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Sample records for early diabetic cardiomyopathy

  1. Early molecular events in the development of the diabetic cardiomyopathy.

    NARCIS (Netherlands)

    Monkemann, H.; Vriese, A.S. de; Blom, H.J.; Kluijtmans, L.A.J.; Heil, S.G.; Schild, H.H.; Golubnitschaja, O.

    2002-01-01

    Oxidative damage to DNA has been well documented in cardiac cells isolated from diabetic patients and rats with streptozotocin-induced diabetes mellitus (DM). This study evaluates possible molecular mechanisms for early events in the development of DM-induced cardiomyopathy. Methods: To analyze the

  2. Diabetic Cardiomyopathy: Bench to Bedside

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    Schilling, Joel D.; Mann, Douglas L.

    2012-01-01

    The study of diabetic cardiomyopathy (diabetic CM) is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic CM with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. PMID:22999244

  3. Type I Diabetic Akita Mouse Model is Characterized by Abnormal Cardiac Deformation During Early Stages of Diabetic Cardiomyopathy with Speckle-Tracking Based Strain Imaging.

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    Zhou, Yingchao; Xiao, Hong; Wu, Jianfei; Zha, Lingfeng; Zhou, Mengchen; Li, Qianqian; Wang, Mengru; Shi, Shumei; Li, Yanze; Lyu, Liangkun; Wang, Qing; Tu, Xin; Lu, Qiulun

    2018-01-01

    Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

  4. Mitochondrial Dynamics in Diabetic Cardiomyopathy

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    Galloway, Chad A.

    2015-01-01

    Abstract Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545–1562. PMID

  5. Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy.

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    Sebastián D Calligaris

    Full Text Available BACKGROUND/AIM: Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. METHODS/RESULTS: Male C57BL/6 mice were fed with a standardized high-fat diet (obese or regular diet (normal for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method and by hemodynamic parameters (invasive method. Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction, and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. CONCLUSIONS: Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.

  6. Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus

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    Langhorn, R.; Kieler, I. N.; Koch, J.

    2018-01-01

    Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independe......Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM......), independently of CKD, are associated with changes in serum SDMA. Animals: Ninety-four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls). Methods: Case-control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed....... Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log-transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA. Results: Median (range) serum...

  7. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

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    ... in childhood, people with EOMFC may also develop joint deformities called contractures that restrict the movement of ... Home Edition for Patients and Caregivers: Dilated Cardiomyopathy Neuromuscular Disease Center, Washington University Orphanet: Early-onset myopathy ...

  8. Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

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    Xue Zhao

    2011-09-01

    Full Text Available Heart failure (HF is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN and flavin adenine dinucleotide (FAD, enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ (70 mg /kg. Riboflavin (20 mg/kg was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD, the level of malondialdehyde (MDA as well as heme oxygenase-1 (HO-1 protein level. Myocardial connective tissue growth factor (CTGF level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP rate of pressure rose (+dp/dt, and rate of pressure decay (−dp/dt were depressed while left ventricular enddiastolic pressure (LVEDP was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest

  9. Norepinephrine storage, distribution, and release in diabetic cardiomyopathy

    International Nuclear Information System (INIS)

    Ganguly, P.K.; Beamish, R.E.; Dhalla, K.S.; Innes, J.R.; Dhalla, N.S.

    1987-01-01

    The ability of hearts to store, distribute, and release norepinephrine (NE) was investigated in rats 8 wk after the induction of diabetes by an injection of streptozotocin. Chronic diabetes was associated with increased content and concentration of NE in heart and in other tissues such as kidney, brain, and spleen. Reserpine or tyramine treatment resulted in depletion of endogenous cardiac NE in control and diabetic rats. The depletion of NE stores at different times after a dose of reserpine was greater in diabetic hearts. On the other hand, NE stores in diabetic hearts were less sensitive than control hearts to low doses of tyramine but were more sensitive to high doses. The uptake of [ 3 H]NE was greater in diabetic hearts in isolated perfused preparations. In comparison with the control values, diabetic hearts showed a decrease in [ 3 H]NE in the granular fraction and an increase in the supernatant fraction. Diabetic hearts also showed an accelerated spontaneous release of [ 3 H]NE. The increased cardiac NE and the uptake and release of NE in diabetic animals were reversible upon treatment with insulin. These results are consistent with the view that sympathetic activity is increased in diabetic cardiomyopathy and indicate that cardiac NE in diabetic rats is maintained at a higher level partly due to an increased uptake of released NE by adrenergic nerve terminals

  10. Frequency of diabetic cardiomyopathy among type-2 diabetics presenting as heart failure

    International Nuclear Information System (INIS)

    Muhammad, Z.; Hashmi, A.

    2013-01-01

    To determine the frequency of diabetic cardiomyopathy among patients with type-2 diabetes presenting with overt heart failure. Study Design: Case series. Place and Duration of Study: Department of Cardiology, Mayo Hospital, Lahore, from April 2008 to July 2009. Methodology: One hundred patients with type-2 diabetes mellitus having symptoms and signs of heart failure were enrolled. Anthropometric parameters were recorded and all patients had investigations including complete blood count, blood glucose (fasting and random), serum creatinine, fasting lipid profile, haemoglobin A1c, chest X-ray, electrocardiogram and Doppler echocardiography. After stabilization, every patient underwent coronary angiography. The data was entered in a structured proforma. Results: Sixty (60%) patients were males and 40 (40%) were females. Duration of diabetes was > 10 years in all. Eighty (80%) were on oral hypoglycemic and 20 (20%) were on insulin. Diabetic cardiomyopathy was found in 40 patients (40%) of the total study patients. Forty percent (40%) patients had marked left ventricular (LV) systolic dysfunction (ejection fraction < 30%). Three (5%) patients died during hospitalization. Conclusion: Diabetic cardiomyopathy is a fairly common cause of heart failure in the native population with type-2 diabetes mellitus and results in high morbidity and mortality. (author)

  11. Cardiomyopathy

    Science.gov (United States)

    ... as a disorder that causes the buildup of abnormal proteins (amyloidosis), a disease that causes inflammation and can cause lumps of ... Cardiomyopathy can lead to abnormal heart rhythms. These abnormal heart rhythms ... other types of heart disease by living a heart-healthy lifestyle and making ...

  12. Subtle abnormalities in contractile function are an early manifestation of sarcomere mutations in dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Lakdawala, Neal K; Thune, Jens J; Colan, Steven D

    2012-01-01

    Sarcomere mutations cause both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM); however, the steps leading from mutation to disease are not well described. By studying mutation carriers before a clinical diagnosis develops, we characterize the early manifestations of sarcomere...... mutations in DCM and investigate how these manifestations differ from sarcomere mutations associated with HCM....

  13. MECHANISMS IN ENDOCRINOLOGY: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review.

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    Levelt, Eylem; Gulsin, Gaurav; Neubauer, Stefan; McCann, Gerry P

    2018-04-01

    Heart failure is a major cause of morbidity and mortality in type 2 diabetes. Type 2 diabetes contributes to the development of heart failure through a variety of mechanisms, including disease-specific myocardial structural, functional and metabolic changes. This review will focus on the contemporary contributions of state of the art non-invasive technologies to our understanding of diabetic cardiomyopathy, including data on cardiac disease phenotype, cardiac energy metabolism and energetic deficiency, ectopic and visceral adiposity, diabetic liver disease, metabolic modulation strategies and cardiovascular outcomes with new classes of glucose-lowering therapies. © 2018 The authors.

  14. Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.

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    Lai, Jinsheng; Chen, Fuqiong; Chen, Jing; Ruan, Guoran; He, Mengying; Chen, Chen; Tang, Jiarong; Wang, Dao Wen

    2017-03-14

    Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.

  15. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

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    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

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    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  17. Preservation of the positive lusitropic effect of beta-adrenoceptors stimulation in diabetic cardiomyopathy.

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    Amour, Julien; Loyer, Xavier; Michelet, Pierre; Birenbaum, Aurélie; Riou, Bruno; Heymes, Christophe

    2008-10-01

    In diabetic cardiomyopathy, diastolic dysfunction results in part from sarcoplasmic reticulum abnormalities affecting both phospholamban and sarcoplasmic reticulum Ca2+ uptake (SERCA2a). Consequently, the positive lusitropic effect of beta-adrenoceptors stimulation could be altered, and beta3-adrenoceptor over-expression may play a role, as previously demonstrated with an altered positive inotropic effect. In this study, we tested the hypothesis that the beta-adrenergic positive lusitropic effect is altered in diabetic cardiomyopathy, and that beta3-adrenoceptor over-expression is involved. beta-adrenergic responses were investigated in vivo (dobutamine-echocardiography) and in vitro (papillary muscle preparation) in healthy and diabetic rats killed 4 (4W) and 12 (12W) wk after IV streptozotocin injection. The effect of beta3-adrenoceptor pathway inhibition by S-cyanopindolol (selective beta3-adrenoceptor antagonist) or by NG-nitro-L-arginine-methyl-ester (nonselective nitric oxide synthase inhibitor) on the lusitropic response to isoproterenol (nonselective beta-adrenoceptors agonist) was studied in vitro. Western blots were performed to quantify the protein expressions of beta1- and beta3-adrenoceptors, phospholamban, and SERCA2a. Data are presented as mean percentages of baseline+/-sd. Despite the increased phospholamban/SERCA2a protein ratio and documented diastolic dysfunction, the positive lusitropic effect of beta-adrenoceptors stimulation was preserved in vivo (dobutamine) and in vitro (isoproterenol) in 4W and 12W diabetic, compared with healthy, rats. The beta3-adrenoceptor was up-regulated whereas beta1-adrenoceptor was down-regulated in 4W and 12W diabetic, compared with healthy, rats. Nevertheless, S-cyanopindolol or NG-nitro-L-arginine-methyl-ester had no lusitropic effect. The positive lusitropic effect of beta-adrenoceptor stimulation was preserved in diabetic cardiomyopathy. beta3-adrenoceptor over-expression does not seem to affect this process.

  18. Noninvasive assessment of cardiomyopathy in normotensive diabetic patients between 20 and 50 years old

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    Bouchard, A.; Sanz, N.; Botvinick, E.H.; Phillips, N.; Heilbron, D.; Byrd, B.F. III; Karam, J.H.; Schiller, N.B.

    1989-01-01

    To further the understanding of diabetic heart disease, we tested the hypothesis that an asymptomatic group of normotensive diabetic patients between 20 and 50 years old had a restrictive cardiomyopathy independent of clinically significant coronary artery disease. Quantitative two-dimensional echocardiography and stress myocardial perfusion scintigraphy were performed to detect and characterize the cardiac abnormalities in this study group comprising 88 patients with rigorously classified diabetes and 65 volunteer control subjects. Diabetic patients were shown to have a mildly reduced left ventricular end-diastolic volume index: 50.1 +/- 8.2 and 52.1 +/- 14.7 mL/m2 for patients with type I and type II diabetes, respectively, versus 58.9 +/- 11.7 mL/m2 for control subjects. The left ventricular diastolic filling was also impaired in diabetic patients as reflected by a lower atrial emptying index: 0.73 +/- 0.24 and 0.76 +/- 0.3 for type I and type II diabetics, respectively, compared with 1.14 +/- 0.24 for control subjects. Exercise tolerance was normal in subjects with type I diabetes and slightly reduced in subjects with type II diabetes. Only one patient developed regional ischemia on thallium exercise testing. Using a comprehensive, noninvasive approach, we have shown that asymptomatic normotensive patients with type I or type II diabetes who were between 20 and 50 years old had a restrictive cardiomyopathy characterized by mildly reduced left ventricular end-diastolic volume and altered left ventricular compliance independent of critical coronary artery disease

  19. Cardiomyopathy in neurological disorders.

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    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. My Sweetheart Is Broken: Role of Glucose in Diabetic Cardiomyopathy

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    Manoja K. Brahma

    2017-01-01

    Full Text Available Despite overall reductions in heart disease prevalence, the risk of developing heart failure has remained 2-fold greater among people with diabetes. Growing evidence has supported that fluctuations in glucose level and uptake contribute to cardiovascular disease (CVD by modifying proteins, DNA, and gene expression. In the case of glucose, clinical studies have shown that increased dietary sugars for healthy individuals or poor glycemic control in diabetic patients further increased CVD risk. Furthermore, even after decades of maintaining tight glycemic control, susceptibility to disease progression can persist following a period of poor glycemic control through a process termed "glycemic memory." In response to chronically elevated glucose levels, a number of studies have identified molecular targets of the glucose-mediated protein posttranslational modification by the addition of an O-linked N-acetylglucosamine to impair contractility, calcium sensitivity, and mitochondrial protein function. Additionally, elevated glucose contributes to dysfunction in coupling glycolysis to glucose oxidation, pentose phosphate pathway, and polyol pathway. Therefore, in the "sweetened" environment associated with hyperglycemia, there are a number of pathways contributing to increased susceptibly to "breaking" the heart of diabetics. In this review we will discuss the unique contribution of glucose to heart disease and recent advances in defining mechanisms of action.

