aging and aging-related diseases including type 2 diabetes. While telomere length measurements were largely done in white blood cells, there is lack of studies on telomere length in relation to oxidative stress in target tissues affected in diabetes. Therefore, the aim of this study is to induct oxidative stress in adipocytes and to test whether these adipocytes exhibit shortened telomeres, senescence and functional impairment. 3T3-L1 adipocytes were subjected to oxidative stress and senescence induction by a variety of means for 2 weeks (exogenous application of H2O2, glucose oxidase, asymmetric dimethylarginine (ADMA) and glucose oscillations). Cells were probed for reactive oxygen species generation (ROS), DNA damage, mRNA and protein expression of senescent and pro-inflammatory markers, telomere length and glucose uptake. Compared to untreated cells, both ROS generation and DNA damage were significantly higher in cells subjected to oxidative stress and senescence. Adipocytes subjected to oxidative stress also showed shortened telomeres and increased mRNA and protein expression of p53, p21, TNF and IL-6. Senescent cells were also characterized by decreased levels of adiponectin and impaired glucose uptake. Briefly, adipocytes under oxidative stress exhibited increased ROS generation, DNA damage, shortened telomeres and switched to senescent/pro-inflammatory phenotype with impaired glucose uptake.

  16. The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect.

    Science.gov (United States)

    Yoon, Song-Ro; Qin, Jian; Glaser, Rivka L; Jabs, Ethylin Wang; Wexler, Nancy S; Sokol, Rebecca; Arnheim, Norman; Calabrese, Peter

    2009-07-01

    Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

  17. The ups and downs of mutation frequencies during aging can account for the Apert syndrome paternal age effect.

    Directory of Open Access Journals (Sweden)

    Song-Ro Yoon

    2009-07-01

    Full Text Available Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2. The incidence of this disease increases with the age of the father (paternal age effect, and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

  18. Longitudinal increase in gamma-glutamyltransferase within the reference interval predicts metabolic syndrome in middle-aged Korean men.

    Science.gov (United States)

    Ryu, Seungho; Chang, Yoosoo; Woo, Hee-Yeon; Yoo, Sang-Ho; Choi, Nam-Kyong; Lee, Won-Young; Kim, Inah; Song, Jaechul

    2010-05-01

    In the absence of existing research, we examined the association between longitudinal changes in serum gamma-glutamyltransferase (GGT) levels and the risk for metabolic syndrome (MetS). A MetS-free cohort of 9148 healthy male workers, who had participated in a health checkup program in 2002, was followed until September 2007. Metabolic syndrome was defined according to the modified National Cholesterol Education Program, using body mass index instead of waist circumference. Standard Cox proportional hazards and time-dependent Cox models were performed. During 37 663.4 person-years of follow-up, 1056 men developed MetS. The risk of incident MetS increased across the baseline GGT quartiles, even after further updating GGT values during the follow-up. A longitudinal increase in GGT as a time-dependent variable as well as a non-time-dependent variable was significantly related to MetS after adjusting for age plus the elapsed time from visit 1 to visit 2, baseline MetS traits, uric acid, regular exercise, alcohol consumption, and smoking. Even within the GGT reference interval (interval, 1.26-2.07). Furthermore, these associations were consistently observed within the subgroups-those with body mass index less than 23 kg/m(2), C-reactive protein less than 3.0 mg/L, homeostasis model assessment of insulin resistance less than 2.04, alcohol intake not exceeding 20 g/d, alanine aminotransferase less than 35 U/L, an absence of ultrasonographically detected fatty liver, and an absence of any MetS traits. A longitudinal increase in the GGT level, even within the GGT reference interval, may be an independent predictor for MetS, regardless of the baseline GGT.

  19. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Sancheti, Harsh; Akopian, Garnik; Yin, Fei; Brinton, Roberta D; Walsh, John P; Cadenas, Enrique

    2013-01-01

    Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits) and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD) that shows progression of pathology as a function of age; two age groups: 6 months (young) and 12 months (old) were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O) and long term potentiation (LTP) (measured by electrophysiology). Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  20. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  1. Insulin autoimmune syndrome in 1 case and review of the literature%胰岛素自身免疫综合征1例

    Institute of Scientific and Technical Information of China (English)

    王艳

    2014-01-01

    目的:胰岛素自身免疫综合征(IAS)为少见疾病。通过报道1例IAS及文献复习,讨论IAS的诊治及预后。临床上对伴有自身免疫疾病、服用含巯基药物的高胰岛素性、低血糖症患者,应检测胰岛素自身抗体,以避免误诊和不必要的手术。%Insulin autoimmune syndrome(IAS) is a rare disease.Through the report of 1 case of IAS and review of the literature, we discuss the diagnosis and prognosis of IAS.Clinically.For some patients,such as associated with autoimmune diseases,taking high insulin of sulfydryl containing drugs,and hypoglycemia patients,insulin autoantibodies should be detected in order to avoid misdiagnosis and unnecessary operation.

  2. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-06-13

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  3. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    Maria Jose Sáez-Lara

    2016-06-01

    Full Text Available The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS, type 2 diabetes (T2D and non-alcoholic fatty liver disease (NAFLD in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

  4. Efficacy, safety and cost-effectiveness of insulin sensitizers as add-on therapy in metabolic syndrome in patients with secondary sulfonylurea failure: A comparative study

    Directory of Open Access Journals (Sweden)

    Rajiv Mahajan

    2010-01-01

    Full Text Available Objectives: Prevalence of metabolic syndrome (MS is ~25% and it is currently becoming prevalent in children also. India is estimated to have the maximum number of patients of MS in the world. As insulin resistance is an integral part of MS and the rate of secondary sulfonylurea failure (SSUF is also high, the present study was planned to evaluate the effects of insulin sensitizers as add-on therapy in MS with SSUF. Materials and Methods: An open-label, prospective, randomized study was conducted on 200 patients of MS with SSUF, included according to ATP III criteria, after dividing them into two groups. Group I patients were given pioglitazone 30 mg/day while group II patients were given metformin 1,000 mg/day as add-on therapy to the sulfonylurea already prescribed. Results: Fall in fasting blood glucose, glycosylated hemoglobin and serum triglycerides was higher with metformin, but rise in high-density lipoprotein-cholesterol was higher with pioglitazone. Only metformin caused a significant reduction in body mass index. Significant reduction in waist circumference, systolic blood pressure and diastolic blood pressure was not seen with any therapy. Incremental cost-effective ratio was almost six-times higher with pioglitazone. Conclusion: Among insulin sensitizers, metformin has more favorable, persistent and multifacet effects in MS with SSUF. Studies of longer duration are required for calculating reduction in the mortality and morbidity.

  5. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials

    Science.gov (United States)

    Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

    2016-01-01

    The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders. PMID:27304953

  6. Onset of Dyspraxia in Aging Persons with Down Syndrome: Longitudinal Studies.

    Science.gov (United States)

    Dalton, Arthur J.; Fedor, Bettye L.

    1998-01-01

    Because dyspraxia (partial loss of the ability to perform purposeful motor acts) is an early symptom of Alzheimer disease, a 62-item dyspraxia scale adapted for adults with Down syndrome (DS) was developed. Use of the measure over 3.5 years with 72 DS individuals (age 40 or older) found statistically significant deterioration that suggested…

  7. Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome

    NARCIS (Netherlands)

    Hirschtritt, Matthew E; Lee, Paul C; Pauls, David L; Dion, Yves; Grados, Marco A; Illmann, Cornelia; King, Robert A; Sandor, Paul; McMahon, William M; Lyon, Gholson J; Cath, Danielle C; Kurlan, Roger; Robertson, Mary M; Osiecki, Lisa; Scharf, Jeremiah M; Mathews, Carol A

    2015-01-01

    IMPORTANCE: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-asso

  8. Ageing and Dementia in a Longitudinal Study of a Cohort with Down Syndrome

    Science.gov (United States)

    Carr, Janet; Collins, Suzanne

    2014-01-01

    Background: A population sample of people with Down syndrome has been studied from infancy and has now been followed up again at age 47 years. Methods: Intelligence and language skills were tested and daily living skills assessed. Memory/cognitive deterioration was examined using two test instruments. Results: Scores on verbal tests of…

  9. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link?

    Science.gov (United States)

    Miyamoto, Michael I; Djabali, Karima; Gordon, Leslie B

    2014-06-01

    Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging.

  10. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome

    Science.gov (United States)

    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases. PMID:23257959

  11. Aberrant DNA methylation profiles in the premature aging disorders Hutchinson-Gilford Progeria and Werner syndrome.

    Science.gov (United States)

    Heyn, Holger; Moran, Sebastian; Esteller, Manel

    2013-01-01

    DNA methylation gradiently changes with age and is likely to be involved in aging-related processes with subsequent phenotype changes and increased susceptibility to certain diseases. The Hutchinson-Gilford Progeria (HGP) and Werner Syndrome (WS) are two premature aging diseases showing features of common natural aging early in life. Mutations in the LMNA and WRN genes were associated to disease onset; however, for a subset of patients the underlying causative mechanisms remain elusive. We aimed to evaluate the role of epigenetic alteration on premature aging diseases by performing comprehensive DNA methylation profiling of HGP and WS patients. We observed profound changes in the DNA methylation landscapes of WRN and LMNA mutant patients, which were narrowed down to a set of aging related genes and processes. Although of low overall variance, non-mutant patients revealed differential DNA methylation at distinct loci. Hence, we propose DNA methylation to have an impact on premature aging diseases.

  12. [THE OPTIMIZATION OF NUTRITION FUNCTION UNDER SYNDROME OF RESISTANCE TO INSULIN, DISORDER OF FATTY ACIDS' METABOLISM AND ABSORPTION OF GLUCOSE BY CELLS (A LECTURE)].