  1. Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up‐regulation contribute to the onset of diabetic cardiomyopathy

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    Ma, Heng; Li, Shi‐Yan; Xu, Peisheng; Babcock, Sara A.; Dolence, E. Kurt; Brownlee, Michael; Li, Ji

    2008-01-01

    Abstract Diabetic cardiomyopathy is manifested by compromised systolic and diastolic function. This study was designed to examine the role of advanced glycation endproduct (AGE) and AGE receptor (RAGE) in diabetic cardiomyopathy. Heart function was assessed in isolated control and streptozotocin‐induced diabetic hearts following in vivo RAGE gene knockdown using RNA interference. Cardiomyocyte mechanical properties were evaluated including peak shortening (PS), time‐to‐PS (TPS) and time‐to‐90% relengthening (TR90). RAGE was assayed by RT‐PCR and immunoblot. Diabetes significantly enhanced cardiac MG, AGE and RAGE levels accompanied with colocalization of AGE and RAGE in cardiomyocytes. Diabetes‐elicited increase in RAGE was inhibited by in vivo siRNA interference. The AGE formation inhibitor benfotiamine significantly attenuated diabetes‐induced elevation in MG, AGE, RAGE and collagen cross‐linking without affecting hypertriglyceridaemia and hypercholesterolaemia in diabetes. Diabetes markedly decreased LV contractility, as evidenced by reduced ±dP/dt and LV developed pressure (LVDP), which were protected by RAGE gene knockdown. In addition, MG‐derived AGE (MG‐AGE) up‐regulated cardiac RAGE mRNA and triggered cardiomyocyte contractile dysfunction reminiscent of diabetic cardiomyopathy. The MG‐AGE‐elicited prolongation of TPS and TR90 was ablated by an anti‐RAGE antibody in cardiomyocytes. Interestingly, MG‐AGE‐induced cardiomyocyte dysfunction was associated with mitochondrial membrane potential (MMP) depolarization and reduced GSK‐3β inactivation in control cardiomyocytes, similar to those from in vivo diabetes. Treatment with siRNA‐RAGE ablated diabetes‐induced MMP depolarization and GSK‐3β inactivation. Collectively, our result implicated a role of AGE‐RAGE in the pathogenesis of diabetic cardiomyopathy. PMID:19602045

  2. The Chinese Herb Yi-Qi-Huo-Xue Protects Cardiomyocyte Function in Diabetic Cardiomyopathy

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    Xiangsheng Wang

    2018-01-01

    Full Text Available Aims. To study the effect of the Chinese herb Yi-qi-huo-xue on cardiomyopathy in diabetic rats. Methods. Rats were fed a high fat and high glucose diet and injected with 50 ml/kg streptozotocin (STZ to induce diabetic cardiomyopathy (DCM, followed by treatment with Yi-qi-huo-xue for 4 weeks. We measured the rats’ heart weight index, observed the myocardial morphology using hematoxylin eosin (HE staining, and determined the content of collagen types I and III in the myocardium using enzyme-linked immunosorbent assay (ELISA. We determined Bcl-2, Bax, and P53 protein expression by Western blot analysis and the cardiomyocyte apoptosis rate via a flow cytometry assay. Results. Compared with the rats in the control group, the diabetic rats gained weight and had increased blood sugar levels, an enhanced heart weight index, and increased myocardial pathophysiological damage. There was a decrease in their Bcl-2 expression, and their Bax and P53 expression increased. The Bcl-2/Bax ratio was enhanced, and there was an increase in the content of collagen types I and III in the myocardium. After treatment with Yi-qi-huo-xue, all levels listed above returned to normal. Conclusion. The Chinese herb Yi-qi-huo-xue degraded the myocardial interstitial collagen types I and III to protect the myocardium of the diabetic rats, thus delaying the role of myocardial fibrosis. Yi-qi-huo-xue could play an important role in protecting the myocardium of DCM rats by enhancing the expression of the Bcl-2 protein, inhibiting the expression of the Bax and P53 proteins, increasing the ratio of Bcl-2/Bax, and inhibiting the apoptosis of cardiomyocytes.

  3. Early onset type 2 diabetes

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    Bo, A; Thomsen, R W; Nielsen, J S

    2018-01-01

    was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age-gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2......AIM: To examine the association between early onset of type 2 diabetes (DM) and clinical and behavioural risk factors for later diabetes complications. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic...... Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early-onset) with diagnosis age 46-55, 56-65 (average-onset = reference), 66-75, and >75 years (late-onset). Prevalence ratios (PRs) were computed using Poisson regression. RESULTS: Poor...

  4. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

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    Aude Carillion

    Full Text Available In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes.β-adrenergic responses were investigated in vivo (echocardiography and ex vivo (left ventricular papillary muscles in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1. Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD.Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4. Nitric oxide synthase (NOS inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response.Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  5. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.

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    Carillion, Aude; Feldman, Sarah; Na, Na; Biais, Matthieu; Carpentier, Wassila; Birenbaum, Aurélie; Cagnard, Nicolas; Loyer, Xavier; Bonnefont-Rousselot, Dominique; Hatem, Stéphane; Riou, Bruno; Amour, Julien

    2017-01-01

    In the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their "pleiotropic" effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes. β-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD. Atorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response. Atorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

  6. Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

    Science.gov (United States)

    Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Giridharan, Vijayasree V; Sreedhar, Remya; Bose, Rajendran J C; Vanama, Jyothi; Palaniyandi, Suresh S; Konishi, Tetsuya; Watanabe, Kenichi; Thandavarayan, Rajarajan A

    2017-02-01

    Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. A Comparative Summary on Antioxidant-like Actions of Timolol with Other Antioxidants in Diabetic Cardiomyopathy.

    Science.gov (United States)

    Turan, Belma

    2016-01-01

    Cellular signaling associated with cardiac β-adrenergic receptors (β-AR) is composed of coupled mechanism among β 1-/β2-AR and Gs proteins with contribution of constitutive β3-AR coupling to Gi proteins. However, down-regulation of β-ARs in the heart under pathological conditions is mediated with a signaling G proteins-included mechanism. Additionally, there are serious conflicting data on this field in literature yet. Although some of these conflictions are generally related with either experimental protocols for different approaches or different animal models. To treat cardiovascular disorders, generally, various types of β-blockers are used while their action mechanisms are not fully known yet. Furthermore, although β-blockers are generally used to block the activated β-ARs, they can be used to scavenge free radicals under oxidative stress. Studies, in whole-system, organ or cellular levels, showed that some β-blockers, including timolol, have protective-actions against increased oxidative stress in diseased heart via ROSscavenging. Additionally, it has been mentioned that some β-blockers nicely prevented the development of heart failure in both experimental and clinical studies by restoring sarcoplasmic reticulum (SR) Ca(2+) release channels, RyR2. Since diabetic cardiomyopathy is recognized due to its diminished responsiveness to β1-AR agonist stimulation in the heart with an up-regulation of β 3-AR, inducing a strong negative inotropic effect on left ventricular function, it has been shown that treatment of streptozotocin-diabetic rats with timolol provided a marked cardio-protection. Importantly, it has been also documented that timolol treatment-dependent cardio-protection in diabetic rats includes basically prevention of RyR2- hyperphosphorylation, which, in turn, block Ca(2+)-leakage from SR via scavenging oxidative agents to control redox-state of cardiomyocytes. This action of timolol in diabetic heart is very similar to other known

  8. The critical role of Astragalus polysaccharides for the improvement of PPARα [ correction of PPRAα]-mediated lipotoxicity in diabetic cardiomyopathy.

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    Wei Chen

    Full Text Available BACKGROUND: Obesity-related diabetes mellitus leads to increased myocardial uptake and oxidation of fatty acids, resulting in a form of cardiac dysfunction referred to as lipotoxic cardiomyopathy. We have shown previously that Astragalus polysaccharides (APS administration was sufficient to improve the systemic metabolic disorder and cardiac dysfunction in diabetic models. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the precise role of APS therapy in the pathogenesis of myocardial lipotoxity in diabetes, db/db diabetic mice and myosin heavy chain (MHC- peroxisome proliferator-activated receptor (PPAR α mice were characterized and administrated with or without APS with C57 wide- type mice as normal control. APS treatment strikingly improved the myocyte triacylglyceride accumulation and cardiac dysfunction in both db/db mice and MHC-PPARα mice, with the normalization of energy metabolic derangements in both db/db diabetic hearts and MHC-PPARα hearts. Consistently, the activation of PPARα target genes involved in myocardial fatty acid uptake and oxidation in both db/db diabetic hearts and MHC-PPARα hearts was reciprocally repressed by APS administration, while PPARα-mediated suppression of genes involved in glucose utilization of both diabetic hearts and MHC-PPARα hearts was reversed by treatment with APS. CONCLUSIONS: We conclude that APS therapy could prevent the development of diabetic cardiomyopathy through a mechanism mainly dependent on the cardiac PPARα-mediated regulatory pathways.

  9. Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates Type 2 Diabetes and Its Associated Cardiomyopathy.

    Science.gov (United States)

    Bhattacharjee, Niloy; Khanra, Ritu; Dua, Tarun K; Das, Susmita; De, Bratati; Zia-Ul-Haq, M; De Feo, Vincenzo; Dewanjee, Saikat

    2016-01-01

    Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. SR was chemically characterized by GC-MS analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg, intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level was measured at specific intermissions. Serum biochemical and inflammatory markers were estimated after sacrificing the animals. Besides, myocardial redox status, expressions of signal proteins (NF-κB and PKCs), histological and ultrastructural studies of heart were performed in the controls and SR treated T2D rats. Phytochemical screening of the crude extract revealed the presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated fatty acids within SR. T2D rats exhibited significantly (p disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological and ultra-structural studies of cardiac tissues supported the protective characteristics of SR. From the present findings it can be concluded that, SR could offer protection against T2DM and its associated cardio-toxicity via multiple mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.

  10. A case of Becker muscular dystrophy with early manifestation of cardiomyopathy

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    Ki Hyun Doo

    2012-09-01

    Full Text Available An 18-year-old boy was admitted with chest discomfort, nausea, and dyspnea at rest. At the age of 3 years, he underwent muscle biopsy and dystrophin gene analysis owing to an enlarged calf muscle and elevated serum kinase level (6,378 U/L without overt weakness; based on the results, Becker muscular dystrophy (BMD was diagnosed. The dystrophin gene showed deletion of exons 45 to 49. He remained ambulant and could step upstairs without significant difficulties. A chest roentgenogram showed cardiomegaly (cardiothoracic ratio, 54%, and his electrocardiogram (ECG showed abnormal ST-T wave, biatrial enlargement, and left ventricular hypertrophy. The 2-dimensional and M-mode ECGs showed a severely dilated left ventricular cavity with diffuse hypokinesis. The systolic indices were reduced, including fractional shortening (9% and ejection fraction (19%. Despite receiving intensive medical treatment, he died from congestive heart failure 5 months after the initial cardiac symptoms. We report a case of BMD with early-onset dilated cardiomyopathy associated with deletion of exons 45 to 49. Early cardiomyopathy can occur in BMD patients with certain genotypes; therefore, careful follow-up is required even in patients with mild phenotypes of BMD.

  11. Towards Early Detection and Risk Stratification of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

    NARCIS (Netherlands)

    Riele, A.S.J.M. te

    2016-01-01

    Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by frequent ventricular arrhythmias and usually slowly progressive ventricular dysfunction. Since its initial description in 1982, sudden cardiac death (SCD) occurring in young and usually

  12. Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice

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    Shudong Wang

    2017-03-01

    Full Text Available Diabetic cardiomyopathy (DCM is highly prevalent in type 2 diabetes (T2DM patients. Zinc is an important essential trace metal, whose deficiency is associated with various chronic ailments, including vascular diseases. We assessed T2DM B6.BKS(D-Leprdb/J (db/db mice fed for six months on a normal diet containing three zinc levels (deficient, adequate, and supplemented, to explore the role of zinc in DCM development and progression. Cardiac function, reflected by ejection fraction, was significantly decreased, along with increased left ventricle mass and heart weight to tibial length ratio, in db/db mice. As a molecular cardiac hypertrophy marker, atrial natriuretic peptide levels were also significantly increased. Cardiac dysfunction and hypertrophy were accompanied by significantly increased fibrotic (elevated collagen accumulation as well as transforming growth factor β and connective tissue growth factor levels and inflammatory (enhanced expression of tumor necrosis factor alpha, interleukin-1β, caspase recruitment domain family member 9, and B-cell lymphoma/leukemia 10, and activated p38 mitogen-activated protein kinase responses in the heart. All these diabetic effects were exacerbated by zinc deficiency, and not affected by zinc supplementation, respectively. Mechanistically, oxidative stress and damage, mirrored by the accumulation of 3-nitrotyrosine and 4-hydroxy-2-nonenal, was significantly increased along with significantly decreased expression of Nrf2 and its downstream antioxidants (NQO-1 and catalase. This was also exacerbated by zinc deficiency in the db/db mouse heart. These results suggested that zinc deficiency promotes the development and progression of DCM in T2DM db/db mice. The exacerbated effects by zinc deficiency on the heart of db/db mice may be related to further suppression of Nrf2 expression and function.

  13. Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice.

    Science.gov (United States)

    Zhang, Zhihao; Zhang, Duoduo; Dou, Mengmeng; Li, Zhubo; Zhang, Jie; Zhao, Xiaoyan

    2016-12-01

    Dendrobium officinale Kimura et Migo (Dendrobium catenatum Lindley), a prized traditional Chinese Medicine, has been used in China and Southeast Asian countries for centuries. The present study was aimed to investigate the effects and the possible mechanisms of the Dendrobium officinale extracts (DOE) on diabetic cardiomyopathy in mice. The diabetic model was induced by intraperitoneal injection of streptozotocin at the dose of 50mg/kg body weight for 5 consecutive days. After 8 weeks treatment of DOE, mice were sacrificed, blood sample and heart tissues were collected. Our results showed that Streptozotocin-induced diabetic model was effectively achieved and serum CK and LDH levels were significantly increased in mice with diabetic cardiomyopathy. Pretreatment with DOE decreased the heart-to-body weight ratio (HW/BW) and showed an evident hypoglycemic effect. DOE pretreatment significantly decreased CK, LDH, TC and TG levels, limited the production of MDA and increased the activities of T-SOD. The histological analysis of Oil red O staining and Sirius red staining showed an obvious amelioration of cardiac injury, inhibition of cardiac lipid accumulation and deposition of collagen when pretreatment with DOE. In addition, Western blot detection and analysis showed that DOE down-regulated the expression of TGF-β, collegan-1, fibronectin, NF-κB, TNF-α and IL-1β. In conclusion, our study suggested that DOE possesses the cardioprotective potential against diabetic cardiomyopathy, which may be due to the inhibition of oxidative stress, cardiac lipid accumulation, pro-inflammatory cytokines and cardiac fibrosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

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    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  15. The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy

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    Zheng Xu

    2016-12-01

    Full Text Available Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM. Although many studies have explored the mechanisms leading to DCM, the pathophysiology of DCM has not yet been fully clarified. In fact, as a potential mechanism, the associations between DCM development and mitogen-activated protein kinase (MAPK activation have been the subjects of tremendous interest. Nonetheless, much remains to be investigated, such as tissue- and cell-specific processes of selection of MAPK activation between pro-apoptotic vs. pro-survival fate, as well as their relation with the pathogenesis of diabetes and associated complications. In general, it turns out that MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2, c-Jun N-terminal protein kinase (JNK and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction, hypertrophy, fibrosis and heart failure. As one of MAPK family members, the activation of ERK1/2 has also been known to be involved in cardiac hypertrophy and dysfunction. However, many recent studies have demonstrated that ERK1/2 signaling activation also plays a crucial role in FGF21 signaling and exerts a protective environment of glucose and lipid metabolism, therefore preventing abnormal healing and cardiac dysfunction. The duration, extent, and subcellular compartment of ERK1

  16. What Is Cardiomyopathy?

    Science.gov (United States)

    ... underlying conditions, such as diabetes and high blood pressure . Cardiomyopathy often runs in families. Your doctor may suggest that your parents, brothers and sisters, and children get checked to see whether they have the ...