    Science.gov (United States)

    Titov, V N

    2016-01-01

    The phylogenetic processes continue to proceed in Homo Sapiens. At the very early stages ofphylogenesis, the ancient Archaea that formed mitochondria under symbiotic interaction with later bacterial cells conjointly formed yet another system. In this system, there are no cells' absorption of glucose if it is possible to absorb fatty acids from intercellular medium in the form of unesterfied fatty acids or ketonic bodies--metabolites of fatty acids. This is caused by objectively existed conditions and subsequent availability of substrates at the stages ofphylogenesis: acetate, ketonic bodies, fatty acids and only later glucose. The phylogenetically late insulin used after billions years the same dependencies at formation of regulation ofmetabolism offatty acids and cells' absorption of glucose. In order that syndrome ofresistance ceased to exist as afoundation of metabolic pandemic Homo Sapiens has to understand the following. After successful function ofArchaea+bacterial cells and considered by biology action of insulin for the third time in phylogenesis and using biological function of intelligence the content ofphylogenetically earlier palmitic saturated fatty acid infood can't to exceed possibilities of phylogenetically late lipoproteins to transfer it in intercellular medium and blood and cells to absorb it. It is supposed that at early stages of phylogenesis biological function of intelligence is primarily formed to bring into line "unconformities" of regulation of metabolism against the background of seeming relative biological "perfection". These unconformities were subsequently and separately formed at the level of cells in paracrin regulated cenosises of cells and organs and at the level of organism. The prevention of resistance to insulin basically requires biological function of intelligence, principle of self-restraint, bringing into line multiple desires of Homo Sapiens with much less extensive biological possibilities. The "unconformities" of

  13. The effect of a fibre supplement compared to a healthy diet on body composition, lipids, glucose, insulin and other metabolic syndrome risk factors in overweight and obese individuals.

    Science.gov (United States)

    Pal, Sebely; Khossousi, Alireza; Binns, Colin; Dhaliwal, Satvinder; Ellis, Vanessa

    2011-01-01

    Optimum levels and types of dietary fibre that provide the greatest beneficial effects on metabolic syndrome risk factors in overweight and obese individuals have yet to be determined in clinical trials. The present parallel design study compared the effects of fibre intake from a healthy diet v. a fibre supplement (psyllium) or a healthy diet plus fibre supplement on fasting lipids, glucose, insulin and body composition. Overweight/obese adults were randomised to either control (with placebo), fibre supplement (FIB), healthy eating plus placebo (HLT) or healthy eating plus fibre supplement (HLT-FIB). There was a significant increase in fibre intake in HLT-FIB, HLT and FIB groups up to 59, 31 and 55 g, respectively, at 12 weeks when compared to control (20 g). Weight, BMI and % total body fat were significantly reduced in FIB and HLT-FIB groups, with weight and BMI significantly reduced in the HLT group compared with control at 12 weeks. HLT-FIB and HLT groups had significant reductions in TAG and insulin compared with control at 6 and 12 weeks, and in insulin compared with the FIB group at 12 weeks. The HLT-FIB, HLT and FIB groups all had significant reductions in total cholesterol and LDL-cholesterol compared with control after 6 and 12 weeks. The present study demonstrated that simply adding psyllium fibre supplementation to a normal diet was sufficient to obtain beneficial effects in risk factors. However, a high-fibre diet consisting of a psyllium supplement plus fibre from a healthy diet provided the greatest improvements in metabolic syndrome risk factors.

  14. miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance.

    Science.gov (United States)

    Chen, Yen-Hao; Heneidi, Saleh; Lee, Jung-Min; Layman, Lawrence C; Stepp, David W; Gamboa, Gloria Mabel; Chen, Bo-Shiun; Chazenbalk, Gregorio; Azziz, Ricardo

    2013-07-01

    Approximately 70% of women with polycystic ovary syndrome (PCOS) have intrinsic insulin resistance (IR) above and beyond that associated with body mass, including dysfunctional glucose metabolism in adipose tissue (AT). In AT, analysis of the IRS/PI3-K/AKT pathway signaling components identified only GLUT4 expression to be significantly lower in PCOS patients and in control subjects with IR. We examined the role of miRNAs, particularly in the regulation of GLUT4, the insulin-sensitive glucose transporter, in the AT of PCOS and matched control subjects. PCOS AT was determined to have a differentially expressed miRNA profile, including upregulated miR-93, -133, and -223. GLUT4 is a highly predicted target for miR-93, while miR-133 and miR-223 have been demonstrated to regulate GLUT4 expression in cardiomyocytes. Expression of miR-93 revealed a strong correlation between the homeostasis model assessment of IR in vivo values and GLUT4 and miR-93 but not miR-133 and -223 expression in human AT. Overexpression of miR-93 resulted in downregulation of GLUT4 gene expression in adipocytes through direct targeting of the GLUT4 3'UTR, while inhibition of miR-93 activity led to increased GLUT4 expression. These results point to a novel mechanism for regulating insulin-stimulated glucose uptake via miR-93 and demonstrate upregulated miR-93 expression in all PCOS, and in non-PCOS women with IR, possibly accounting for the IR of the syndrome. In contrast, miR-133 and miR-223 may have a different, although yet to be defined, role in the IR of PCOS.

  15. Parental age and unbalanced Robertsonian translocations associated with Down syndrome and Patau syndrome: comparison with maternal and paternal age effects for 47, +21 and 47, +13.

    Science.gov (United States)

    Hook, E B

    1984-10-01

    Data are analysed on livebirths with trisomic syndromes associated with unbalanced Robertsonian translocations born from 1968 to 1981 and reported to the New York State Chromosome Registry. The maternal ages of reported cases were compared with those of the livebirths in the general population who were born in the same year. The number of translocations studied, the mean case-control differences in years in maternal age (and the standard errors of the mean) were respectively, as follows: D/21 mutants, n = 36, -0.1 (+/- 0.9); G/21 mutants, n = 46, +1.5 (+/-0.8); D/13 mutants, n = 16, +0.6 (+/-1.5); D/21 inherited, n = 12, -1.0 (+/-1.4); G/21 inherited, n = 3, -0.3 (+/-4.4); and D/13 inherited, n = 6, +2.1 (+/-2.4). There was little change in any category if the few cases diagnosed prenatally were included. Only the value for the G/21 mutants is significantly different from zero at the 0.05 level. (The results on G/21 mutants in maternal age are consistent with an earlier Japanese report of an increase of about 2 years over the control values.) The distribution of maternal ages suggests that G/21 mutants may be produced both by maternal age-independent and maternal age-dependent components. The data on D/21 mutants, however, do not indicate the negative association with maternal age reported in Japan. Differences between this study and the Japanese study in analyses of controls may explain this slight variation. But in any event both studies reveal no evidence for an increase in maternal age for unbalanced D/21 mutant or D/21 inherited translocations associated with Down syndrome. This is evidence against the hypothesis that relaxed selection during gestation, after recognition of pregnancy, accounts for the maternal age effects of 47, +21. In comparison with the results on Robertsonian translocations, the case-control differences in maternal age in years (and the standard errors of the mean) for 47, +21 for 2148 livebirths was +4.6 (+/-0.2), and for 2354 cases

  16. The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2012-02-01

    AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

  17. Effects of Quercetin on Adiponectin-Mediated Insulin Sensitivity in Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Double-Blind Clinical Trial.

    Science.gov (United States)

    Rezvan, N; Moini, A; Janani, L; Mohammad, K; Saedisomeolia, A; Nourbakhsh, M; Gorgani-Firuzjaee, S; Mazaherioun, M; Hosseinzadeh-Attar, M J

    2017-02-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous, multi-causal, and genetically complex disorder, which is related to the failure in endocrine glands. Adiponectin has been reported to be low in PCOS, even in the absence of adiposity. Quercetin reduces serum glucose, insulin, triglycerides, and cholesterol levels and increases the expression and secretion of adiponectin. The aim of this study was to determine the effect of quercetin on the adiponectin-mediated insulin sensitivity in PCOS patients. Eighty-four women with PCOS were selected and randomly assigned to 2 groups of treatment and control. The treatment group received 1 g quercetin (two 500 mg capsules) daily for 12 weeks, and the control group received placebo. In addition to anthropometric assessments, fasting serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, glucose, insulin, testosterone, LH, and SHBG were also measured at the baseline and at the end of the trial. Quercetin could slightly increase the level of adiponectin by 5.56% as compared to placebo (adjusted p-value=0.001) and HMW adiponectin by 3.9% as compared to placebo (adjusted p-value=0.017), while it reduced the level of testosterone (0.71 ng/dl in quercetin vs. 0.77 ng/dl in placebo; pquercetin vs. 8.68 IU/l in placebo; p=0.009). HOMA-IR levels were also significantly (pquercetin (1.84) group compared to placebo group (2.21). Oral quercetin supplementation was effective in improving the adiponectin-mediated insulin resistance and hormonal profile of women with PCOS.

  18. Beneficial insulin-sensitizing and vascular effects of S15261 in the insulin-resistant JCR:LA-cp rat.

    Science.gov (United States)

    Russell, J C; Ravel, D; Pégorier, J P; Delrat, P; Jochemsen, R; O'Brien, S F; Kelly, S E; Davidge, S T; Brindley, D N

    2000-11-01

    S15261, a compound developed for the oral treatment of type II diabetes, is cleaved by esterases to the fragments Y415 and S15511. The aim was to define the insulin-sensitizing effects of S15261, the cleavage products, and troglitazone and metformin in the JCR:LA-cp rat, an animal model of the obesity/insulin resistance syndrome that exhibits an associated vasculopathy and cardiovascular disease. Treatment of the animals from 8 to 12 weeks of age with S15261 or S15511 resulted in reductions in food intake and body weights, whereas Y415 had no effect. Troglitazone caused a small increase in food intake (P JCR:LA-cp rat. S15261 may thus offer effective treatment for the insulin resistance syndrome and its associated vascular complications.