  17. Catalase inhibition in diabetic rats potentiates DNA damage and apoptotic cell death setting the stage for cardiomyopathy.

    Science.gov (United States)

    Ivanović-Matić, Svetlana; Bogojević, Desanka; Martinović, Vesna; Petrović, Anja; Jovanović-Stojanov, Sofija; Poznanović, Goran; Grigorov, Ilijana

    2014-12-01

    Diabetes is a risk factor for cardiovascular disease that has a multifactorial etiology, with oxidative stress as an important component. Our previous observation of a significant diabetes-related increase in rat cardiac catalase (CAT) activity suggested that CAT could play a major role in delaying the development of diabetic cardiomyopathy. Thus, in the present work, we examined the effects of the daily administration of the CAT inhibitor, 3-amino-1,2,4-triazole (1 mg/g), on the hearts of streptozotocin (STZ)-induced diabetic rats. Administration of CAT inhibitor was started from the 15th day after the last STZ treatment (40 mg/kg/5 days), and maintained until the end of the 4th or 6th weeks of diabetes. Compared to untreated diabetic rats, at the end of the observation period, CAT inhibition lowered the induced level of cardiac CAT activity to the basal level and decreased CAT protein expression, mediated through a decline in the nuclear factor erythroid-derived 2-like 2 /nuclear factor-kappa B p65 (Nrf2/NF-κB p65) subunit ratio. The perturbed antioxidant defenses resulting from CAT inhibition promoted increased H₂O₂production (P < 0.05) and lipid peroxidation (P < 0.05). Generated cytotoxic stimuli increased DNA damage (P < 0.05) and activated pro-apoptotic events, observed as a decrease (P < 0.05) in the ratio of the apoptosis regulator proteins Bcl-2/Bax, increased (P < 0.05) presence of the poly(ADP-ribose) polymerase-1 (PARP-1) 85 kDa apoptotic fragment and cytoplasmic levels of cytochrome C. These findings confirm an important function of CAT in the suppression of events leading to diabetes-promoted cardiac dysfunction and cardiomyopathy.

  18. In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of curcumin/PBLG-PEG-PBLG nanoparticles.

    Science.gov (United States)

    Tong, Fei; Chai, Rongkui; Jiang, Haiying; Dong, Bo

    2018-01-01

    The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H 2 S). Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks. The blood and myocardiums were collected, the level of serum H 2 S was observed, and the [Ca 2+ ] i content was measured in myocardial cells, and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected. Both curcumin and curcumin/P pretreatment alleviated pathological morphological damage of myocardium, increased H 2 S and [Ca 2+ ] i levels, and upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while curcumin/P remarkably augmented this effect. PBLG-PEG-PBLG could improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG significantly alleviated diabetic cardiomyopathy.

  19. Treadmill exercise alleviates diabetic cardiomyopathy by suppressing plasminogen activator inhibitor expression and enhancing eNOS in streptozotocin-induced male diabetic rats.

    Science.gov (United States)

    Chengji, Wang; Xianjin, Fan

    2018-04-01

    To investigate the biological mechanism of the effect of different intensity exercises on diabetic cardiomyopathy. 87 raise specific pathogen SPF healthy 6-week-old male Sprague-Dawley rats, fed 6 weeks with high-fat diet for rats were used, and a diabetic model was established by intraperitoneal injection of streptozotocin - randomly selected 43 rats were divided into Diabetic control group (DCG, n  = 10), Diabetic exercise group 1 (DEG1, n  = 11), Diabetic exercise group 2 (DEG2, n  = 11) and Diabetic exercise group 3 (DEG3, n  = 11). The rats in DEG1 were forced to run on a motorized treadmill, the exercise load consisted of running at a speed of 10 m/min, the exercise load of the rats in DEG2 were running at a speed of 15 m/min, the exercise load of the rats in DEG3 were running at a speed of 20 m/min, for one hour once a day for 6 weeks. After 6 weeks of exercise intervention, glucose metabolism-related indexes in rats such as blood glucose (FBG), glycosylated serum protein (GSP) and insulin (FINS); cardiac fibrinolytic system parameters such as PAI-1 (plasminogen activator inhibitor 1), Von Willebrand factor (vWF), protein kinase C (PKC) and diacylglycerol (DAG); and serum level of NO, eNOS and T-NOS were measured. Compared with DCG, fasting blood glucose and GSP were decreased, while insulin sensitivity index and insulin level were increased in all rats of the three exercise groups. FBG decrease was statistically significant ( P  diabetic rats; myocardial PAI-1 in DEG1, DEG2 and DEG3 rats decreased significantly ( P  diabetic cardiomyopathy by affecting the levels of PAI-1 and eNOS, and there is a dependence on intensity. © 2018 The authors.

  20. Early detection of diabetes after pregnancy complicated by gestational diabetes

    DEFF Research Database (Denmark)

    Nielsen, Jane Hyldgård; Overgaard, Charlotte; Olesen, Christinna Rebecca

    Title: Early detection of diabetes after pregnancy complicated by gestational diabetes Background: Women whose pregnancy was complicated by gestational diabetes have a 7-fold higher risk of developing diabetes, primarily type 2. 40% of women with a history gestational diabetes mellitus (GDM...... of health consequences for women. Aims: Examine the extent of participation in follow-up screening in the Danish Region of North Jutland, and the possible consequences of nonattendance. Methods: A register based study. In Danish national registers 2171 birthing women whose pregnancy was complicated by GDM...

  1. Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice.

    Science.gov (United States)

    Baumgardt, Shelley L; Paterson, Mark; Leucker, Thorsten M; Fang, Juan; Zhang, David X; Bosnjak, Zeljko J; Warltier, David C; Kersten, Judy R; Ge, Zhi-Dong

    2016-01-01

    Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known. The present study examined the effects of SEP and L-Cit on diabetic cardiomyopathy and ischemia/reperfusion injury in obese type 2 diabetic mice. Db/db and C57BLKS/J mice at 6 to 8 weeks of age received vehicle, SEP, or L-Cit orally alone or in combination for 8 weeks. Cardiac function was evaluated with echocardiography. Db/db mice displayed hyperglycemia, obesity, and normal blood pressure and cardiac function compared with C57BLKS/J mice at 6 to 8 weeks of age. After vehicle treatment for 8 weeks, db/db mice had reduced ejection fraction, mitral E/A ratio, endothelium-dependent relaxation of coronary arteries, tetrahydrobiopterin concentrations, ratio of endothelial nitric oxide synthase dimers/monomers, and nitric oxide levels compared with vehicle-treated C57BLKS/J mice. These detrimental effects of diabetes mellitus were abrogated by co-administration of SEP and L-Cit. Myocardial infarct size was increased, and coronary flow rate and ± dP/dt were decreased during reperfusion in vehicle-treated db/db mice subjected to ischemia/reperfusion injury compared with control mice. Co-administration of SEP and L-Cit decreased infarct size and improved coronary flow rate and cardiac function in both C57BLKS/J and db/db mice. Co-administration of SEP and L-Cit limits diabetic cardiomyopathy and ischemia/reperfusion injury in db/db mice through a tetrahydrobiopterin/endothelial nitric oxide synthase/nitric oxide pathway. © 2016 American Heart Association, Inc.

  2. Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI

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    Chandrasekaran Suresh

    2007-02-01

    Full Text Available Abstract Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy.

  3. Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

    Science.gov (United States)

    Yu, Xichun; Tesiram, Yasvir A; Towner, Rheal A; Abbott, Andrew; Patterson, Eugene; Huang, Shijun; Garrett, Marion W; Chandrasekaran, Suresh; Matsuzaki, Satoshi; Szweda, Luke I; Gordon, Brian E; Kem, David C

    2007-01-01

    Background Diabetes is associated with a cardiomyopathy that is independent of coronary artery disease or hypertension. In the present study we used in vivo magnetic resonance imaging (MRI) and echocardiographic techniques to examine and characterize early changes in myocardial function in a mouse model of type 1 diabetes. Methods Diabetes was induced in 8-week old C57BL/6 mice with two intraperitoneal injections of streptozotocin. The blood glucose levels were maintained at 19–25 mmol/l using intermittent low dosages of long acting insulin glargine. MRI and echocardiography were performed at 4 weeks of diabetes (age of 12 weeks) in diabetic mice and age-matched controls. Results After 4 weeks of hyperglycemia one marker of mitochondrial function, NADH oxidase activity, was decreased to 50% of control animals. MRI studies of diabetic mice at 4 weeks demonstrated significant deficits in myocardial morphology and functionality including: a decreased left ventricular (LV) wall thickness, an increased LV end-systolic diameter and volume, a diminished LV ejection fraction and cardiac output, a decreased LV circumferential shortening, and decreased LV peak ejection and filling rates. M-mode echocardiographic and Doppler flow studies of diabetic mice at 4 weeks showed a decreased wall thickening and increased E/A ratio, supporting both systolic and diastolic dysfunction. Conclusion Our study demonstrates that MRI interrogation can identify the onset of diabetic cardiomyopathy in mice with its impaired functional capacity and altered morphology. The MRI technique will lend itself to repetitive study of early changes in cardiac function in small animal models of diabetic cardiomyopathy. PMID:17309798

  4. Protection by dimethyl fumarate against diabetic cardiomyopathy in type 1 diabetic mice likely via activation of nuclear factor erythroid-2 related factor 2.

    Science.gov (United States)

    Hu, Xinyue; Rajesh, Mohanraj; Zhang, Jian; Zhou, Shanshan; Wang, Shudong; Sun, Jian; Tan, Yi; Zheng, Yang; Cai, Lu

    2018-05-01

    Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Early Detection of Subclinical Uremic Cardiomyopathy Using Two-Dimensional Speckle Tracking Echocardiography.

    Science.gov (United States)

    Hassanin, Noha; Alkemary, Alkhateeb

    2016-04-01

    Overhydration has a deleterious effect on cardio myocytes. This study was designated to evaluate left ventricular (LV) systolic and diastolic dysfunction in patients with various stages of chronic kidney disease (CKD) using conventional, tissue Doppler and two-dimensional speckle tracking echocardiography (2DSTE). Forty controls and 90 CKD patients, aged 49.3 ± 14 years old, were enrolled in the study. Patients were divided into 3 groups depending on their glomerular filtration rate. Group 1 (≥60 mL/min per 1.73 m(2) ), group 2 (≤60 mL/min per 1.73 m(2) ), and group 3 (≤60 mL/min per 1.73 m(2) and on regular dialysis for at least 12 months). Pulsed-Doppler and tissue Doppler studies were used to estimate LV filling pressure E/E'. Using 2DSTE, circumferential, radial, and longitudinal functions of the LV have been measured. LV longitudinal systolic strain, early, and late diastolic strain rates were significantly reduced in CKD patients (-16.9 ± 3.8%, 1.6 ± 0.5%, and 1.3 ± 0.4% in CKD vs. -22.5 ± 0.6%, 2.3 ± 0.2%, and 1.9 ± 0.1% in controls, P < 0.001 for all), and no difference was observed in terms of the circumferential LV functions (-22.4 ± 1.7 vs. -22.5 ± 1.4, P = 0.567). Severity of the kidney dysfunction appears to parallel with the rise of E/E' significantly (P < 0.001). In CKD, although the longitudinal and radial systolic functions were reduced, LV ejection fraction may remain within normal limits due to the preservation of the circumferential functions. Early detection of uremic cardiomyopathy might provide useful information for the risk stratification and decide the proper dialysis therapy in these patients. © 2015, Wiley Periodicals, Inc.

  6. Inhibition of advanced glycation endproduct (AGE) rescues against streptozotocin-induced diabetic cardiomyopathy: Role of autophagy and ER stress.

    Science.gov (United States)

    Pei, Zhaohui; Deng, Qinqin; Babcock, Sara A; He, Emily Y; Ren, Jun; Zhang, Yingmei

    2018-03-01

    Diabetes mellitus leads to oxidative stress and contractile dysfunction in the heart. Although several rationales have been speculated, the precise mechanism behind diabetic cardiomyopathy remains elusive. This study was designed to assess the role of inhibition of advanced glycation endproducts (AGE) in streptozotocin (STZ)-induced diabetic cardiac dysfunction. Cardiac contractile function was assessed in normal C57BL/6 and STZ (200mg/kg, single injection and maintained for 2 wks)-induced diabetic mice treated with or without the AGE inhibitor aminoguanidine (50mg/kg/d in drinking water) for 2 weeks using echocardiography and IonOptix MyoCam techniques. Diabetes compromised cardiac contractile function shown as reduced fractional shortening and ejection fraction, enlarged left ventricular end systolic/diastolic diameters, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged shortening and relengthening duration as well as impaired intracellular Ca 2+ homeostasis, the effects of which were alleviated or reversed by aminoguanidine treatment. Diabetes also inhibited autophagy, increased ER stress and phosphorylation of pro-hypertrophic signaling molecules Akt and mTOR, the effect of which was reversed by aminoguanidine. In vitro study revealed that methylglyoxal-derived AGE (MG-AGE) incubation in isolated cardiomyocytes promoted oxidation of sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA2a) and production of superoxide, the effects of which were negated by the autophagy inducer rapamycin, the ER stress chaperone TUDCA or the antioxidant N-acetylcysteine. Taken together, these data revealed that inhibition of AGE formation rescues against experimental diabetes-induced cardiac remodeling and contractile dysfunction possible through regulation of autophagy and ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

    Science.gov (United States)

    Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

    2017-09-01

    The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model

    Directory of Open Access Journals (Sweden)

    Zhiqin Wu

    2014-09-01

    Full Text Available Diabetes mellitus (DM has been recognized as a major health problem. Emodin (Emo has been reported to exhibit protective effects against diabetic nephropathy. However, little has been known about the effect of Emo on diabetic cardiomyopathy (DCM. A type 2 DM model was induced in rats by low dose streptozotocin (STZ combined with high energy intake. We found that Emo-treated groups displayed significantly higher body weight (BW and lower heart weight (HW/BW. Furthermore, Emo could significantly decrease blood glucose, total cholesterol (TG levels, and triglyceride (TC levels in diabetic rats. Moreover, the Emo-treated group showed a marked increase in heart rate (HR and showed lower left ventricular end-diastolic diameter (LVEDD, left ventricular end-systolic diameter (LVESD, left ventricular posterior wall thickness (LWPWT, and interventricular septal diastolic wall thickness (IVSD. Emo induced a significant increase in phosphorylation of Akt and GSK-3β in myocardium. These results suggest that Emo may have great therapeutic potential in the treatment of DCM by Akt/GSK-3β signaling pathway.

  9. Structural neurodegeneration correlates with early diabetic retinopathy

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Hansen, Rasmus Søgaard; Peto, Tunde

    2018-01-01

    PURPOSE: To examine differences in structural and functional neurodegenerative measurements between patients with no and early diabetic retinopathy (DR). METHODS: In this cross-sectional study, we examined 103 patients with type 2 diabetes mellitus. In 7-field fundus photographs acquired...... with Topcon TRC-NW6S, a single, certified grader determined the presence of DR according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral domain optical coherence tomography (OCT) and by a RETI-scan multifocal...... electroretinography (mf-ERG) system in rings 1-6. RESULTS: Median age and duration of diabetes were 63.6 and 10 years, respectively, and 46% were men. Median HbA1c was 50 mmol/mol (6.7%), and ETDRS levels were 10 (41.7%, n = 43), 20 (35.0%, n = 36), and 35 (23.3%, n = 24). The duration of diabetes increased...

  10. Dilated Cardiomyopathy

    Science.gov (United States)

    ... Family history of dilated cardiomyopathy Inflammation of heart muscle from immune system disorders, such as lupus Neuromuscular disorders, such as muscular dystrophy Complications Complications from dilated cardiomyopathy include: Heart ...

  11. Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

    Science.gov (United States)

    de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

    2010-04-01

    The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

  12. Early detection of myocardial dysfunction using two-dimensional speckle tracking echocardiography in a young cat with hypertrophic cardiomyopathy

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    Ryohei Suzuki

    2018-02-01

    Full Text Available Case summary A 5-month-old intact female Scottish Fold cat was presented for cardiac evaluation. Careful auscultation detected a slight systolic murmur (Levine I/VI. The findings of electrocardiography, thoracic radiography, non-invasive blood pressure measurements and conventional echocardiographic studies were unremarkable. However, two-dimensional speckle tracking echocardiography revealed abnormalities in myocardial deformations, including decreased early-to-late diastolic strain rate ratios in longitudinal, radial and circumferential directions, and deteriorated segmental systolic longitudinal strain. At the follow-up examinations, the cat exhibited echocardiographic left ventricular hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional echocardiography. Relevance and novel information This is the first report on the use of two-dimensional speckle tracking echocardiography for the early detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy; the myocardial dysfunction was detected before the development of hypertrophy. The findings from this case suggest that two-dimensional speckle tracking echocardiography can be useful for myocardial assessment when conventional echocardiographic and Doppler findings are ambiguous.

  13. Autologous transplantation of bone marrow mononuclear stem cells by mini-thoracotomy in dilated cardiomyopathy: technique and early results

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    Renato Abdala Karam Kalil

    Full Text Available CONTEXT AND OBJECTIVES: There are few studies concerning bone marrow mononuclear cell (BMMC transplantation in cases of nonischemic dilated cardiomyopathy. This study describes a novel technique of BMMC transplantation and the results up to one year after the procedure. DESIGN AND SETTING: This was a case series to evaluate the safety and viability of the procedure, at Instituto de Cardiologia do Rio Grande do Sul. METHODS: Nine patients with symptomatic dilated cardiomyopathy, functional class III/IV and left ventricular ejection fraction (LVEF < 35% received BMMC (9.6 ± 2.6 x 107 cells at 20 sites in the ventricular wall, by means of thoracotomy of length 5 cm in the fifth left intercostal space. Echocardiograms and nuclear magnetic resonance (NMR were performed. RESULTS: There were no major complications. The functional class results for the first six patients (preoperatively and at two, four, eight and twelve-month follow-ups, respectively were: [IV-2, III-4] to [I-5, II-1] to [I-3, II-3] to [I-2, II-3] and [I-2, II-3]. Echocardiograms showed LVEF: 25.9 ± 8.2; 32.9 ± 10.4; 29.4 ± 7.2; 25.1 ± 7.9; 25.4 ± 6.8% (p = 0.023; and % left ventricular (LV fiber shortening: 12.6 ± 4.4; 16.4 ± 5.4; 14.3 ± 3.7; 12.1 ± 4.0; 12.2 ± 3.4% (p = 0.021. LV performance variation seen on NMR was non-significant. CONCLUSION: Intramyocardial transplantation of BMMC in dilated cardiomyopathy cases is feasible and safe. There were early improvements in symptoms and LV performance. Medium-term evaluation revealed regression of LV function, although maintaining improved functional class.

  14. Exogenous H2S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy

    Science.gov (United States)

    Wu, Jichao; Tian, Zhiliang; Sun, Yu; Lu, Cuicui; Liu, Ning; Gao, Zhaopeng; Zhang, Linxue; Dong, Shiyun; Yang, Fan; Zhong, Xin; Xu, Changqing; Lu, Fanghao; Zhang, Weihua

    2017-01-01

    Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H2S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H2S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H2S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1,4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H2S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H2S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H2S in the context of T2DCM. PMID:28796243

  15. Periodontitis as a possible early sign of diabetes mellitus

    NARCIS (Netherlands)

    Teeuw, Wijnand J.; Kosho, Madeline X. F.; Poland, Dennis C. W.; Gerdes, Victor E. A.; Loos, Bruno G.

    2017-01-01

    The early diagnosis of (pre)diabetes mellitus is essential for the prevention of diabetes complications. It has been suggested that gum disease (periodontitis) might be an early complication of diabetes and may be a useful risk indicator for diabetes screening. Therefore, a dental office could be a

  16. Automated early detection of diabetic retinopathy

    NARCIS (Netherlands)

    Abràmoff, M.D.; Reinhardt, J.M.; Russell, S.R.; Folk, J.C.; Mahajan, V.B.; Niemeijer, M.; Quellec, G.

    2010-01-01

    Purpose To compare the performance of automated diabetic retinopathy (DR) detection, using the algorithm that won the 2009 Retinopathy Online Challenge Competition in 2009, the Challenge2009, against that of the one currently used in EyeCheck, a large computer-aided early DR detection project.

  17. Deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase: a cause of lethal myopathy and cardiomyopathy in early childhood

    NARCIS (Netherlands)

    Rocchiccioli, F.; Wanders, R. J.; Aubourg, P.; Vianey-Liaud, C.; IJlst, L.; Fabre, M.; Cartier, N.; Bougneres, P. F.

    1990-01-01

    A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood beta-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's

  18. High-Intensity Exercise Reduces Cardiac Fibrosis and Hypertrophy but Does Not Restore the Nitroso-Redox Imbalance in Diabetic Cardiomyopathy

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    Ulises Novoa

    2017-01-01

    Full Text Available Diabetic cardiomyopathy refers to the manifestations in the heart as a result of altered glucose homeostasis, reflected as fibrosis, cellular hypertrophy, increased oxidative stress, and apoptosis, leading to ventricular dysfunction. Since physical exercise has been indicated as cardioprotective, we tested the hypothesis that high-intensity exercise training could reverse the cardiac maladaptations produced by diabetes. For this, diabetes was induced in rats by a single dose of alloxan. Diabetic rats were randomly assigned to a sedentary group or submitted to a program of exercise on a treadmill for 4 weeks at 80% of maximal performance. Another group of normoglycemic rats was used as control. Diabetic rat hearts presented cardiomyocyte hypertrophy and interstitial fibrosis. Chronic exercise reduced both parameters but increased apoptosis. Diabetes increased the myocardial levels of the mRNA and proteins of NADPH oxidases NOX2 and NOX4. These altered levels were not reduced by exercise. Diabetes also increased the level of uncoupled endothelial nitric oxide synthase (eNOS that was not reversed by exercise. Finally, diabetic rats showed a lower degree of phosphorylated phospholamban and reduced levels of SERCA2 that were not restored by high-intensity exercise. These results suggest that high-intensity chronic exercise was able to reverse remodeling in the diabetic heart but was unable to restore the nitroso-redox imbalance imposed by diabetes.

  19. Early determinants of type-2 diabetes.

    Science.gov (United States)

    Berends, L M; Ozanne, S E

    2012-10-01

    The global prevalence of type-2 diabetes (T2D) has more than doubled in the last 30 years and is predicted to continue to rise at an alarming rate. The associated health and financial burdens are considerable. The aetiology of common forms of T2D is multifactorial and involves a complex interplay between genetic, epigenetic and environmental factors. The influential role of the environment, in particular our diet and sedentary lifestyles, in diabetes risk is well established. Of major concern is the increasing prevalence of early onset T2D or pre-diabetic characteristics in children. In recent years, the role of the early life environment in programming diabetes risk has been the focus of numerous human and animal studies. Historical studies highlighted an association between low birthweight, a proxy for suboptimal in utero growth, and diabetes risk in adulthood. Over more recent years it has become apparent that a variety of expositions, including maternal obesity and/or maternal diabetes, can have a significant effect on offspring health outcomes. Further complicating matters, paternal and transgenerational transmission of T2D can occur thus mediating a perpetuating cycle of disease risk between generations. It is imperative for the underlying mechanisms to be elucidated so that interventions can be introduced. In doing so, it may be possible to prevent, delay or reverse a pre-programmed risk for T2D induced by pre- and/or postnatal environmental factors to improve health outcomes and curb premature metabolic decline. This review presents evidence for how the early life environment may programme T2D risk and suggests some mechanisms by which this may occur. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Altered contractile response due to increased beta3-adrenoceptor stimulation in diabetic cardiomyopathy: the role of nitric oxide synthase 1-derived nitric oxide.

    Science.gov (United States)

    Amour, Julien; Loyer, Xavier; Le Guen, Morgan; Mabrouk, Nejma; David, Jean-Stéphane; Camors, Emmanuel; Carusio, Nunzia; Vivien, Benoît; Andriantsitohaina, Ramaroson; Heymes, Christophe; Riou, Bruno

    2007-09-01

    In the diabetic heart, the positive inotropic response to beta-adrenoceptor stimulation is altered and beta1 and beta2 adrenoceptors are down-regulated, whereas beta3 adrenoceptor is up-regulated. In heart failure, beta3-adrenoceptor stimulation induces a negative inotropic effect that results from endothelial nitric oxide synthase (NOS3)-derived nitric oxide production. The objective of our study was to investigate the role of beta3-adrenoceptor in diabetic cardiomyopathy. beta-Adrenergic responses were investigated in vivo (dobutamine echocardiography) and in vitro (left ventricular papillary muscle) in healthy and streptozotocin-induced diabetic rats. The effect of beta3-adrenoceptor inhibition on the inotropic response was studied in vitro. Immunoblots and NOS activities were performed in heart homogenates (electron paramagnetic resonance) and isolated cardiomyocytes. Data are mean percentage of baseline +/- SD. The impaired positive inotropic effect was confirmed in diabetes both in vivo (121 +/- 15% vs. 160 +/- 16%; P < 0.05) and in vitro (112 +/- 5% vs. 179 +/- 15%; P < 0.05). In healthy rat, the positive inotropic effect was not significantly modified in presence of beta3-adrenoceptor antagonist (174 +/- 20%), nonselective NOS inhibitor (N -nitro-l-arginine methylester [l-NAME]; 183 +/- 19%), or selective NOS1 inhibitor (vinyl-l-N-5-(1-imino-3-butenyl)-l-ornithine [l-VNIO]; 172 +/- 13%). In diabetes, in parallel with the increase in beta3-adrenoceptor protein expression, the positive inotropic effect was partially restored by beta3-adrenoceptor antagonist (137 +/- 8%; P < 0.05), l-NAME (133 +/- 11%; P < 0.05), or l-VNIO (130 +/- 13%; P < 0.05). Nitric oxide was exclusively produced by NOS1 within diabetic cardiomyocytes. NOS2 and NOS3 proteins were undetectable. beta3-Adrenoceptor is involved in altered positive inotropic response to beta-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by NOS1-derived nitric oxide in diabetic

  1. The effect of maternal gestational diabetes and HbA1c on hypertrophic cardiomyopathy of infants

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    Hoda Rezaie

    2017-09-01

    Methods: This case-control study was performed on 60 neonates born in Afzalipour Hospital (Kerman University of Medical Sciences from May to November 2014 in two groups of eligible infants using the convenience sampling method. Information about the age, sex, weight, gestational age, maternal age, obstetric history, gestational diabetes through the checklist were collected. Then Doppler echocardiography, M- Mode, Doppler tissue was conducted on two groups. Echocardiographic criteria including ventricular septal thickness and blood HbA1c mothers in both groups were compared. To compare quantitative and qualitative variables between the two groups’ Independent samples t‐test and Chi-square test was used. A significant level of 0.05 was considered in all of the statistical samples and SPSS software, ver. 20 (IBM, Armonk, NY, USA was used to analyze the data. Results: In this study, the birth weight of infants and the age of mothers did not differ between two groups (Respectively P=0.56, P=0.08 However, HbA1c was significantly higher in the infants of mothers with impaired glucose tolerance test (GTT (P<0.001. In infants of mothers with impaired GTT, ventricular septal thickness was significantly higher than the healthy controls (P=0.03, Also there was a significant difference between two groups in tissue Doppler criteria (Ea (P=0.04, In other echocardiographic criteria, no significant differences were reported (The LA/AO, LVPWT, LVEF, LVEF, LVFS, LVFS, LVEDd, LVESd, Sa and Aa, All P-values were ≥ 0.05. Conclusion: Diabetes mellitus of mothers causes several complications in their infants. The prevalence of cardiomyopathy hypertrophy is higher in babies whose mothers have higher levels of HbA1c and a sign of poor control of blodd glucose level during pregnancy.