  19. Zinc, Iron and Vitamins A, C and E Are Associated with Obesity, Inflammation, Lipid Profile and Insulin Resistance in Mexican School-Aged Children

    Directory of Open Access Journals (Sweden)

    Olga Patricia García

    2013-12-01

    Full Text Available The objective of this cross-sectional study was to evaluate the relationship between micronutrient status and obesity, lipids, insulin resistance and chronic inflammation in children. Weight, height, waist circumference and body composition (dual-energy X-ray absorptiometry (DEXA were determined in 197 school-aged children. Lipids, glucose, insulin, C-reactive protein (CRP, zinc, iron and vitamins A, C and E were analyzed in blood. Vitamin C and vitamin E:lipids were negatively associated with Body Mass Index (BMI, waist-to-height ratio (WHR and body and abdominal fat (p < 0.05. Vitamin A was positively associated with BMI, BMI-for-age, WHR and abdominal fat (p < 0.05. Iron and vitamin E:lipids were negatively associated with insulin (p < 0.05. Vitamins A, C and E and iron were negatively associated with CRP (p < 0.05. Interaction analysis showed that children who were overweight and obese who also had low concentrations of vitamin A had higher CRP and lower triglycerides (p < 0.1, children with low vitamin E had significantly lower glucose and triglycerides (p < 0.1 and higher low-density lipoprotein (LDL concentrations (p < 0.05, and children with low zinc concentrations had higher insulin resistance compared with children with adequate weight (p < 0.05. In conclusion, low vitamin C concentration and vitamin E:lipids were associated with obesity. Furthermore, low concentrations of zinc, vitamins A and E in children who were overweight and obese were associated with lipids, inflammation and insulin resistance.

  20. Sick building syndrome: A disease of modern age

    Directory of Open Access Journals (Sweden)

    Nikić Dragana

    2004-01-01

    Full Text Available Sick building syndrome (SBS is a term used to describe situation in building when more than 30% of occupants suffer from various symptoms which tend to increase by severity during the time people spend in "sick" building and disappear when they leave the building. Typical cases of SBS report vague symptoms, which cannot be objectively measured, and sufferers usually show no clinical signs of illness. Symptom heterogeneity suggests that they do not represent a single disorder. The objective of our study was to establish if SBS is present in our town because new buildings have been built lately producing the artificial environment - exclusively artificial lightning and mechanical ventilation. A total of 812 subjects were included in our study. The investigation of SBS was performed by standardized questionnaires to determine the prevalence of symptoms and complaints. Questionnaires were used to collect data on perception of environment conditions and health during the period they work in this building. The subjects were divided in three groups according to sex, level of education and ownership. Our data suggested that the incidence of symptoms was higher in employers than in owners of the offices. Moreover, the prevalence of SBS was very high - up to 74.76%. It is obvious that certain physical, psychological and organizational factors are involved in the incidence of symptoms, but our investigation suggests that physical factor has a dominant role in development of symptoms, particularly low humidity and low air flow. In addition, our judgment is that SBS exists in our city, probably in the whole country and, therefore, it must be investigated properly.

  1. Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome: implications for normal aging and age-dependent neurodegenerative disorders.

    Science.gov (United States)

    Graziotto, John J; Cao, Kan; Collins, Francis S; Krainc, Dimitri

    2012-01-01

    While rapamycin has been in use for years in transplant patients as an antirejection drug, more recently it has shown promise in treating diseases of aging, such as neurodegenerative disorders and atherosclerosis. We recently reported that rapamycin reverses the cellular phenotype of fibroblasts from children with the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). We found that the causative aberrant protein, progerin, was cleared through autophagic mechanisms when the cells were treated with rapamycin, suggesting a new potential treatment for HGPS. Recent evidence shows that progerin is also present in aged tissues of healthy individuals, suggesting that progerin may contribute to physiological aging. While it is intriguing to speculate that rapamycin may affect normal aging in humans, as it does in lower organisms, it will be important to identify safer analogues of rapamycin for chronic treatments in humans in order to minimize toxicity. In addition to its role in HGPS and normal aging, we discuss the potential of rapamycin for the treatment of age-dependent neurodegenerative diseases.

  2. Aging stem cells. A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging.

    Science.gov (United States)

    Zhang, Weiqi; Li, Jingyi; Suzuki, Keiichiro; Qu, Jing; Wang, Ping; Zhou, Junzhi; Liu, Xiaomeng; Ren, Ruotong; Xu, Xiuling; Ocampo, Alejandro; Yuan, Tingting; Yang, Jiping; Li, Ying; Shi, Liang; Guan, Dee; Pan, Huize; Duan, Shunlei; Ding, Zhichao; Li, Mo; Yi, Fei; Bai, Ruijun; Wang, Yayu; Chen, Chang; Yang, Fuquan; Li, Xiaoyu; Wang, Zimei; Aizawa, Emi; Goebl, April; Soligalla, Rupa Devi; Reddy, Pradeep; Esteban, Concepcion Rodriguez; Tang, Fuchou; Liu, Guang-Hui; Belmonte, Juan Carlos Izpisua

    2015-06-05

    Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1α and nuclear lamina-heterochromatin anchoring protein LAP2β. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.

  3. Longitudinal changes in insulin sensitivity and body composition of small-for-gestational-age adolescents after cessation of growth hormone treatment

    OpenAIRE

    Willemsen, Ruben; Hokken-Koelega, Anita

    2008-01-01

    textabstractContext: GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, β-cell function, and body composition change over time after stopping GH treatment. Objective: Our objective was to investigate longitudinal changes in Si, β-cell function, and body composition after cessation of long-term GH treatment. Design and Patients: We cond...

  4. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan;

    2013-01-01

    Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage......, molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  5. COMPUTER EYE SYNDROME IN CHILDREN AGED 3 TO 6 YEARS

    Directory of Open Access Journals (Sweden)

    Krasina P. Valcheva

    2016-03-01

    Full Text Available Purpose: To detect visual disturbances, major symptoms and relationship between them in children between the ages of 3 and 6 years, who spend some time in front of a computer. Material/Methods: In the present study 2823 children attending 23 kindergartens in the city of Pleven, were given inquiry cards. Those with completed questionnaires were examined for visual acuity and convergence. In cases with low vision the children were invited for a detailed eye examination in the Eye Clinic at the University Hospital "Dr George Stranski" - Pleven. Results: A total of 2332 children responded and were examined (1174 girls and 1158 boys. The age of children is from 3 to 6 years. We found 303 children with subjective complaints in a close work, 163 with low vision and 18 with impaired convergence. Regarding the duration of stay in front of a computer – 159 children stay over 3 hours a day in front of video display, 1228 children spend about 1 hour a day in front of a computer and 945 children do not play on a computer. Conclusion: Nowadays more and more children use computers for recreational purposes at home. From our study it became clear that preschool children overuse their stay in front of computer.

  6. Di-(2-ethylhexyl phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.

    Directory of Open Access Journals (Sweden)

    Arianna Smerieri

    Full Text Available Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl phthalate (DEHP in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP, were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

  7. Race- and sex-specific associations of parental education with insulin resistance in middle-aged participants: the CARDIA study.

    Science.gov (United States)

    Tamayo, Teresa; Jacobs, David R; Strassburger, Klaus; Giani, Guido; Seeman, Teresa E; Matthews, Karen; Roseman, Jeffrey M; Rathmann, Wolfgang

    2012-05-01

    Low childhood socioeconomic status (SES) has been linked with insulin resistance (HOMA-IR) in adulthood. Our aim was to examine if maternal and paternal education, as indicators of childhood SES, equally contributed to increased HOMA-IR in later life. Of 5,115 adults from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study aged 18-30 years in 1985-1986, data on 1,370 females and 1,060 males with baseline and 20 year follow-up data were used to estimate associations of maternal and paternal education with HOMA-IR, adjusting for personal education, BMI, lipids, blood pressure, and lifestyle factors. Parental education was determined as high with ≥ 12 years of schooling and classified as both high, only mother high, only father high, both low education. Distinct combinations of maternal and paternal education were associated with HOMA-IR across race and sex groups. Lowest year 20 HOMA-IR in European American (EA) females occurred when both parents were better educated, but was highest when only the father had better education. HOMA-IR was lowest in African American (AA) participants when the mother was better educated but the father had less education, but was highest when both parents were better educated. Parental education was unrelated to HOMA-IR in EA males. Associations of parental education with HOMA-IR are seen in AA females, AA males, and EA females but not in EA males. The distinct combinations of parental education and their associations with HOMA-IR especially in AA participants need to be addressed in further research on health disparities.

  8. The Relationship between Adiposity and Insulin Sensitivity in African Women Living with the Polycystic Ovarian Syndrome: A Clamp Study

    Science.gov (United States)

    Dohbit, Sama; Tchana-Sinou, Mycilline; Foumane, Pascal; Donfack, Olivier Trésor; Doh, Anderson S.

    2016-01-01

    Objectives. We aimed to assess the variation of insulin sensitivity in relation to obesity in women living with PCOS in a sub-Sahara African setting. Methods. We studied body composition, insulin sensitivity, and resting energy expenditure in 14 PCOS patients (6 obese and 8 nonobese) compared to 10 matched nonobese non-PCOS subjects. Insulin sensitivity was assessed using the gold standard 80 mU/m2/min euglycemic-hyperinsulinemic clamp and resting energy expenditure was measured by indirect calorimetry. Results. Insulin sensitivity adjusted to lean mass was lowest in obese PCOS subjects and highest in healthy subjects (11.2 [10.1–12.4] versus 12.9 [12.1–13.8] versus 16.6 [13.8–17.9], p = 0.012); there was a tendency for resting energy expenditure adjusted for total body mass to decrease across the groups highest in obese PCOS subjects (1411 [1368–1613] versus 1274 [1174–1355] versus 1239 [1195–1454], p = 0.306). Conclusion. In this sub-Saharan population, insulin resistance is associated with PCOS per se but is further aggravated by obesity. Obesity did not seem to be explained by low resting energy expenditure suggesting that dietary intake may be a determinant of the obesity in this context. PMID:27672393

  9. Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects.

    Science.gov (United States)

    Nilsson, Anne C; Johansson-Boll, Elin V; Björck, Inger M E

    2015-09-28

    Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H₂ excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.

  10. Aging, female sex, migration, elevated HDL-C, and inflammation are associated with prevalence of metabolic syndrome among African bank employees

    Directory of Open Access Journals (Sweden)

    Gombet T

    2012-06-01

    Full Text Available Thierry Gombet,1 Benjamin Longo-Mbenza,2 Bertrand Ellenga-Mbolla,1 Meo Stephane Ikama,3 Etienne Mokondjimobe,4 Gisele Kimbally-Kaky,3 Jean-Louis Nkoua,31Emergency Department, University Hospital Center of Brazzaville, Brazzaville, Congo; 2Faculty of Health Sciences, Walter Sisulu University, Mthatha, Eastern Cape, South Africa; 3Department of Cardiology and Internal Medicine, University Hospital Center of Brazzaville, Brazzaville, Congo; 4Laboratory of Biochemistry and Pharmacology, Faculty of Health Sciences, Brazzaville, CongoBackground: The objective of this study was to compare four different criteria for diagnosing metabolic syndrome (MS and to correlate sociodemographic data, liver enzymes, lipids, inflammation, and insulin resistance with MS definitions.Methods: This cross-sectional study included a random number of 126 African bank employees from Brazzaville, Congo.Results: The prevalence of MS varied according to the different definitions used: 4.8% under World Health Organization (WHO criteria, 8.7% under the National Cholesterol Education Program Adult Treatment Panel III (NECP-ATPIII criteria, 14.3% under the International Diabetes Federation (IDF for Europe, and 15.9% by the IDF for Central Africa. According to the IDF, specific cutoff points for the erythrocyte sedimentation rate, ≥13 mm at first hour and ≥30 mm at second hour, defined MS for Central Africa. The best agreement was observed between the IDF for Europe and the IDF for Central Africa (Kappa = 0.938; P < 0.0001 criteria. The worst agreements were between the WHO and IDF for Central Africa (Kappa = 0.419; P < 0.0001 criteria and between the WHO and IDF for Europe (Kappa = 0.462; P < 0.0001 criteria. The NECP-ATPIII criteria did not agree with either the IDF for Europe or the IDF for Central Africa criteria. There was a significant relationship between female sex, aging, elevated liver enzymes, elevated phospholipids, high homeostasis model assessment of insulin

  11. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... and insulin stimulated glucose uptake in both the soleus and extensor digitorum longus muscle, coinciding with reduced insulin signaling at the level of Akt (pSer473 and pThr308), TBC1D1 (pThr590) and TBC1D4 (pThr642). In contrast to our hypothesis, the impact of ageing and high fat diet on insulin action...

  12. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel;

    2014-01-01

    was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...

  13. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

    DEFF Research Database (Denmark)

    Magnussen, Line V; Glintborg, Dorte; Hermann, Pernille;

    2016-01-01

    AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy....... MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM...

  14. Leptin, insulin and thyroid hormones in a cohort of Egyptian obese Down syndrome children: a comparative study

    OpenAIRE

    Yahia Sohier; EL-farahaty Reham M; El-Hawary Amany K; El-hussiny Mona A; Abdel-maseih Hanaa; El-Dahtory Faeza; El-Gilany Abdel-Hady

    2012-01-01

    Abstract Background Obesity is a major worldwide health problem. It is commonly observed in Down syndrome individuals than in the general population. The reason for increased risk of obesity in DS is unclear. The current study was designed to clarify differences in some obesity- related hormones in a group of prepubertal Down syndrome children. Methods Thirty six Egyptian children with Down syndrome were enrolled in this study, divided according to their body mass index (BMI) into 23 obese an...

  15. Resistência à insulina em mulheres com síndrome dos ovários policísticos modifica fatores de risco cardiovascular Cardiovascular risk markers in polycystic ovary syndrome in women with and without insulin resistance

    Directory of Open Access Journals (Sweden)

    Wellington de Paula Martins

    2009-03-01

    Full Text Available OBJETIVO: avaliar se a presença de resistência à insulina (RI modifica fatores de risco cardiovascular em mulheres com síndrome dos ovários policísticos (SOP. MÉTODOS: estudo transversal no qual 60 mulheres com SOP, com idade entre 18 e 35 anos e sem uso de hormônios, foram avaliadas. A RI foi avaliada por meio do quantitative insulin sensitivity check index (QUICKI. RI foi definida como QUICKI PURPOSE: to evaluate whether the presence of insulin resistance (IR alters cardiovascular risk factors in women with polycystic ovary syndrome (POS. METHODS: transversal study where 60 POS women with ages from 18 to 35 years old, with no hormone intake, were evaluated. IR was assessed through the quantitative insulin sensitivity check index (QUICKI and defined as QUICKI <0.33. The following variables have been compared between the groups with or without IR: anthropometric (weight, height, waist circumference, arterial blood pressure, cardiac frequency, laboratorial (homocysteine, interleucines-6, factor of tumoral-α necrosis, testosterone, fraction of free androgen, total cholesterol and fractions, triglycerides, C reactive protein, insulin, glucose, and ultrasonographical (distensibility and carotid intima-media thickness, dilation mediated by the brachial artery flux. RESULTS: Eighteen women (30% presented IR and showed significant differences in the following anthropometric markers, as compared to the women without IR (POS with and without IR respectively: body mass index (35.56±5.69 kg/m² versus 23.90±4.88 kg/m², p<0.01, waist (108.17±11.53 versus 79.54±11.12 cm, p<0.01, systolic blood pressure (128.00±10.80 mmHg versus 114.07±8.97 mmHg, p<0.01, diastolic blood pressure (83.67±9.63 mmHg versus 77.07±7.59 mmHg, p=0.01. It has also been observed significant differences in the following laboratorial markers: triglycerides (120.00±56.53 mg/dL versus 77.79±53.46 mg/dL, p=0.01, HDL (43.06±6.30 mg/dL versus 40.45±10.82 mg/dL, p=0

  16. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

  17. The Research Progress in Insulin Resistance in Polycystic Ovary Syndrome%多囊卵巢综合征胰岛素抵抗的新进展

    Institute of Scientific and Technical Information of China (English)

    李曌

    2011-01-01

    With the morbidity of 5%~10% in premenopausal women, polycystic ovary syndrome (PCOS) is an exceptionally commen disorder. Its features are chronic anovulation or few ovulations,polycystic ovaries increase in size and hyperandrogenism. In addition,it is also characterized by insulin resistance (IR) and β-cell dysfunction. The conception rate of patients with PCOS is fallen, and patient's prevalence rate of spontaneous abortion during pregnancy and gestatianal diabetes is higher than the normal persons. Besides,these patients are at higer risk of suffering from endometrial carcinoma .Some result from several recent studies, showed that patient's incidence of metabolic syndrome (MS) was increased. Metabolic syndrome has a significant relationship with cardiovascular diseases and IR. At present,many scholars have made extensive researches on the impact of IR and PCOS,pointing out that it is effective to improve PCOS patients'endocrine condition and their reproduction by ameliorate their insulin resistance. Lifestyle adjustment can be a efficient measure to achieve this aim,besides,oral hypoglycemic agents can also be an effective method to treat the insulin resistance in PCOS.%多囊卵巢综合征((PCOS)是青春期及育龄妇女最常见的内分泌和代谢紊乱性疾病,其发病率占育龄妇女的5%-10%.PCOS的基本特征为长期不排卵或稀发排卵、卵巢多囊性增大和高雄激素血症等,此外还表现有胰岛素抵抗(IR)及胰岛β细胞功能失调.PCOS患者妊娠率降低,妊娠期自然流产、妊娠期糖尿病的患病率亦较普通人群高,同时子宫内膜癌发病风险增高.PCOS患者代谢综合征的发病率升高,后者与心血管疾病风险紧密相连,并与IR有密切关系.目前许多学者对PCOS患者的IR做了大量的研究,提示改善PCOS 的IR可改善内分泌及生殖功能,而改善生活方式是改善患者IR的有效手段.口服降糖药已成为治疗PCOS 的IR的有效方法之一.