  2. Early phacoemulsification in diabetic cataract for early recognition and management of diabetic macular oedema

    International Nuclear Information System (INIS)

    Wahab, S.; Rab, K. F. U.; Hargun, L. D.

    2013-01-01

    Objective: To get optimal visualization of fundus by early phacoemulsification in diabetic cataract for early recognition and management of diabetic macular oedema. Study Design: Interventional study. Place and Duration of Study: Ophthalmology Unit III, Sindh Government Lyari General Hospital and Dow University of Health Sciences and Al-Noor Eye Hospital, Karachi, from July 2008 to June 2009. Methodology: Patients with uncontrolled type-II diabetes mellitus of more than 10 years of duration were selected. Patients with clinical significant macular oedema (CSME), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were excluded. Follow-up was done on day 1, 1 week, 1 month, 3 months and 6 months. Results: The male to female ratio was 1:1.44. Out of 218 patients; 129 (59.2%) were males and 89 (40.8%) were females. CSME was found in 82 patients (37.6%) at first postoperative week which declined to 29 cases (13.3%) at first month follow-up. Three subjects developed mild to moderate NPDR. In majority of the subjects, best corrected visual acuity (BCVA) gradually improved in each subsequent follow-up visit. Conclusion: Early phacoemulsification in diabetic cataract offers optimal posterior pole visualization and clears the ambiguity of decreased vision either caused by cataract or macular oedema. Uncomplicated phacoemulsification does not accelerate diabetic macular oedema or retinopathy provided glycemic control and co-morbids are well addressed. (author)

  3. A Crude 1-DNJ Extract from Home Made Bombyx Batryticatus Inhibits Diabetic Cardiomyopathy-Associated Fibrosis in db/db Mice and Reduces Protein N-Glycosylation Levels

    Directory of Open Access Journals (Sweden)

    Qing Zhao

    2018-06-01

    Full Text Available The traditional Chinese drug Bombyx Batryticatus (BB, which is also named the white stiff silkworm, has been widely used in Chinese clinics for thousands of years. It is famous for its antispasmodic and blood circulation-promoting effects. Cardiomyocyte hypertrophy, interstitial cell hyperplasia, and myocardial fibrosis are closely related to the N-glycosylation of key proteins. To examine the alterations of N-glycosylation that occur in diabetic myocardium during the early stage of the disease, and to clarify the therapeutic effect of 1-Deoxynojirimycin (1-DNJ extracted from BB, we used the db/db (diabetic mouse model and an approach based on hydrophilic chromatography solid-phase extraction integrated with an liquid Chromatograph Mass Spectrometer (LC-MS identification strategy to perform a site-specific N-glycosylation analysis of left ventricular cardiomyocyte proteins. Advanced glycation end products (AGEs, hydroxyproline, connective tissue growth factor (CTGF, and other serum biochemical indicators were measured with enzyme-linked immunosorbent assays (ELISA. In addition, the α-1,6-fucosylation of N-glycans was profiled with lens culinaris agglutinin (LCA lectin blots and fluorescein isothiocyanate (FITC-labelled lectin affinity histochemistry. The results indicated that 1-DNJ administration obviously downregulated myocardium protein N-glycosylation in db/db mice. The expression levels of serum indicators and fibrosis-related cytokines were reduced significantly by 1-DNJ in a dose-dependent manner. The glycan α-1,6-fucosylation level of the db/db mouse myocardium was elevated, and the intervention effect of 1-DNJ administration on N-glycan α-1,6-fucosylation was significant. To verify this result, the well-known transforming growth factor-β (TGF-β/Smad2/3 pathway was selected, and core α-1,6-fucosylated TGF-β receptor II (TGFR-βII was analysed semi-quantitatively with western blotting. The result supported the conclusions obtained

  4. L-glutamine supplementation prevents the development of experimental diabetic cardiomyopathy in streptozotocin-nicotinamide induced diabetic rats.

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    Sachin L Badole

    Full Text Available The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg. Nicotinamide (100 mg/kg, i.p. was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o., II: diabetic control (distilled water, 10 ml/kg, p.o., III: L-glutamine (500 mg/kg, p.o. and IV: L-glutamine (1000 mg/kg, p.o.. All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

  5. Dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Salvatore, M.; Cuocolo, A.

    1988-01-01

    Radionuclide techniques are easily obtainable, noninvasive examinations that provide useful information in the evaluation, diagnosis and management of patients with dilated cardiomyopathy. The gated blood pool scan allows the assessment of ventricular size, configuration, and wall and septal thickness. These data allow the functional class of the cardiomyopathy (congestive, restrictive or hypertrophic) to be defined. Often THallium-201 myocardial perfusion imaging adds further information and is particularly useful in distinguishing congestive cardiomyopathy from severe coronary artery disease and in depicting septal abnormalities in hipertrophic cardiomyopathy. Useful as these techniques are, they are not substitutes for conventional approaches to diagnosis. Careful history taking and physical examination, as well as scrutiny of the electrocardiogram, chest X-ray and echocardiogram should be standard practice for the evaluation of patients with suspected cardiomyopathy. Judicious use of noninvasive techniques may obviate the need for cardiac catheterization in many patients

  6. Beneficial Role of Some Natural Products to Attenuate the Diabetic Cardiomyopathy Through Nrf2 Pathway in Cell Culture and Animal Models.

    Science.gov (United States)

    Sathibabu Uddandrao, V V; Brahmanaidu, Parim; Nivedha, P R; Vadivukkarasi, S; Saravanan, Ganapathy

    2017-10-27

    Diabetic cardiomyopathy, as one of the main cardiac complications in diabetic patients, is identified to connect with oxidative stress that is due to interruption in balance between reactive oxygen species or/and reactive nitrogen species generation and their clearance by antioxidant protection systems. Transcription factor the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in maintaining the oxidative homeostasis by regulating multiple downstream antioxidants. The Nrf2 plays a significant role in ARE-mediated basal and inducible expression of more than 200 genes that can be grouped into numerous categories as well as antioxidant genes and phase II detoxifying enzymes. On the other hand, activation of Nrf2 by natural and synthetic therapeutics or antioxidants has been revealed effective for the prevention and treatment of toxicities and diseases connected with oxidative stress. Hence, recently focus has been shifted toward plants and plant-based medicines in curing such chronic diseases, as they are supposed to be less toxic. In this review, we focused on the role of some natural products on diabetic cardiomyopathy through Nrf2 pathway.

  7. Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

    Science.gov (United States)

    Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

    2015-03-01

    Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

  8. Pacing-induced Cardiomyopathy

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    Alex Koo

    2017-10-01

    Full Text Available We present a case of pacing-induced cardiomyopathy. The patient presented with clinical symptoms of dyspnea, leg swelling, and orthopnea several months after a dual-chambered pacemaker was placed for third-degree heart block. The echocardiogram demonstrated a depressed ejection fraction. Coronary angiography was performed, which showed widely patent vessels. Single- and dual-chambered pacemakers create ventricular dyssynchrony, which in turn can cause structural, molecular changes leading to cardiomyopathy. With early intervention of biventricular pacemaker replacement, these changes can be reversible; thus, a timely diagnosis and awareness is warranted.

  9. Restrictive cardiomyopathy

    Science.gov (United States)

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  10. Peripartum Cardiomyopathy

    Science.gov (United States)

    ... short- ness of breath, and palpitations. •  Electrocardiogram (heart tracing) to assess heart rate and rhythm, to look ... Accessed January 22, 2013. The Peripartum Cardiomyopathy Network Web site. http: / / www. peripartumcmnetwork. pitt. edu. Accessed January ...

  11. Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

    2013-01-01

    Full Text Available Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal or high-fat diet (obese. Obese animals received the vehicle (obese, a single dose (obese + 1x MSC or three doses (obese + 3x MSC of 0.5x10(6 syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy

  12. Mitochondrial cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Ayman W. El-Hattab

    2016-07-01

    Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  13. Oxidative stress tolerance of early stage diabetic endothelial progenitor cell

    Directory of Open Access Journals (Sweden)

    Dewi Sukmawati

    2015-06-01

    Conclusions: Primitive BM-EPCs showed vasculogenic dysfunction in early diabetes. However the oxidative stress is not denoted as the major initiating factor of its cause. Our results suggest that primitive BM-KSL cell has the ability to compensate oxidative stress levels in early diabetes by increasing the expression of anti-oxidative enzymes.

  14. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death.

    Science.gov (United States)

    Cao, Siqi; Smith, Laura L; Padilla-Lopez, Sergio R; Guida, Brandon S; Blume, Elizabeth; Shi, Jiahai; Morton, Sarah U; Brownstein, Catherine A; Beggs, Alan H; Kruer, Michael C; Agrawal, Pankaj B

    2017-09-15

    Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development and function is unclear. There have been several reports linking de novo dominant EEF1A2 mutations to neurological issues in humans. We report a pair of siblings carrying a homozygous missense mutation p.P333L in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation. Functional genomic analysis was performed in S. cerevisiae and zebrafish. In S. cerevisiae, there was no evidence for a dominant-negative effect. Previously identified putative de novo mutations failed to complement yeast strains lacking the EEF1A ortholog showing a major growth defect. In contrast, the introduction of the mutation seen in our family led to a milder growth defect. To evaluate its function in zebrafish, we knocked down eef1a2 expression using translation blocking and splice-site interfering morpholinos. EEF1A2-deficient zebrafish had skeletal muscle weakness, cardiac failure and small heads. Human EEF1A2 wild-type mRNA successfully rescued the morphant phenotype, but mutant RNA did not. Overall, EEF1A2 appears to be critical for normal heart function in humans, and its deficiency results in clinical abnormalities in neurologic function as well as in skeletal and cardiac muscle defects. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Restrictive Cardiomyopathy

    Science.gov (United States)

    ... up in the circulatory system. In time, the heart fails. What causes it? Restrictive cardiomyopathy is often caused by diseases in other parts of the body. One known cause is cardiac ... build up in the heart tissue, making the tissue stiff and thickened. Cardiac ...

  16. GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish

    NARCIS (Netherlands)

    Jiménez-Amilburu, Vanesa; Jong-Raadsen, Susanne; Bakkers, Jeroen; Spaink, Herman P.; Marín-Juez, Rubén

    2015-01-01

    Cardiomyopathies-associated metabolic pathologies (e.g., type 2 diabetes and insulin resistance) are a leading cause of mortality. It is known that the association between these pathologies works in both directions, for which heart failure can lead to metabolic derangements such as insulin

  17. GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish

    NARCIS (Netherlands)

    Jiménez-Amilburu, Vanesa; Jong-Raadsen, Susanne; Bakkers, Jeroen; Spaink, Herman P; Marín-Juez, Rubén

    Cardiomyopathies-associated metabolic pathologies (e.g., type 2 diabetes and insulin resistance) are a leading cause of mortality. It is known that the association between these pathologies works in both directions, for which heart failure can lead to metabolic derangements such as insulin

  18. Tissue Doppler Imaging Combined with Advanced 12-Lead ECG Analysis Might Improve Early Diagnosis of Hypertrophic Cardiomyopathy in Childhood

    Science.gov (United States)

    Femlund, E.; Schlegel, T.; Liuba, P.

    2011-01-01

    Optimization of early diagnosis of childhood hypertrophic cardiomyopathy (HCM) is essential in lowering the risk of HCM complications. Standard echocardiography (ECHO) has shown to be less sensitive in this regard. In this study, we sought to assess whether spatial QRS-T angle deviation, which has shown to predict HCM in adults with high sensitivity, and myocardial Tissue Doppler Imaging (TDI) could be additional tools in early diagnosis of HCM in childhood. Methods: Children and adolescents with familial HCM (n=10, median age 16, range 5-27 years), and without obvious hypertrophy but with heredity for HCM (n=12, median age 16, range 4-25 years, HCM or sudden death with autopsy-verified HCM in greater than or equal to 1 first-degree relative, HCM-risk) were additionally investigated with TDI and advanced 12-lead ECG analysis using Cardiax(Registered trademark) (IMED Co Ltd, Budapest, Hungary and Houston). Spatial QRS-T angle (SA) was derived from Kors regression-related transformation. Healthy age-matched controls (n=21) were also studied. All participants underwent thorough clinical examination. Results: Spatial QRS-T angle (Figure/ Panel A) and septal E/Ea ratio (Figure/Panel B) were most increased in HCM group as compared to the HCM-risk and control groups (p less than 0.05). Of note, these 2 variables showed a trend toward higher levels in HCM-risk group than in control group (p=0.05 for E/Ea and 0.06 for QRS/T by ANOVA). In a logistic regression model, increased SA and septal E/Ea ratio appeared to significantly predict both the disease (Chi-square in HCM group: 9 and 5, respectively, p less than 0.05 for both) and the risk for HCM (Chi-square in HCM-risk group: 5 and 4 respectively, p less than 0.05 for both), with further increased predictability level when these 2 variables were combined (Chi-square 10 in HCM group, and 7 in HCM-risk group, p less than 0.01 for both). Conclusions: In this small material, Tissue Doppler Imaging and spatial mean QRS-T angle

  19. Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

    Science.gov (United States)

    Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

    2017-09-01

    Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

  20. Early transcriptional alteration of histone deacetylases in a murine model of doxorubicin-induced cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Izabela Piotrowska

    Full Text Available Doxorubicin is a potent chemotherapeutic agent that is widely-used to treat a variety of cancers but causes acute and chronic cardiac injury, severely limiting its use. Clinically, the acute side effects of doxorubicin are mostly manageable, whereas the delayed consequences can lead to life-threatening heart failure, even decades after cancer treatment. The cardiotoxicity of doxorubicin is subject to a critical cumulative dose and so dosage limitation is considered to be the best way to reduce these effects. Hence, a number of studies have defined a "safe dose" of the drug, both in animal models and clinical settings, with the aim of avoiding long-term cardiac effects. Here we show that a dose generally considered as safe in a mouse model can induce harmful changes in the myocardium, as early as 2 weeks after infusion. The adverse changes include the development of fibrotic lesions, disarray of cardiomyocytes and a major transcription dysregulation. Importantly, low-dose doxorubicin caused specific changes in the transcriptional profile of several histone deacetylases (HDACs which are epigenetic regulators of cardiac remodelling. This suggests that cardioprotective therapies, aimed at modulating HDACs during doxorubicin treatment, deserve further exploration.