  18. LMNA-Associated Cardiocutaneous Progeria: a Novel Autosomal Dominant Premature Aging Syndrome with Late Onset

    Science.gov (United States)

    Kane, Megan S.; Lindsay, Mark E.; Judge, Daniel P.; Barrowman, Jemima; Rhys, Colette Ap; Simonson, Lisa; Dietz, Harry C.; Michaelis, Susan

    2013-01-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a well-characterized premature aging disorder caused by mutations in LMNA, the gene encoding the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. Emerging evidence indicates that LMNA-linked progerias can be grouped into two classes: 1) the processing-deficient, early onset “typical” progerias (e.g. HGPS), and 2) the processing-proficient “atypical” progeria syndromes (APS) that are later in onset. Here we describe a novel progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that causes LCPS is a heterozygous missense mutation resulting in an amino acid substitution (D300G) in the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors (FTIs), as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease. PMID:23666920

  19. LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset.

    Science.gov (United States)

    Kane, Megan S; Lindsay, Mark E; Judge, Daniel P; Barrowman, Jemima; Ap Rhys, Colette; Simonson, Lisa; Dietz, Harry C; Michaelis, Susan

    2013-07-01

    Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disorder caused by mutations in LMNA, which encodes the nuclear scaffold proteins lamin A and C. In HGPS and related progerias, processing of prelamin A is blocked at a critical step mediated by the zinc metalloprotease ZMPSTE24. LMNA-linked progerias can be grouped into two classes: (1) the processing-deficient, early onset "typical" progerias (e.g., HGPS), and (2) the processing-proficient "atypical" progeria syndromes (APS) that are later in onset. Here we describe a previously unrecognized progeria syndrome with prominent cutaneous and cardiovascular manifestations belonging to the second class. We suggest the name LMNA-associated cardiocutaneous progeria syndrome (LCPS) for this disorder. Affected patients are normal at birth but undergo progressive cutaneous changes in childhood and die in middle age of cardiovascular complications, including accelerated atherosclerosis, calcific valve disease, and cardiomyopathy. In addition, the proband demonstrated cancer susceptibility, a phenotype rarely described for LMNA-based progeria disorders. The LMNA mutation that caused LCPS in this family is a heterozygous c.899A>G (p.D300G) mutation predicted to alter the coiled-coil domain of lamin A/C. In skin fibroblasts isolated from the proband, the processing and levels of lamin A and C are normal. However, nuclear morphology is aberrant and rescued by treatment with farnesyltransferase inhibitors, as is also the case for HGPS and other laminopathies. Our findings advance knowledge of human LMNA progeria syndromes, and raise the possibility that typical and atypical progerias may converge upon a common mechanism to cause premature aging disease.

  20. Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wascher, T C; Wölkart, G; Russell, J C; Brunner, F

    2000-05-01

    Capillary endothelial cells are thought to limit the transport of insulin across the endothelium, resulting in attenuated insulin action at target sites. Whether endothelial insulin transport is altered in dysglycemic insulin-resistant states is not clear and was therefore investigated in the JCR:LA-cp corpulent male rat, which exhibits the metabolic syndrome of obesity, insulin resistance, hyperlipidemia, and hyperinsulinemia. Lean littermates that did not develop these alterations served as controls. Animals of both groups were normotensive (mean arterial pressure 136+/-2 mmHg). Hearts from obese and lean rats aged 7 (n = 6) or 18 (n = 8) weeks were perfused in vitro at 10 ml/min per gram wet wt over 51 min with Krebs-Henseleit buffer containing 0.1 or 0.5 U human insulin/l (equivalent to 0.6 and 3 nmol/l). Interstitial fluid was collected using a validated method, and interstitial insulin was determined with a radioimmunoassay. At 0.1 U/l, insulin transfer velocity was similar in both experimental groups (half-times of transfer: 11+/-0.2 min in obese and 18+/-4 min in lean rats; NS), but at 0.5 U/l, the respective half-times were 7+/-1 min in lean and 13+/-2 min in obese rats (P < 0.05). The steady-state level of insulin in the interstitium was 34+/-1% of the vascular level at 0.1 U/l and reached the vascular level (102+/-2%) at 0.5 U/l in both lean and obese rats. In rats aged 18 weeks, the half-times of insulin transfer were 31+/-2 and 14+/-l min in obese rats and 10+/-0.3 and 7+/-0.3 min in lean rats (P < 0.05). Again, interstitial steady-state levels were similar in both groups. Finally, postprandial insulin dynamics were simulated over a period of 120 min with a peak concentration of 0.8 U/l in rats aged 27 weeks (n = 4). The maximal interstitial level was 0.38+/-0.02 U/l in lean rats and 0.24+/-0.02 U/l in obese rats (P < 0.05), and a similar difference was noted throughout insulin infusion (areas under the transudate concentration-time curves: 17 and 11 U

  1. INCIDENCE OF STUTTERING IN SCHOOL-AGE CHILDREN WITH DOWN SYNDROME

    Directory of Open Access Journals (Sweden)

    Nevzeta SALIHOVIĆ

    2012-03-01

    Full Text Available The main purpose of this study was to examine the incidence (frequency and stuttering severity in the school-age children with Down syndrome. The sample was consisted of 37 school-age children with Down syndrome, both male and female. The study was conducted in the following institutions: Institute of Special Education and Rehabilitation for Children with Intellectual Disabilities "Mjedenica"; Centre for Education, Training and Employment of Mentally Retarded Children, Children with Autism and Cerebral palsy "Vladimir Nazor" in Sarajevo; Primary School of Special Education „Zenica“; Primary school "Kovačići" Sarajevo; "Association of United Civic Actions – DUGA" in Sarajevo; and The Association "Be my friend" in Ilijaš. All of the subjects were individually examined. The results showed that 13,51 % of the children with Down syndrome stuttered, and the total result of stuttering severity indicates a moderate stuttering. These results show that children with Down syndrome should be enrolled intensively in speech therapy in order to help them overcome their stuttering, to facilitate their everyday communication and to teach them how to cope with stuttering.

  2. A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice

    Directory of Open Access Journals (Sweden)

    Raquel Riquelme

    2010-06-01

    Full Text Available Insulin-like growth factor-I (IGF-I belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to

  3. A Comparative Study of Age-Related Hearing Loss in Wild Type and Insulin-Like Growth Factor I Deficient Mice

    Science.gov (United States)

    Riquelme, Raquel; Cediel, Rafael; Contreras, Julio; Lourdes, Rodriguez-de la Rosa; Murillo-Cuesta, Silvia; Hernandez-Sanchez, Catalina; Zubeldia, Jose M.; Cerdan, Sebastian; Varela-Nieto, Isabel

    2010-01-01

    Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or

  4. Concurrent Therapy with a Low-carbohydrate Diet and Miglitol Remarkably Improved the Postprandial Blood Glucose and Insulin Levels in a Patient with Reactive Hypoglycemia due to Late Dumping Syndrome.

    Science.gov (United States)

    Hirose, Sachie; Iwahashi, Yasuyuki; Seo, Akane; Sumiyoshi, Michitaka; Takahashi, Tetsuya; Tamori, Yoshikazu

    2016-01-01

    Reactive hypoglycemia induced by late dumping syndrome is often observed after gastrectomy. However, no effective therapy has yet been fully established. We herein describe a case in which concurrent therapy with a low-carbohydrate diet using low-glycemic-index food and an alpha-glucosidase inhibitor, miglitol, very effectively ameliorated the postprandial fluctuations in the blood glucose and plasma insulin levels in a patient with reactive hypoglycemia due to late dumping syndrome following total gastrectomy. The administration of miglitol under a low-carbohydrate diet using low-glycemic-index food may therefore be an ideal treatment for reactive hypoglycemia due to late dumping syndrome.

  5. Insulin resistance in Saudi postmenopausal women with and without metabolic syndrome and its association with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Eman M. Alissa, PhD

    2015-03-01

    Conclusions: These observations suggest that hypovitaminosis D may be associated with the risk of developing metabolic syndrome. Interrelationships between IR, metabolic syndrome, and hypovitaminosis D are of particular interest in Saudi population, given the high prevalence of these conditions in this region.

  6. The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

    NARCIS (Netherlands)

    Snel, M.; Sleddering, M.A.; Pijl, H.; Nieuwenhuizen, W.F.; Frölich, M.; Havekes, L.M.; Romijn, J.A.; Jazet, I.M.

    2010-01-01

    Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary suppleme

  7. Metabolic acidosis-induced insulin resistance and cardiovascular risk.

    Science.gov (United States)

    Souto, Gema; Donapetry, Cristóbal; Calviño, Jesús; Adeva, Maria M

    2011-08-01

    Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosis worsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.

  8. Common variants modify the age of onset for basal cell carcinomas in Gorlin syndrome.

    Science.gov (United States)

    Yasar, Binnaz; Byers, Helen J; Smith, Miriam J; Lear, John; Oudit, Deemesh; Bholah, Zaynab; Roberts, Stephen A; Newman, William G; Evans, D Gareth

    2015-05-01

    Gorlin syndrome is an autosomal dominant disorder, characterized by multiple early-onset basal cell carcinomas (BCCs) and jaw keratocysts. Through association studies in cohorts of sporadic BCC, nine genetic variants have previously been identified to increase the risk of BCC. The nine SNPs were genotyped by Taqman allelic discrimination in 125 individuals with Gorlin syndrome. Kaplan-Meier survival curves and Cox proportional-Hazard regression analysis were applied to determine the association between genotypes and age of first BCC in individuals with Gorlin syndrome. The p.(Arg151Cys) variant in MC1R (rs1805007) was associated with an earlier median age of onset of BCC of 27 years (95% CI: 20-34) compared with 34 years (95% CI: 30-40) for wild-type individuals (hazard ratio (HR)=1.64, 95% CI: 1.04-2.58, P=0.034). The risk allele of the variant at the chromosome 5p15 locus encompassing TERT-CLPTM1L (rs401681) was also associated with an earlier median onset of BCC, 31 years (95% CI: 28-37) compared with 41 years (95% CI: 32-48, HR=1.44, 95% CI: 1.08-1.93, P=0.014). In individuals with a risk allele at either rs1805007 or rs401681 the median time to BCC was 31 years of age (95% CI: 28-34) compared with 44 years of age (95% CI: 38-53) in wild-type individuals (HR=2.48, 95% CI: 1.47-4.17, P=0.0002). Our findings may have implications for future personalized risk estimates and BCC screening strategies in individuals with Gorlin syndrome.