  1. Early insulin therapy in patients with type 2 diabetes mellitus

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (T2DM) is an insulin-insufficient disease characterised ... complications.1–4 Early in the onset of T2DM there is development of relative insulin ..... position statement of the American Diabetes Association (ADA) and.

  2. Macular micropseudocysts in early stages of diabetic retinopathy.

    Science.gov (United States)

    Tremolada, Gemma; Pierro, Luisa; de Benedetto, Umberto; Margari, Sergio; Gagliardi, Marco; Maestranzi, Gisella; Calori, Giliola; Lorenzi, Mara; Lattanzio, Rosangela

    2011-01-01

    To identify by noninvasive means early retinal abnormalities that may predict diabetic macular edema. The authors analyzed retrospectively data from consecutive patients with Type 1 (n = 16) or Type 2 (n = 23) diabetes who presented for routine follow-up of early retinopathy, had no clinical signs or symptoms of diabetic macular edema, and were evaluated with spectral-domain optical coherence tomography. Age- and gender-matched nondiabetic subjects provided normative data. Spectral-domain optical coherence tomography revealed in the macular region of diabetic patients small hyporeflective areas (median diameter, 55 μm) contained within discrete retinal layers that we named micropseudocysts (MPCs). Micropseudocysts are associated with vascular leakage. The patients showing MPCs had more frequently systemic hypertension and increased central foveal thickness than those without MPCs. The association with increased central foveal thickness was only in the patients with Type 2 diabetes. Macular MPCs in patients with mild diabetic retinopathy appear to reflect leakage and can precede macular thickening. The association of MPCs with increased central foveal thickness in patients with Type 2 diabetes, but not in patients with Type 1 diabetes, points to a greater tendency to retinal fluid accumulation in patients with Type 2 diabetes. Studies in larger cohorts will determine the usefulness of MPCs in strategies to abort diabetic macular edema.

  3. Takotsubo cardiomyopathy

    DEFF Research Database (Denmark)

    Nielsen, Lene Hüche; Munk, Kim; Goetzsche, Ole

    2009-01-01

    INTRODUCTION: Sparse information with regard to the electrocardiographic (ECG) changes in Takotsubo cardiomyopathy (TC) is available. The purpose of this study was to describe the clinical characteristics and electrocardiographic changes in a Danish cohort of patients with TC. We discuss the pote......INTRODUCTION: Sparse information with regard to the electrocardiographic (ECG) changes in Takotsubo cardiomyopathy (TC) is available. The purpose of this study was to describe the clinical characteristics and electrocardiographic changes in a Danish cohort of patients with TC. We discuss...... retrospectively from medical records and the hospitals laboratory database. RESULTS: Seven patients with TC were identified comprising six females and one male (mean age 70, range 53-81 years). In the acute phase all patients had ECG changes compatible with ST-elevation acute myocardial infarction (STEMI...

  4. Early diagnosis of diabetic retinopathy in primary care.

    Science.gov (United States)

    Jimenez-Baez, Maria Valeria; Marquez-Gonzalez, Horacio; Barcenas-Contreras, Rodolfo; Morales Montoya, Carlos; Espinosa-Garcia, Laura Fatima

    2015-01-01

    To evaluate the impact of a strategy for early detection of diabetic retinopathy in patients with type 2 diabetes mellitus (DMT2) in Quintana Roo, México. Study transversal, observational, prospective, analytical, eight primary care units from Mexican Social Security Institute in the northern delegation of the State of Quintana Roo, Mexico were included. A program for early detection of diabetic retinopathy (DR) in adult 376,169 was designed. Were diagnosed 683 cases of type 2 diabetes, in 105 patients randomized was conducted to direct ophthalmoscopy were subjected to a secondary hospital were assigned. Will determine the degree of diabetic retinopathy and macular edema was performed. In population were 55.2% female, mean age 48+11.1 years, 23.8 % had some degree of DR, 28.0% with mild non- proliferative diabetic retinopathy 48.0 % moderate 16.0% and severe and 8.0% showed proliferative diabetic retinopathy. Those over age 30 are 2.8 times more risk of developing DR, OR= 2.8; 95%CI: 0.42-18.0, and OR= 1.7; 95%CI: 1.02-2.95 women. The implementation of programs aimed at the early detection of debilitating conditions such as diabetic retinopathy health impact beneficiaries, effective links between primary care systems and provide second level positive health outcomes for patient diseases.

  5. Early interventions to prevent retinal vasculopathy in diabetes: a review

    Directory of Open Access Journals (Sweden)

    Harrison WW

    2015-08-01

    Full Text Available Wendy W Harrison, Vladimir YevseyenkovArizona College of Optometry, Midwestern University, Glendale, AZ, USAAbstract: Diabetic eye disease is a public health concern in all areas of the world as a leading cause of blindness in the working aged to elderly populations. Diabetes damages the lining of the microvasculature throughout the body through prolonged exposure to hyperglycemic conditions. The ocular changes are progressive with very little recourse for improvement once damage begins. Current treatments for the eye focus mainly on the late stages of the disease when neovascularization or edema threatens sight. Early interventions for diabetic vasculopathy involve metabolic therapy to improve blood glucose and blood pressure control. Technology improvements have a large part to play in advancing diagnosis of diabetic eye disease. These new technologies offer both structural and functional means for assessment of retinal health. This review focuses on current treatments for diabetic eye disease at all stages with an emphasis on new and early interventions. It also details established and emerging technologies used for earlier detection of diabetic eye disease, which is vital to the development and approval of much needed treatments targeted at earlier stages of diabetic retinopathy. Possible future treatments should be aimed to prevent retinal vasculopathy from progressing. This review will explore current research on this topic and what is needed moving forward.Keywords: diabetes, diabetic retinopathy, vascular disease

  6. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: a randomised, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Raman, Subha V; Hor, Kan N; Mazur, Wojciech; Halnon, Nancy J; Kissel, John T; He, Xin; Tran, Tam; Smart, Suzanne; McCarthy, Beth; Taylor, Michael D; Jefferies, John L; Rafael-Fortney, Jill A; Lowe, Jeovanna; Roble, Sharon L; Cripe, Linda H

    2015-02-01

    Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1·0 [IQR 0·3-2·2] vs 2·2 [1·3-3·1]; p=0·020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in

  7. Associations between follow-up screening after gestational diabetes and early detection of diabetes

    DEFF Research Database (Denmark)

    Olesen, Christinna Rebecca; Hyldgaard Nielsen, Jane; Mortensen, Rikke Nørmark

    2016-01-01

    BACKGROUND: Women whose pregnancy was complicated by gestational diabetes have a 7-fold higher risk of developing diabetes, primarily type 2. Early detection can prevent or delay the onset of late complications, for which follow-up screening is important. This study investigated the extent...... of participation in follow-up screening and the possible consequences of nonattendance in the Region of North Jutland, Denmark. METHOD: In Danish national registers covering the years 1994-2011 we identified 2171 birthing women whose pregnancy was complicated by first-time gestational diabetes. Control visits...... and treatment after gestational diabetes than women not attending. The results for women attending testing at biochemical departments also showed an increased risk of initiation of treatment. Women attending at least one general practitioners control had a significantly higher risk of early diabetes diagnosis...

  8. Quantitative assessment of early diabetic retinopathy using fractal analysis.

    Science.gov (United States)

    Cheung, Ning; Donaghue, Kim C; Liew, Gerald; Rogers, Sophie L; Wang, Jie Jin; Lim, Shueh-Wen; Jenkins, Alicia J; Hsu, Wynne; Li Lee, Mong; Wong, Tien Y

    2009-01-01

    Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

  9. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  10. Role of early screening for diabetic retinopathy in patients with diabetes mellitus: An overview

    Directory of Open Access Journals (Sweden)

    Praveen Vashist

    2011-01-01

    Full Text Available Diabetes has emerged as a major public health problem in India. It is estimated that there were 40 million persons with diabetes in India in 2007 and this number is predicted to rise to almost 70 million by 2025. The impact of rapid urbanization, industrialization and lifestyle changes has led to an increasing trend in prevalence of diabetes and its associated complications such as neuropathy, nephropathy, vascular diseases (cardiac, cerebral and peripheral and retinopathy. Diabetic retinopathy is a important cause of avoidable blindness in India. Treatment interventions at early stages of diabetic retinopathy can reduce burden of blindness due to diabetic retinopathy. With the available cost-effective methods of early screening, appropriate strategies/models need to be developed. Such models need to have a well-developed mode for screening, diagnosis and referral at each hierarchal level beginning from primary health centers to specialized institutes for eye care. The National Program for Control of Blindness of India recommends opportunistic screening for identification of diabetic retinopathy. Every opportunity of contact with high-risk cases for diabetes and/or diabetic retinopathy should be utilized for screening, diagnosis and referral. All the stakeholders including the private sector will need to play a role. Along with this, awareness generation and behavior change amongst the diabetics and care support systems should also be part of the overall model. A major role can be played by community participation and improving the health seeking behavior among diabetics in order to reach a larger population and increasing the compliance for continued care.

  11. Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsutamoto, Takayoshi; Ibe, Kunihiro [Toyosato Hospital, Toyosato, Shiga (Japan); Sakai, Hiroshi; Yamaji, Masayuki; Kawahara, Chiho; Nakae, Ichiro; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru [Shiga Univ. of Medical Science, Faculty of Medicine, Otsu, Shiga (Japan)

    2011-08-15

    Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18{+-}0.4 vs. 2.36{+-}0.4, P<0.0001), and the washout rate was significantly decreased (34.8{+-}5.7 vs. 32.6{+-}6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729{+-}858 vs. 558{+-}747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author)

  12. Biomarker for early renal microvascular and diabetic kidney diseases.

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  13. Eplerenone for early cardiomyopathy in Duchenne muscular dystrophy: results of a two-year open-label extension trial

    Directory of Open Access Journals (Sweden)

    Subha V. Raman

    2017-02-01

    Full Text Available Abstract Background Cardiomyopathy is a leading cause of morbidity and mortality in boys with Duchenne muscular dystrophy (DMD. We recently showed in a 12-month double-blind randomized controlled trial that adding eplerenone to background medical therapy was cardioprotective in this population. The objective of this study was to evaluate the safety and efficacy of longer-term eplerenone therapy in boys with DMD. Results Eleven subjects (phase 1 baseline median [range] age: 13 [7 – 25] years from the original 12-month trial at a single participating center were enrolled. Importantly, those who entered the extension study who had been on eplerenone previously were significantly older than those who had originally been on placebo (median age 10.5 vs. 18.0 years, p = 0.045. During an additional 24-month open-label extension study, all boys received eplerenone 25 mg orally once daily to treat preclinical DMD cardiomyopathy, defined as evident myocardial damage by late gadolinium enhancement cardiac magnetic resonance (LGE with preserved ejection fraction (EF. The threshold for potassium level, the primary safety measure, was not exceeded in any non-hemolyzed blood sample. Over 24 months, left ventricular (LV systolic strain, a more sensitive marker whose more negative values indicate greater contractility significantly improved (median change -4.4%, IQR -5.8 to -0.9% in younger subjects whereas older subjects’ strain remained stable without significant worsening or improvement (median change 0.2%, IQR -1.1 to 4.3%. EF and extent of myocardial damage by LGE remained stable in both groups over 2 years. Conclusions Eplerenone offers effective and safe cardioprotection for boys with DMD, particularly when started at a younger age. Eplerenone is a useful clinical therapeutic option, particularly if treatment is initiated earlier in life when cardiac damage is minimal. Trial registration http://ClinicalTrials.gov identifier NCT01521546

  14. Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.

    Science.gov (United States)

    Tsuda, Takeshi; Fitzgerald, Kristi; Scavena, Mena; Gidding, Samuel; Cox, Mary O; Marks, Harold; Flanigan, Kevin M; Moore, Steven A

    2015-03-01

    We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.

  15. MR imaging in cardiomyopathies

    International Nuclear Information System (INIS)

    Miller, S.; Riessen, R.

    2005-01-01

    According to the WHO classification, cardiomyopathies are a group of diseases which are associated with myocardial dysfunction and can be classified either as primary or secondary cardiomyopathies. Genetic disorders have been identified in certain primary cardiomyopathies, however often the etiology remains unknown. The term ''secondary cardiomyopathy'' is used to specify diseases with the clinical indications of a cardiomyopathy, but can be attributed to a certain pathophysiological mechanism such as exposure to toxic substances, metabolic syndromes or systemic diseases. Based on morphological and functional criteria, primary cardiomyopathies are divided into dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and restrictive cardiomyopathy (RCM). During the last two decades MR imaging has emerged to a well established diagnostic tool for the understanding and treatment of cardiomyopathies. Morphological and functional information can be achieved with a high level of accuracy and reproducibility. Tissue alteration of the myocardium can be detected assessing regional contrast enhancement, T1- and T2-signal intensities and chemical shift phenomena. This article describes characteristic aspects of MR imaging for the diagnosis of primary and secondary cardiomyopathies. (orig.)