  9. Association between 25-hydroxyvitamin D and metabolic syndrome in middle-aged and elderly population

    Institute of Scientific and Technical Information of China (English)

    林寰东

    2013-01-01

    Objective To explore the relationship between vitamin D and metabolic syndrome.Methods A total of 536subjects aged over 45 years old from Shanghai Changfeng community were included.A standard questionnaire,anthropometric parameters,and blood analysis,including lipid,fasting plasma glucose,2 h plasma glucose after oral glucose tolerance test,25-hydroxyvitamin D[25 (OH) D],and parathyroid hormone (PTH) were conducted.Bone mineral content was examined using dual energy

  10. Oxidative Stress and Mitochondrial Dysfunction in Down’s Syndrome: Relevance to Aging and Dementia

    OpenAIRE

    Coskun, Pinar E; Jorge Busciglio

    2012-01-01

    Genome-wide gene deregulation and oxidative stress appear to be critical factors determining the high variability of phenotypes in Down’s syndrome (DS). Even though individuals with trisomy 21 exhibit a higher survival rate compared to other aneuploidies, most of them die in utero or early during postnatal life. While the survivors are currently predicted to live past 60 years, they suffer higher incidence of age-related conditions including Alzheimer’s disease (AD). This paper is centered on...

  11. Brain aging and metabolic syndrome: a study in Cenischia Valley (Piedmont).

    OpenAIRE

    Marianna Rinaldi; Giuseppe Graffi; Salvatore Gallone; Emma Rabino Massa

    2011-01-01

    The Metabolic Syndrome (MetS) is a set of conditions, each of which represents a risk factor for cardiovascular disease (central obesity, hyperglycemia, dyslipidemia and hypertension). Recent studies have identified an association between MetS and increased risk of dementia (Vascular Dementia and Late Onset Alzheimer's Disease ). The purpose of our research is the study of brain aging and cognitive decline in a sample of elderly people (n=200) belonging to a rural alpine community, in r...

  12. Scopoletin Protects against Methylglyoxal-Induced Hyperglycemia and Insulin Resistance Mediated by Suppression of Advanced Glycation Endproducts (AGEs Generation and Anti-Glycation

    Directory of Open Access Journals (Sweden)

    Wen-Chang Chang

    2015-02-01

    Full Text Available Recently, several types of foods and drinks, including coffee, cream, and cake, have been found to result in high methylglyoxal (MG levels in the plasma, thus causing both nutritional and health concerns. MG can be metabolized by phase-II enzymes in liver through the positive regulation of nuclear factor-erythroid 2-related factor 2 (Nrf2. In this study, we investigated the ability of scopoletin (SP to protect against MG-induced hyperglycemia and insulin resistance. Recently, SP was shown to be a peroxisome proliferator-activated receptor-γ activator to elevate insulin sensitivity. We investigated the effects of oral administration of SP on the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats to understand the potential mechanism of scopoletin for diabetes protection. Our results suggested that SP activated Nrf2 by Ser40 phosphorylation, resulting in the metabolism of MG into d-lactic acid and the inhibition of AGEs generation, which reduced the accumulation of AGEs in the livers of MG-induced rats. In this manner, SP improved the results of the oral glucose tolerance test and dyslipidemia. Moreover, SP also increased the plasma translocation of glucose transporter-2 and promoted Akt phosphorylation caused by insulin treatment in MG-treated FL83B hepatocytes. In contrast, SP effectively suppressed protein tyrosine phosphatase 1B (PTP1B expression, thereby alleviating insulin resistance. These findings suggest that SP acts as an anti-glycation and anti-diabetic agent, and thus has therapeutic potential for the prevention of diabetes.

  13. Hiperandrogenismo e pele: síndrome do ovário policístico e resistência periférica à insulina Hyperandrogenism and skin: polycystic ovary syndrome and peripheral insulin resistance

    Directory of Open Access Journals (Sweden)

    Samira Yarak

    2005-08-01

    Full Text Available A síndrome do ovário policístico é distúrbio endócrino feminino, extremamente comum na idade reprodutiva. Caracteriza-se por anormalidades menstruais, hiperandrogenismo e/ou hiperandrogenemia. A principal alteração na fisiopatologia é desconhecida. Entretanto, parece que a resistência à insulina, o hiperandrogenismo e a alteração na dinâmica das gonadotropinas são os mais importantes mecanismos fisiopatológicos envolvidos. As características clínicas mais freqüentes da síndrome do ovário policístico estão relacionadas com a unidade pilossebácea, como hirsutismo, acne, seborréia e alopecia. Desse modo, o dermatologista pode ser responsável pelo diagnóstico precoce da síndrome, evitando o retardo na instituição de medidas terapêutico-preventivas. Atualmente, as drogas recomendadas para as manifestações cutâneas da síndrome do ovário policístico são os contraceptivos orais conjugados, antiandrógenos e sensibilizantes de insulina e, além disso, é geralmente recomendada a modificação no estilo de vida. Trata-se de artigo de revisão sobre diagnóstico, fisiopatologia e tratamento da síndrome do ovário policístico. Os autores enfatizam que o conhecimento da fisiopatologia dessa síndrome, principalmente pelos dermatologistas, é fundamental para seu tratamento preventivo, nas diferentes fases da vida da mulher.The polycystic ovary syndrome is an extremely common endocrine disorder in women of chilbearing age. It is characterized by menstrual disturbance, hyperandrogenism and/or hyperandrogenemia. The primary pathophysiological defect is unknown, but important characteristics include insulin resistance, androgen excess and impaired gonadotropin dynamics. The most frequent clinical characteristics of polycystic ovary syndrome are associated with the pilosebaceous unit, such as hirsutism, acne, seborrhea and alopecia. Thus, the dermatologist may be responsible for making an early diagnosis of the syndrome

  14. Metabolic Syndrome in Italian Obese Children and Adolescents: Stronger Association with Central Fat Depot than with Insulin Sensitivity and Birth Weight

    Directory of Open Access Journals (Sweden)

    Claudia Brufani

    2011-01-01

    Full Text Available Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD were associated with metabolic syndrome (MetS in children and adolescents. Methods. A total of 439 Italian obese children and adolescents (5–18 years were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry, insulin sensitivity (ISI, and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS. Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%. In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest predictor of MetS, with ISI similarly influencing the probability of MetS in the two groups and birth weight being negatively associated to MetS only in pubertal individuals. Neither FHD nor degree of fatness was a significant predictor of MetS. Conclusion. Simple clinical parameters like increased abdominal adiposity and low birth weight could be useful tools to identify European obese adolescents at risk for metabolic complications.

  15. Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down's syndrome.

    Science.gov (United States)

    Park, E; Alberti, J; Mehta, P; Dalton, A; Sersen, E; Schuller-Levis, G

    2000-04-01

    Down's syndrome (DS) has been considered a model of accelerated aging and of Alzheimer's disease. We investigated immunologic functions using peripheral blood leukocytes in order to correlate the production of cytokines and development of neuropathological changes of Alzheimer type in aged persons with DS. Cytokine production (IL-1beta, IL-2, IL-6, IL-8, and TNF-alpha), phytohemagglutinin (PHA)-stimulated proliferation of nonadherent monocytes, and superoxide anion production from polymorphonuclear leukocytes were measured. PHA-stimulated proliferation in aged individuals (>30 years old) with DS was significantly lower than that of age- and sex-matched controls (DS vs control, 55,707+/-5810 vs 88,310+/-6994 cpm, P < 0.001). PHA-stimulated IL-2 production was also significantly decreased in aged individuals with DS (DS vs control, 7.1+/-2.1 vs 10.7+/-1.3 ng/ml). Interestingly, the decrease of proliferation and IL-2 production in aged males with DS is significantly greater than in aged women with DS. PHA-stimulated proliferation and IL-2 production of nonadherent monocytes in females was not significantly reduced. IL-1beta production by LPS-activated adherent monocytes was significantly decreased in older adults with DS compared with non-DS controls. Other immune parameters measured in DS were not significantly different from that of age-matched controls. We conclude that there is partial impairment of T lymphocytes in aged persons with DS that is significantly greater in males than in females.

  16. Age as a Risk Factor for Burnout Syndrome in Nursing Professionals: A Meta-Analytic Study.

    Science.gov (United States)

    Gómez-Urquiza, José L; Vargas, Cristina; De la Fuente, Emilia I; Fernández-Castillo, Rafael; Cañadas-De la Fuente, Guillermo A

    2017-04-01

    Although past research has highlighted the possibility of a direct relationship between the age of nursing professionals and burnout syndrome, results have been far from conclusive. The aim of this study was to conduct a wider analysis of the influence of age on the three dimensions of burnout syndrome (emotional exhaustion, depersonalization, and personal accomplishment) in nurses. We performed a meta-analysis of 51 publications extracted from health sciences and psychology databases that fulfilled the inclusion criteria. There were 47 reports of information on emotional exhaustion in 50 samples, 39 reports on depersonalization for 42 samples, and 31 reports on personal accomplishment in 34 samples. The mean effect sizes indicated that younger age was a significant factor in the emotional exhaustion and depersonalization of nurses, although it was somewhat less influential in the dimension of personal accomplishment. Because of heterogeneity in the effect sizes, moderating variables that might explain the association between age and burnout were also analyzed. Gender, marital status, and study characteristics moderated the relationship between age and burnout and may be crucial for the identification of high-risk groups. More research is needed on other variables for which there were only a small number of studies. Identification of burnout risk factors will facilitate establishment of burnout prevention programs for nurses. © 2016 Wiley Periodicals, Inc.

  17. MECHANISMS OF PREMATURE VASCULAR AGING IN CHILDREN WITH HUTCHINSON-GILFORD PROGERIA SYNDROME

    Science.gov (United States)

    Gerhard-Herman, Marie; Smoot, Leslie B.; Wake, Nicole; Kieran, Mark W.; Kleinman, Monica E.; Miller, David T.; Schwartzman, Armin; Giobbie-Hurder, Anita; Neuberg, Donna; Gordon, Leslie B.