  16. Early diagnosis of sub-clinical stage of diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Xing-Hui Xu

    2014-12-01

    Full Text Available AIM: To evaluate the early diagnosis of sub-clinic stage of diabetic retinopathy.METHODS: This was cross sectional study,multifocal retina electroretinogram(mf-ERG, contrast sensitivity(CSand central retinal artery color Doppler examination were recorded from 30 cases(30 eyesmatched control subjects, 35 cases(35 eyeswith type 2 diabetes mellitus(DMwithout diabetic retinopathy(NDRand 38 cases(38 eyeswith non-prolifera tive diabetic retinopathy(NPDR. One-way ANOVA and SNK-q test were used for data analysis.RESULTS: P1 response density of NDR patients were found decrease, N1 implicit time were delayed. Which were related with the degree of retinopathy(PPPP>0.05, The differences between normal group, NDR group and NPDR group were found statistically significant(PCONCLUSION: mf-ERG and CS are sensitive indexes for early evaluation of visual function in patients with diabetes mellitus, with development of the disease, CRA blood flow also appears to decline.

  17. Peripartum cardiomyopathy

    International Nuclear Information System (INIS)

    Velasquez V, Jorge E; Duque R, Mauricio

    2008-01-01

    Peripartum cardiomyopathy is a clinical entity with a variable frequency according to the zone of the study. It is characterized by a systolic dysfunction of the left ventricle and posterior appearance of heart failure symptoms that occur during the last month of pregnancy and the first post-partum months. Its etiology isn't still clear, but different theories are proposed based on inflammatory, infectious and autoimmune processes. Alterations related to oxidative stress that could largely explain this pathology were recently described. Its clinical presentation has a big similitude with all other causes of heart failure although atypical presentations have been described. Its diagnosis requires a high suspicion level and must be considered in any woman with symptoms of heart failure during the peripartum. The conventional treatment of chronic heart failure that includes beta-blockers, angiotensin converting enzyme inhibitors and diuretics, in addition to the advances in diagnosis and management of acute heart failure, allowed changing the history of the disease by lowering mortality and recovering systolic function of the left ventricle. Gestations posterior to the development of this entity will depend on the complete recovery of heart function without lowering the risk of recurrence. There still remain many questions to answer in areas like etiology, risk factors, treatment and prognosis markers that may allow to prevent and to manage in an appropriate and safe way both the mother and her son.

  18. Early risk stratification in pediatric type 1 diabetes

    DEFF Research Database (Denmark)

    Broe, Rebecca

    2015-01-01

    In the late 1980s all Danish children with type 1 diabetes were invited for a nationwide evaluation of glycemic control. Approximately 75% (n = 720) participated and have later been referred to as The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). The results were surprisingly poor glycemic...... control among these young patients which lead to a great emphasis on glycemic control in the Danish Pediatric Departments. In 1995 the participants were invited for yet another evaluation but this time with main focus on early signs of microvascular complications - 339 participated. The mean HbA1c had...

  19. Electrogastrography abnormalities appear early in children with diabetes type 1.

    Science.gov (United States)

    Posfay-Barbe, Klara M; Lindley, Keith J; Schwitzgebel, Valérie M; Belli, Dominique C; Schäppi, Michela G

    2011-10-01

    The objective of the study was to evaluate gastric myoelectrical activity in young patients with diabetes and to correlate it with their metabolic control [fasting blood glucose, glycosylated haemoglobin, and fructosamine] and BMI during a 3 years follow-up. Surface electrogastrography (EGG) was performed on 49 children with diabetes aged 10.3±4.4 (mean±SD) years and 17 age-matched healthy controls after fasting glucose, glycosylated haemoglobin, and fructosamine were measured. EGG parameters [percentage of bradygastria, 3 cycles per minute, tachygastria, dominant frequency instability coefficient, and power ratio] were analysed and compared with blood analysis. Patients with diabetes exhibited an increase in preprandial bradygastria 7.9±8.8 cpm (mean±SD) compared with controls 2.1±1.0 (P=0.011), with an associated decrease in preprandial normogastria (72.2±14.5 vs. 82.7±14.7; P=0.013). Normogastric power ratio (postprandial/ preprandial power) was significantly increased in the children with diabetes compared with controls (mean: 6.67 vs. 3.14, P=0.034). A longer duration of diabetes was associated with an increased risk of EGG abnormalities (P=0.036). Marked hyperglycaemia at the time of study was associated with postprandial bradygastria (P=0.01) and power ratio bradygastria (P=0.042). Changes in glycosylated haemoglobin, fructosamine and BMI did not affect EGG parameters. EGG abnormalities, presented early in a high proportion of diabetic children, are related to the acute hyperglycaemia. These abnormalities are not consistently present in the follow-up studies and not related to the glycosylated haemoglobin and fructosamine. Diabetic autonomic neuropathy is therefore an unlikely pathogenic factor for EGG abnormalities in children with diabetes.

  20. The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells.

    Science.gov (United States)

    Sun, Shuqin; Yang, Shuo; Dai, Min; Jia, Xiujuan; Wang, Qiyan; Zhang, Zheng; Mao, Yongjun

    2017-06-13

    Apoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC). Astragalus polysaccharides (APS), an extract of astragalus membranaceus (AM), is an effective cardioprotectant. Currently, little is known about the detailed mechanisms underlying cardioprotective effects of APS. The aims of this study were to investigate the potential effects and mechanisms of APS on apoptosis employing a model of high glucose induction of apoptosis in H9C2 cells. A model of high glucose induction of H9C2 cell apoptosis was adopted in this research. The cell viabilities were analyzed by MTT assay, and the apoptotic response was quantified by flow cytometry. The expression levels of the apoptosis related proteins were determined by Real-time PCR and western blotting. Incubation of H9C2 cells with various concentrations of glucose (i.e., 5.5, 12.5, 25, 33 and 44 mmol/L) for 24 h revealed that cell viability was reduced by high glucose dose-dependently. Pretreatment of cells with APS could inhibit high glucose-induced H9C2 cell apoptosis by decreasing the expressions of caspases and the release of cytochrome C from mitochondria to cytoplasm. Further experiments also showed that APS could modulate the ratio of Bcl-2 to Bax in mitochondria. APS decreases high glucose-induced H9C2 cell apoptosis by inhibiting the expression of pro-apoptotic proteins of both the extrinsic and intrinsic pathways and modulating the ratio of Bcl-2 to Bax in mitochondria.

  1. Early diagnosis of retinopathy in juvenile diabetes by fluorescence angiography

    International Nuclear Information System (INIS)

    Krzywicki, S.; Slankiewicz, A.; Jablonska-Budaj, U.

    1980-01-01

    The authors defined the usefulness of the fluorescein angiography of the retina and choroid in the early stage diagnosis of diabetic retinopathy in children comparing its results to the traditional ophthalmoscopy. Examination involved 50 children from 4 to 18 (30 boys and 20 girls) on insulin treatment. The duration of the disease was 1 to 14 years (average 7.36 years). Ophthalmoscopy showed pathological changes in 24% of the children. The fluorescein angiography visualized more microaneurysms compared to ophthalmoscopy and showed them sometimes in the eyes where they had not been found in eye fundus studies. By means of angiography the early and advanced stages of vascular complications were found in 64% of patients. Comparing to ophthalmoscopy a 40% increase was noted. Fluorescein angiography can lead to the decrease in the number of patients with markedly impaired visual acuity and cases of blindness in the diabetic population. (author)

  2. Early diagnosis of retinopathy in juvenile diabetes by fluorescence angiography

    Energy Technology Data Exchange (ETDEWEB)

    Krzywicki, S; Slankiewicz, A; Jablonska-Budaj, U [Szpital-Pomnik Centrum Zdrowia Dziecka, Warsaw (Poland). Zespol Problemowy Okulistiky

    1980-09-01

    The authors defined the usefulness of the fluorescein angiography of the retina and choroid in the early stage diagnosis of diabetic retinopathy in children comparing its results to the traditional ophthalmoscopy. Examination involved 50 children from 4 to 18 (30 boys and 20 girls) on insulin treatment. The duration of the disease was 1 to 14 years (average 7.36 years). Ophthalmoscopy showed pathological changes in 24% of the children. The fluorescein angiography visualized more microaneurysms compared to ophthalmoscopy and showed them sometimes in the eyes where they had not been found in eye fundus studies. By means of angiography the early and advanced stages of vascular complications were found in 64% of patients. Comparing to ophthalmoscopy a 40% increase was noted. Fluorescein angiography can lead to the decrease in the number of patients with markedly impaired visual acuity and cases of blindness in the diabetic population.

  3. Vector flow mapping in obstructive hypertrophic cardiomyopathy to assess the relationship of early systolic left ventricular flow and the mitral valve.

    Science.gov (United States)

    Ro, Richard; Halpern, Dan; Sahn, David J; Homel, Peter; Arabadjian, Milla; Lopresto, Charles; Sherrid, Mark V

    2014-11-11

    The hydrodynamic cause of systolic anterior motion of the mitral valve (SAM) is unresolved. This study hypothesized that echocardiographic vector flow mapping, a new echocardiographic technique, would provide insights into the cause of early SAM in obstructive hypertrophic cardiomyopathy (HCM). We analyzed the spatial relationship of left ventricular (LV) flow and the mitral valve leaflets (MVL) on 3-chamber vector flow mapping frames, and performed mitral valve measurements on 2-dimensional frames in patients with obstructive and nonobstructive HCM and in normal patients. We compared 82 patients (22 obstructive HCM, 23 nonobstructive HCM, and 37 normal) by measuring 164 LV pre- and post-SAM velocity vector flow maps, 82 maximum isovolumic vortices, and 328 2-dimensional frames. We observed color flow and velocity vector flow posterior to the MVL impacting them in the early systolic frames of 95% of obstructive HCM, 22% of nonobstructive HCM, and 11% of normal patients (p 60° of local vector flow onto the posterior surface of the leaflets whether the flow was ejection (59%) or the early systolic isovolumic vortex (41%). Ricochet of vector flow, rebounding off the leaflet into the cul-de-sac, was noted in 82% of the obstructed HCM, 9% of nonobstructive HCM, and none (0%) of the control patients (p Flow velocities in the LV outflow tract on the pre-SAM frame 1 and 2 mm from the tip of the anterior leaflet were low: 39 and 43 cm/s, respectively. Early systolic flow impacts the posterior surfaces of protruding MVL initiating SAM in obstructive HCM. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  4. The early use of insulin in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    PHILIP LEVY

    2004-06-01

    Full Text Available 60?70% of all patients with Type 2 Diabetes Mellitus will ultimately require insulin therapy for the management of their diabetes. Irisulin may be used alone, or in combination with oral agents. The early use of insulin can be very important in decreasing the incidence of micro-vascular complications and in helping to delay the onset of macro-vascular complications. The United Kingdom Prospective Diabetes Study and the Kumamoto Study have shown the beneficial effects of good glucose control in type 2 diabetes mellitus. The DECODE study has related overall mortality to the level of glucose control and specifically to the postprandial glucose. The American Association of Clinical Endocrinologists has established a goal of 6.5% or less for HgbAlc. The appropriate use of insulin will allow us to achieve this goal without causing the patient any undue harm. There are many barriers to insulin therapy including psychological barriers of both the patient and the doctor, and unrealistic fears of both insulin therapy and therapy with self-administered injections. These barriers will be discussed as well as methods to overcome them. Insulin therapy is beneficial and has no long term adverse effects. The incidence of severe hypoglycemia is extremely low in type 2 diabetes. Weight gain is minimal. Insulin therapy by reducing glucose toxicity may also increase the effectiveness of oral anti-hyperglycemic agents. The physician taking care of patients with diabetes should be aggressive and should have no fears of initiating insulin therapy. Insulin dosage is flexible and good control is possible in most patients. The most common use of insulin in type 2 diabetes is as an add-on to oral agents if control with oral agents alone is unsatisfactory. Frequently this involves the use of a single dose of intermediate or long acting insulin or an insulin mixture in the evening. If control is not attained with a single dose, then the patient can be placed on an insulin

  5. Association of choroidal thickness with early stages of diabetic retinopathy in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun; Shen; Xiu-Fen; Yang; Jun; Xu; Chong-Yang; She; Wen-Wen; Wei; Wan-Lu; Zhu; Ning-Pu; Liu

    2017-01-01

    AIM:To assess the correlation between choroidal thickness(CT) and the early stages of diabetic retinopathy(DR) in type 2 diabetic patients.METHODS:We divided 83 diabetic patients(51-80 years of age;50 females) into non diabetic retinopathy group(NDR) and mild/moderate nonproliferative diabetic retinopathy(NPDR) group,and compared them with 26 non-diabetic control subjects(51-78 years of age;16 females).Subfoveal choroidal thickness(SFCT) and parafoveal choroidal thickness(PFCT) were measured using enhanced depth imaging spectral-domain optical coherence tomography(EDI-OCT).Ocular health status,disease duration,body mass index,and hemoglobin A1c(Hb A1c) were recorded.RESULTS:The mean ages of the NDR,NPDR,and control groups were 68.0±6.9y,67.8±6.4y,and 65.1±6.3y,respectively(P=0.17).Pearson correlation of the right and left eyes for the control subjects was 0.95 and for the NDR subjects was 0.93.SFCT for the right eyes of the controls was 252.77± 41.10 μm,which was significantly thicker than that of the right eyes in NDR group(221.51±46.56 μm) and the worse eyes of the NPDR group(207.18±61.87 μm;ANOVA,P<0.01).In the diabetic patients pooled together,age was the only variable significantly associated with SFCT(multiple linear regression analysis,P=0.01).CONCLUSION:CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with the control eyes.Age is significantly associated with SFCT in the diabetic patients.Diabetic choroidopathy may be present before clinical retinopathy.