    2011-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare, segmental premature aging syndrome of accelerated atherosclerosis and early death from myocardial infarction or stroke. This study sought to establish comprehensive characterization of the fatal vasculopathy in HGPS and its relevance to normal aging. We performed cardiovascular assessments at a single clinical site on the largest prospectively studied cohort to date. Carotid-femoral pulse wave velocity was dramatically elevated (mean 13.00±3.83 m/s). Carotid duplex ultrasound echobrightness, assessed in predefined tissue sites as a measure of arterial wall density, was significantly greater than age- and gender-matched controls in the intima-media (P<0.02), near adventitia (P<0.003) and deep adventitia (P<0.01), as was internal carotid artery mean flow velocity (p<0.0001). Ankle-brachial indices were abnormal in 78% of patients. Effective disease treatments may be heralded by normalizing trends of these noninvasive cardiovascular measures. The data demonstrates that, along with peripheral vascular occlusive disease, accelerated vascular stiffening is an early and pervasive mechanism of vascular disease in HGPS. There is considerable overlap with cardiovascular changes of normal aging, which reinforces the view that defining mechanisms of cardiovascular disease in HGPS provides a unique opportunity to isolate a subset of factors influencing cardiovascular disease in the general aging population. PMID:22083160

  18. Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.

    Science.gov (United States)

    Wolters, Pamela L; Gropman, Andrea L; Martin, Staci C; Smith, Michaele R; Hildenbrand, Hanna L; Brewer, Carmen C; Smith, Ann C M

    2009-10-01

    Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention.

  19. Placement, Relocation and End of Life Issues in Aging Adults with and without Down's Syndrome: A Retrospective Study

    Science.gov (United States)

    Patti, P.; Amble, K.; Flory, M.

    2010-01-01

    Background: Aging adults with Down's syndrome (DS) experience more relocations and other life events than adults with intellectual disabilities aged 50 and older without DS. Age-related functional decline and the higher incidence of dementia were implicated as the contributing factors that led to relocation and nursing home placement. Method: A…

  20. Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging [v1; ref status: indexed, http://f1000r.es/4fk

    Directory of Open Access Journals (Sweden)

    Oge Arum

    2014-10-01

    Full Text Available The correlation of physiological sensitivity to insulin (vis-à-vis glycemic regulation and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity. The growth hormone receptor/ binding protein gene-disrupted (GHR-KO mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L. counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice.

  1. Insulin pumps in pregnancy: using technology to achieve normoglycemia in women with diabetes.

    Science.gov (United States)

    Castorino, Kristin; Paband, Rashid; Zisser, Howard; Jovanovič, Lois

    2012-02-01

    Poorly controlled diabetes before conception and during pregnancy among women with pre-existing diabetes can cause major birth defects and spontaneous abortions, as wells as abnormal fetal growth and development including an offspring who is small or large for gestational age, or predisposed to obesity, type 2 diabetes, and metabolic syndrome in his/her lifetime. Conversely, for a woman with pre-existing diabetes, optimizing blood glucose levels before and during early pregnancy can reduce these risks dramatically. As insulin pump technology has evolved, continuous subcutaneous insulin infusion has become a safe and reliable method for treating diabetes during pregnancy. Although pump therapy is often preferred by patients and some experts, insulin pumps have not yet been shown to be superior to multiple daily injections of insulin during pregnancy. In this review of the literature we focus on the use of insulin pumps in the management of diabetes in pregnancy.

  2. Insulin-like growth factor-I raises serum procollagen levels in children and adults with Laron syndrome

    DEFF Research Database (Denmark)

    Klinger, B; Jensen, L T; Silbergeld, A;

    1996-01-01

    OBJECTIVE: Recombinant IGF-I is now available for the treatment of GH insensitivity (Laron syndrome). We have determined the effects of IGF-I on soft connective tissue and bone metabolism in a group of patients with this disorder. PATIENTS AND DESIGN: Thirteen patients with Laron syndrome (LS) (8...... levels increased from 3.6 +/- 0.9 to 5.5 +/- 2.2 micrograms/l (P Laron syndrome patients and their rise during replacement therapy with IGF-I provide evidence...

  3. Age-dependent nongenetic influences of birth weight and adult body fat on insulin sensitivity in twins

    DEFF Research Database (Denmark)

    Monrad, Rikke Nygaard; Grunnet, Louise Groth; Rasmussen, Eva Lind

    2009-01-01

    We hypothesized a nongenetic influence of birth weight (BW) and twin and zygosity status on dual-energy x-ray absorptiometry determined adult total and regional body composition and a quantitative equal, although independent, importance of adult body composition and BW for insulin sensitivity....

  4. Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration

    NARCIS (Netherlands)

    A.C. Lambooij; K.H.M. van Wely (Karel); D.J. Lindenbergh-Kortleve (Dicky); R.W.A.M. Kuijpers (Robert); M. Kliffen (Mike); C.M. Mooy (Cornelia)

    2003-01-01

    textabstractPURPOSE: The insulin-like growth factor (IGF)-I protein is a growth-promoting polypeptide that can act as an angiogenic agent in the eye. The purpose of the current study was to localize the expression of IGF-I and its receptor (IGF-IR) mRNA and IGF-IR protein in situ i

  5. Age, gender, insulin and blood glucose control status alter the risk of ischemic heart disease and stroke among elderly diabetic patients

    Directory of Open Access Journals (Sweden)

    Hattori Yoshiyuki

    2011-10-01

    Full Text Available Abstract Background We analyzed the effects of insulin therapy, age and gender on the risk of ischemic heart disease (IHD and cerebrovascular accident (CVA according to glycemic control. Methods and Results We performed a prospective cohort study (Japan Cholesterol and Diabetes Mellitus Study of type 2 diabetes patients (n = 4014 for 2 years. The primary endpoint was the onset of fatal/non-fatal IHD and/or CVA, which occurred at rates of 7.9 and 7.2 per 1000 person-years, respectively. We divided diabetic patients into four groups based on age (≤ 70 and > 70 and hemoglobin A1C levels (≤ 7.0 and > 7.0%. Multiple regression analysis revealed that IHD was associated with high systolic blood pressure and low HDL-C in patients under 70 years of age with fair glycemic control and was associated with low diastolic blood pressure in the older/fair group. Interestingly, insulin use was associated with IHD in the older/poor group (OR = 2.27, 95% CI = 1.11-5.89; p = 0.026 and was associated with CVA in the older/fair group (OR = 2.09, 95% CI = 1.06-4.25; p = 0.028. CVA was associated with lower HDL-C and longer duration of diabetes in younger/poor glycemic control group. Results by stepwise analysis were similar. Next, patients were divided into four groups based on gender and diabetic control(hemoglobinA1C 7.0%. Multiple regression analysis revealed that IHD was associated with high systolic blood pressure in male/fair glycemic control group, age in male/poor control group, and short duration of diabetic history in females in both glycemic control groups. Interestingly, insulin use was associated with IHD in the male/poor group(OR = 4.11, 95% CI = 1.22-8.12; p = 0.018 and with CVA in the female/poor group(OR = 3.26, 95% CI = 1.12-6.24; p = 0.02. CVA was associated with short duration of diabetes in both female groups. Conclusions IHD and CVA risks are affected by specific factors in diabetics, such as treatment, gender and age. Specifically, insulin

  6. Complementary Therapy in Polycystic Ovary Syndrome

    OpenAIRE

    Aquino, Carmen Imma; Nori, Stefania Lucia

    2014-01-01

    Polycystic Ovary Syndrome (PCOS) is an endocrine disease. PCOS afflicts 5 to 10 % of women of reproductive age. The symptoms are: amenorrhea, oligomenorrhea, hirsutism, obesity, infertility, chronic hyperandrogenic anovulation and acne. Other risk factors aggravate this condition: insulin resistance, obesity, hypertension, dyslipidemia, inflammation and subclinical cardiovascular disease. Anxiety, depression and reduced quality of life are also common. This review highlights the mechanisms an...

  7. Neu-Laxova syndrome in an appropriate for gestational age newborn

    Directory of Open Access Journals (Sweden)

    Dilli Dilek

    2008-01-01

    Full Text Available Neu-Laxova syndrome is a rare lethal congenital disorder involving multiple systems. Intrauterine growth retardation, ichthyosis, microcephaly, abnormal facial findings, and limb contractures are its key features. We present a case of Neu-Laxova syndrome in a male appropriate for gestational age (AGA newborn with characteristic features including ichthyosis, microcephaly, severe ectropion, rudimentary ears, eclabion, limb contractures, and hypoplastic genitalia. The patient was born at 38 weeks of gestation to consanguinous Turkish parents. The mother was a 20-year-old primi gravida with lack of prenatal follow-up. Therefore, the case was diagnosed postnatally, and he died 5 days later. Because of the autosomal recessive inheritance of Neu-Laxova syndrome, in countries with high rates of consanguineous marriage, such as Turkey, physicians have to know this syndrome, and serial prenatal ultrasound examinations with genetic counseling should be performed on pregnant women at high risk. To the best of our knowledge, this is the first case described in an AGA newborn.

  8. Hutchinson-Gilford progeria syndrome as a model for vascular aging.

    Science.gov (United States)

    Brassard, Jonathan A; Fekete, Natalie; Garnier, Alain; Hoesli, Corinne A

    2016-02-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder caused by a de novo genetic mutation that leads to the accumulation of a splicing isoform of lamin A termed progerin. Progerin expression alters the organization of the nuclear lamina and chromatin. The life expectancy of HGPS patients is severely reduced due to critical cardiovascular defects. Progerin also accumulates in an age-dependent manner in the vascular cells of adults that do not carry genetic mutations associated with HGPS. The molecular mechanisms that lead to vascular dysfunction in HGPS may therefore also play a role in vascular aging. The vascular phenotypic and molecular changes observed in HGPS are strikingly similar to those seen with age, including increased senescence, altered mechanotransduction and stem cell exhaustion. This article discusses the similarities and differences between age-dependent and HGPS-related vascular aging to highlight the relevance of HGPS as a model for vascular aging. Induced pluripotent stem cells derived from HGPS patients are suggested as an attractive model to study vascular aging in order to develop novel approaches to treat cardiovascular disease.

  9. Insulin resistance in women with hirsutism

    OpenAIRE

    Cebeci, Filiz; Onsun, Nahide; Mert, Meral

    2012-01-01

    Introduction There are still not enough data showing whether patients with idiopathic hirsutism (IH) also have insulin resistance. The association between polycystic ovary syndrome (PCOS) and insulin resistance is well documented in the literature, but the Rotterdam Consensus has concluded that principally obese women with PCOS should be screened for the metabolic syndrome. We intended to investigate the presence/absence of insulin resistance in non-obese women with hirsutism. Material and me...

  10. Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity

    OpenAIRE

    Rodriguez Susana; Teran Carlos G; Caceres Margoth; Medina Marcos

    2008-01-01

    Abstract Background Obesity is a one of the most common nutritional disorder worldwide, clearly associated with the metabolic syndrome, condition with implications for the development of many chronic diseases. In the poorest countries of Latin America, malnourishment is still the most prevalent nutritional problem, but obesity is emerging in alarming rates over the last 10 years without a predictable association with metabolic syndrome. The objective of our study was to determine the associat...

  11. Effect of Continuous Positive Airway Pressure Therapy on Glycemic Excursions and Insulin Sensitivity in Patients with Obstructive Sleep Apnea-hypopnea Syndrome and Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Guo; Xin Zhao; Qi Pan; Xue Sun; Hui Li; Xiao-Xia Wang; Li-Na Zhang

    2015-01-01

    Background:For patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and type 2 diabetes mellitus (T2DM),the night sleep interruption and intermittent hypoxia due to apnea or hypopnea may induce glycemic excursions and reduce insulin sensitivity.This study aimed to investigate the effect of continuous positive airway pressure (CPAP) therapy in patients with OSAHS and T2DM.Methods:Continuous glucose monitoring system (CGMS) was used in 40 patients with T2DM and newly diagnosed OSAHS.The measurements were repeated after 30 days of CPAP treatment.Subsequently,insulin sensitivity and glycohemoglobin (HbA1c) were measured and compared to the pretreatment data.Results:After CPAP therapy,the CGMS indicators showed that the 24-h mean blood glucose (MBG) and the night time MBG were significantly reduced (P < 0.05 and P =0.03,respectively).The mean ambulatory glucose excursions (MAGEs) and the mean of daily differences were also significantly reduced (P < 0.05 and P =0.002,respectively) compared to pretreatment levels.During the night,MAGE also significantly decreased (P =0.049).The differences between the highest and lowest levels of blood glucose over 24 h and during the night were significantly lower than prior to CPAP treatment (P < 0.05 and P =0.024,respectively).The 24 h and night time durations of high blood glucose (>7.8 mmol/L and > 11.1 mmol/L) decreased (P < 0.05 and P < 0.05,respectively) after the treatment.Inaddition,HbA1c levels were also lower than those before treatment (P < 0.05),and the homeostasis model assessment index of insulin resistance was also significantly lower than before CPAP treatment (P =0.034).Conclusions:CPAP therapy may have a beneficial effect on improving not only blood glucose but also upon insulin sensitivity in T2DM patients with OSAHS.This suggests that CPAP may be an effective treatment for T2DM in addition to intensive diabetes management.

  12. Clinical analysis of the insulin resistance and metabolic syndrome on first-epside schizophrenia patients%首发精神分裂症伴发胰岛素抵抗的临床分析

    Institute of Scientific and Technical Information of China (English)

    朱海兵; 李洁; 邱畅; 黄杏梅; 党亚梅; 刘学军; 王丹逢; 林育华

    2008-01-01

    Objective The aim of this sdudy was to analyse the metabolic abnormalities in first epirode, drug-free schizophrenia, and discuss the pathophysiologic mechanisms. Methods 120 patients with the first-epizode and drug-free schizophrenics, who met CCMD-3 and excluded hypertension and diabetes, were measured the BMI, waistline, the fasting blood glucoses (FBG) and insulin concentration (FIC), the cholesterol and TG before treatment. Subjects were assessed for the presence of insulin resistance using homeostasis model assessment(HOMA) and metabolic syndrome according to the criteria by the International Diabetes Federation (IDF),and we rated the positive and negative symptoms scales (PANSS). Results Metabolic abnormalities were already present in first-epizode patients ,28. 3% with centricity fatness, 20% with the lower FIC, 35% with insulin resistance, and 10. 83% achieving the criteria of metabolic syndrome, and much higher rates of metabolic abnormalities were observed in the older and female subjects. In patients, there were significantly correlations between waistline and body mass index (BMI) (n=120, r=0.758,P<0.01). They were also positively related to the age, weight, the FBG ,TG and cholesterol concentration, but had no relationship to the durations and FIC. The index of insulin resistance was positively related to waistline (r=0.207, P<0.05) and the fasting insulin concentration. The metabolic indexes were negatively related to the P, N, G and the totoal scores of PANSS(P> 0.05). Conclusion The current data suggested that the high incidence of the insulin resistance and metabolic syndrome be a major problem for the first-epside schizophrenia patients. We should build the early interference models for metabolic abnormalities including the centricity fatness, the insulin resistance and lipid abnormalities in first-epside schizophrenia patients.%目的 分析首发未用药的精神分裂症患者伴发代谢紊乱的临床状况,并探

  13. 多囊卵巢综合征患者高雄激素的相关性研究%Correlation of hyperandrogenism with insulin resistance and serum luteinizing hormone in the patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    熊冬梅; 谷霞; 许良智; 李蓉

    2013-01-01

    Objective The aim of this study was to explore the relationship and significance of hyperandrogenism with insulin resistance and serum luteinizing hormone in patients with polycystic ovary syndrome (PCOS).Methods One hundred patients with PCOS were classified as HI-PCOS(n =50)or non-HI-PCOS (n =50)based on the present or absent of HI (fasting insulin level > 15mIU/L),age-and body index-matched.Crinosity score and serum levels of gonadotropins,ovarian steroids,glucose and insulin were determined.Insulin resistance index (HOMA-IR) was calculated.The association of serum androgen levels with HOMA-IR and LH/FSH were analyzed in the two groups,respectively.Results The Crinosity score and serum testosterone were positively correlated with LH/FSH and HOMA-IR in the HI-PCOS group.Crinosity score and serum testosterone was positively correlated with LH/FSH but not correlated with HOMA-IR in the non-HI-PCOS group.There was no correlation between LH/FSH and HOMA-IR in either HI-PCOS group or non-HI-PCOS group.Conclusion Hyperandrogenism is associated with both hyperinsulinemia and raised LH level in PCOS patients.Since there is no correlation between LH/FSH and HOMA-IR suggesting that hyperinsulinemia and LH are perhaps taking effect independently in PCOS patient.%目的 研究多囊卵巢综合征(Polycystic ovary syndrome,PCOS)患者高雄激素临床表现及其与胰岛素抵抗(IR)、高黄体生成素(LH)血症的相关关系及其意义.方法 100例PCOS患者以空腹胰岛素水平≥15 mIU/L为高胰岛素血症(hyperinsulinemia,HI)标准,按年龄、体重指数配对原则将其分为HI-PCOS组和non-HI-PCOS组各50例,分别进行多毛评分并测定卵泡早期血清性激素水平、空腹葡萄糖及胰岛素水平,计算胰岛素抵抗指数(HOMA-IR),对2组患者血生化参数进行比较并进行相关性分析.结果 HI-PCOS组患者多毛评分与血清T水平与LH/FSH及HOMA-IR呈正相关(r=0.925,r=0.731,r=0.721,P<0.05);non-HI-PCOS组患者多

  14. 多囊卵巢综合征血脂代谢与胰岛素抵抗的关系探讨%Cystic ovarian syndrome to explore the relationship between blood lipid metabolism and insulin resistance

    Institute of Scientific and Technical Information of China (English)

    刘舒婷; 张莹

    2016-01-01

    Objective: To investigate the relationship between lipid metabolism and insulin resistance in patients with polycystic ovary syndrome. Methods: January 2012 ~ December 2012 in our hospital for treatment of polycystic ovary syndrome in 60 patients for the study, a retrospective analysis of clinical data for all patients, compare observed in patients with dyslipidemia and insulin resistance relationship. Results: polycystic ovary syndrome Insulin resistance was 75.00%, compared with patients with non-insulin resistance, with significant differences; the overall lipid metabolism in patients with polycystic ovary syndrome abnormal incidence of 83.33%, resistance group was 25.00% abnormal blood lipids, lipid metabolism abnormality non-insulin resistant group was 58.33%, with a significant difference between the two groups, P<0.05, with statistical significance. Conclusions: In clinical treatment, the incidence of polycystic ovary syndrome lipid metabolism and insulin resistance in patients with generally higher, abnormal lipid metabolism and insulin resistance is proportional.%目的:探讨多囊卵巢综合征患者的血脂代谢与胰岛素抵抗的关系。方法:选取2012年1~12月在我院进行多囊卵巢综合征治疗的60例患者作为研究对象,回顾性分析所有患者的临床资料,观察患者的血脂异常与胰岛素抵抗的关系。结果:多囊卵巢综合征患者胰岛素抵抗的发生率为75.00%,与非胰岛素抵抗的患者相比,具有明显差异;多囊卵巢综合征患者总体血脂代谢异常的发生率为83.33%,抵抗组血脂异常发生率为25.00%,非胰岛素抵抗组为58.33%,组间具有明显差异,P<0.05,具有统计学意义。结论:在临床治疗中,多囊卵巢综合征患者的血脂代谢与胰岛素抵抗的发生率一般较高,血脂代谢异常与胰岛素抵抗呈