  6. Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

    Science.gov (United States)

    McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

    2015-01-01

    The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

  7. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  8. Well-Being and Diabetes Management in Early Pregnant Women with Type 1 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Karolina Linden

    2016-08-01

    Full Text Available This paper explores well-being and diabetes management in women with type 1 diabetes mellitus (DM in early pregnancy and investigates associations among perceived well-being, diabetes management, and maternal characteristics. Questionnaires were answered by 168 Swedish women. Correlation analyses were conducted with Spearman’s correlation coefficient (rs. The women reported relatively high scores of self-efficacy in diabetes management (SWE-DES-10: 3.91 (0.51 and self-perceived health (excellent (6.5%, very good (42.3%, good (38.7%, fair (11.3% and poor (1.2%. Moderate scores were reported for general well-being (WBQ-12: 22.6 (5.7 and sense of coherence (SOC-13: 68.9 (9.7, moderate/low scores for hypoglycemia fear (SWE-HFS 26.6 (11.8 and low scores of diabetes-distress (SWE-PAID-20 27.1 (15.9. A higher capability of self-efficacy in diabetes management showed positive correlations with self-perceived health (rs = −0.41, p < 0.0001 and well-being (rs = 0.34, p < 0.0001 as well as negative correlations with diabetes distress (rs = −0.51, p < 0.0001 and hypoglycemia worries (rs = −0.27, p = 0.0009. Women with HbA1c levels of ≤48 mmL/mol scored higher in the subscales “goal achievement” in SWE-DES (p = 0.0028 and “comprehensibility” in SOC (p = 0.016. Well-being and diabetes management could be supported by strengthening the women’s capability to achieve glycemic goals and their comprehensibility in relation to the treatment. Further studies are needed to test this.

  9. EXTERNAL VALIDATION OF THE DIABETES EARLY READMISSION RISK INDICATOR (DERRI™).

    Science.gov (United States)

    Rubin, Daniel J; Recco, Dominic; Turchin, Alexander; Zhao, Huaqing; Golden, Sherita Hill

    2018-04-06

    The Diabetes Early Readmission Risk Indicator (DERRI ™ ) was previously developed and internally validated as a tool to predict the risk of all-cause readmission within 30 days of discharge (30-d readmission) of hospitalized patients with diabetes. In this study, the predictive performance of the DERRI ™ with and without additional predictors was assessed in an external sample. We conducted a retrospective cohort study of adult patients with diabetes discharged from 2 academic medical centers between 1/1/2000 and 12/31/2014. We applied the previously developed DERRI ™ , which includes admission laboratory results, sociodemographics, a diagnosis of certain comorbidities, and recent discharge information, and evaluated the effect of adding metabolic indicators on predictive performance using multivariable logistic regression. Total cholesterol and A1c were selected based on clinical relevance and univariate association with 30-d readmission. Among 105,974 discharges, 19,032 (18.0%) were followed by 30-d readmission for any cause. The DERRI ™ had a C-statistic of 0.634 for 30-d readmission. Total cholesterol (TC) was the lipid parameter most strongly associated with 30-d readmission. The DERRI ™ predictors, A1c, and TC were significantly associated with 30-d readmission; however, their addition to the DERRI ™ did not significantly change model performance (C-statistic 0.643 [95% CI, 0.638-0.647], p=0.92). Performance of the DERRI ™ in this external cohort was modest but comparable to other readmission prediction models. Addition of A1c and TC to the DERRI ™ did not significantly improve performance. Although the DERRI ™ may be useful to direct resources toward diabetes patients at higher risk, better prediction is needed. DERRI = Diabetes Early Readmission Risk Indicator; TC = Total cholesterol; A1c = hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; DKA = diabetic ketoacidosis; HHS

  10. Vascular Changes and Neurodegeneration in the Early Stages of Diabetic Retinopathy

    DEFF Research Database (Denmark)

    Jonsson, Karoline Boegeberg; Frydkjaer-Olsen, Ulrik; Grauslund, Jakob

    2016-01-01

    INTRODUCTION: Neurodegeneration is an early component of diabetic retinopathy (DR). It is unclear whether neurodegeneration is an independent factor or a consequence of damaged retinal vasculature. The aims of this study were to review the literature concerning neurodegeneration in diabetic...

  11. Lone ventricular cardiomyopathy,

    African Journals Online (AJOL)

    ... (I) cardiac catheterisation, including coronary arteriography and pulmonary ... described existence of lone ventricular idiopathic ... spectrum of classic idiopathic dilated cardiomyopathy. ... endomyocardial fibrosis, and from discussions at an.

  12. Early feeding and neonatal hypoglycemia in infants of diabetic mothers

    Directory of Open Access Journals (Sweden)

    Leandro Cordero

    2013-12-01

    Full Text Available Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30% had hypoglycemia, corrected by early feeding in 75 (86%, while 12 (14% required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%, prematurity (33% or prevention of hypoglycemia (27%. Although all newborn intensive care unit patients received intravenous dextrose, 22 (22% had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82% were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding.

  13. Early feeding and neonatal hypoglycemia in infants of diabetic mothers

    Science.gov (United States)

    Ramesh, Shilpa; Hillier, Kirsty; Giannone, Peter J; Nankervis, Craig A

    2013-01-01

    Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL) were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30%) had hypoglycemia, corrected by early feeding in 75 (86%), while 12 (14%) required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%), prematurity (33%) or prevention of hypoglycemia (27%). Although all newborn intensive care unit patients received intravenous dextrose, 22 (22%) had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82%) were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding. PMID:26770697

  14. Magnetic resonance imaging in familial hypertrophic cardiomyopathy associated with abnormal thallium perfusion and cardiac enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Nagata, Seiki; Sakakibara, Hiroshi

    1988-05-01

    Gated magnetic resonance imaging (MRI) was performed in 6 patients with familial hypertrophic cardiomyopathy associated with abnormal thallium perfusion, and 12 patients with ordinary hypertrophic cardiomyopathy. The patients with ordinary hypertrophic cardiomyopathy and abnormal thickening of the septal wall and normal left ventricular dimensions, while the patients with familial hypertrophic cardiomyopathy had focal wall thinning (usually involving the apical-septal wall) and dilated left ventricle in addition to hypertrophied heart. The quantitative measurement for cardiac dimensions using MRI was similar to that found on echocardiography in all cases. In addition, inhomogeneous signal intensities at left ventricular wall were observed in 3 cases of familial hypertrophic cardiomyopathy, which may suggest the existence of myocardial fibrosis. Gated MRI should be performed for early detection and follow-up of hypertrophic cardiomyopathy, since some patients will progress from hypertrophic cardiomyopathy to dilated cardiomyopathy.

  15. Early Life Factors and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Xinli Jiang

    2013-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity, behavior (smoking, drinking, and junk food diet, hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors.

  16. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    Science.gov (United States)

    ... cardiomyopathy Merck Manual Consumer Version: Cardiomyopathy Merck Manual Consumer Version: Overview of Abnormal Heart Rhythms Orphanet: Arrhythmogenic right ventricular cardiomyopathy Orphanet: Familial isolated arrhythmogenic right ventricular ...

  17. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alejandra Guillermina Miranda-Díaz

    2016-01-01

    Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

  18. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    Science.gov (United States)

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  19. Dynamic electrocardiographic changes in patients with arrhythmogenic right ventricular cardiomyopathy.

    LENUS (Irish Health Repository)

    Quarta, Giovanni

    2010-04-01

    Electrocardiographic (ECG) abnormalities of depolarisation and repolarisation contribute to the diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC). The development of diagnostic ECG features were investigated in a genotyped cohort with ARVC to provide more sensitive markers of early disease.

  20. Proliferative diabetic retinopathy after vitrectomy early factors affect IOP

    Directory of Open Access Journals (Sweden)

    Shi-Bo Liu

    2013-05-01

    Full Text Available AIM:To explore possible causes of early postoperative elevated intraocular pressure caused by proliferative diabetic retinopathy(PDRvitrectomy. METHODS:Totally 72 cases(100 eyeswhich have performed vitrectomy for proliferative diabetic retinopathy were retrospectively analyzed to observe the incidence of postoperative ocular hypertension, and the relevant factors that caused postoperative high intraocular pressure were statistically analyzed. Early postoperative ocular hypertension diagnostic criteria: any time after 2 weeks of non-contact tonometer measured IOP> 25mmHg(1mmHg=0.133kPa. RESULTS:High intraocular pressure after vitrectomy occurred in 27 eyes(27%, the incidence of male and female were 27.27%, 26.79%, the difference was not statistically significant(P>0.05. Eyes filled with balanced liquid filling incidence rate of 30.95%, 6.25%, and the difference was statistically significant(P0.05. Incidences of intraoperative panretinal photocoagulation and additional retinal photocoagulation group were 41%, 20%, and the difference was statistically significant(P<0.05. Preoperative retinopathy of four, five, six groups of incidence were 9.52%, 23.81%, 40.56%, and the groups were statistically significant(P<0.05. Unconsolidated preoperative retinal detachment and retinal detachment incidence rate of 19%, 41%, and the difference was statistically significant(P<0.05. Surgery in the united lens resection with intraoperative unfederated lens the resection group's incidence rate of 34%, 15%, the difference was statistically significant(P<0.05. Logistic regression analysis showed that retinal detachment preoperative and intraoperative intraocular filling were independent risk factors that caused early postoperative ocular hypertension after vitrectomy. CONCLUSION:Post-operative ocular hypertension after PDR vitrectomy is related to preoperative retinal detachment, intraoperative lensectomy, intraoperative intraocular filling, and intraoperative

  1. Plasma bradykinin and early diabetic nephropathy lesions in type 1 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Kevin M Wheelock

    preservation of glomerular structures, suggesting that elevations of these kinin concentrations may reflect adaptive responses to early renal structural changes in diabetic nephropathy.

  2. Potential role of immunoablation and hematopoietic cell transplantation in the treatment of early diabetes type 1.

    Science.gov (United States)

    Snarski, Emilian; Milczarczyk, Alicja; Franek, Edward; Jedrzejczak, Wieslaw

    2010-01-01

    Immunoablation with autologous hematopoietic cell transplantation has shown some effectiveness in the treatment of autoimmune diseases as diverse as aplastic anemia, systemic lupus erythematosus, multiple sclerosis and Crohn's disease. It has been recently shown that this treatment might prevent or delay development of diabetes type 1. The majority of more than 30 patients with early diabetes type 1 who underwent immunoablation and hematopoietic cell transplantation in various centers in the world achieved durable remission of diabetes and independence of exogenous insulin. This review summarizes advantages and risks of this treatment of early diabetes type 1.

  3. Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

    Science.gov (United States)

    Calcagni, Giulio; Adorisio, Rachele; Martinelli, Simone; Grutter, Giorgia; Baban, Anwar; Versacci, Paolo; Digilio, Maria Cristina; Drago, Fabrizio; Gelb, Bruce D; Tartaglia, Marco; Marino, Bruno

    2018-04-01

    RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Early diagnostics and incidence of diabetic nephropathy depending on type 1 diabetes mellitus duration

    Directory of Open Access Journals (Sweden)

    V.A. Maslianko

    2017-03-01

    Full Text Available The objective — to establish the incidence of diabetic nephropathy (DN depending on duration of type 1 diabetes mellitus (DM, and also the content of cystatin С as a marker of early kidney damage. Materials and methods. Twenty eight patients with type 1 DM were enrolled in prospective study (11 men and 17 women aged 34.8 ± 7.2 years. Clinical and functional examination included the standard evaluation of renal function, and also the study of serum level of cystatin С. Results. In 17 out of 28 patients, the indexes of glomerular filtration rate calculated using the formulas of CKD-ЕРIcreat and CKD-ЕРIcys, indicated the different stages of chronic kidneys disease. Conclusions. Determination of cystatin C level and calculation of glomerular filtration rate using this index allows diagnosing the preclinical stages of kidney dysfunction in patients with type 1 DM in the normal creatinine level in the blood and without decline in glomerular filtration rate calculated using creatinine value. According to a retrospective study, the incidence and severity of DN in patients with type 1 DM increases with disease duration of more than 10 years.

  5. Glucose intolerance in early postpartum in women with gestational diabetes: Who is at increased risk?

    Science.gov (United States)

    Leuridan, Liesbeth; Wens, Johan; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal; Benhalima, Katrien

    2015-08-01

    Women with a history of gestational diabetes (GDM) have an increased risk for developing type 2 diabetes in the years after the index pregnancy. Some women with GDM already develop glucose intolerance in early postpartum. The best screening strategy for glucose intolerance in early postpartum among women with a history of GDM is still debated. We review the most important risk factors of women with GDM to develop glucose intolerance within one year postpartum. We also discuss the current recommendations for screening in early postpartum and the many challenges to organize postpartum follow up in primary care. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  6. Takotsubo cardiomyopathy following subarachnoid hemorrhage

    International Nuclear Information System (INIS)

    Wajnberg, Eduardo

    2012-01-01

    Takotsubo cardiomyopathy corresponds to a syndrome characterized by a transient myocardial dysfunction affecting the left ventricular apex that classically occurs after major physical or emotional stress (also called 'broken heart syndrome' or 'stress-induced cardiomyopathy'). The author describes the case of a patient with takotsubo cardiomyopathy induced by subarachnoid hemorrhage. (author)

  7. Inhibition of the adrenomedullin/nitric oxide signaling pathway in early diabetic retinopathy.

    Science.gov (United States)

    Blom, Jan J; Giove, Thomas J; Favazza, Tara L; Akula, James D; Eldred, William D

    2011-06-01

    The nitric oxide (NO) signaling pathway is integrally involved in visual processing and changes in the NO pathway are measurable in eyes of diabetic patients. The small peptide adrenomedullin (ADM) can activate a signaling pathway to increase the enzyme activity of neuronal nitric oxide synthase (nNOS). ADM levels are elevated in eyes of diabetic patients and therefore, ADM may play a role in the pathology of diabetic retinopathy. The goal of this research was to test the effects of inhibiting the ADM/NO signaling pathway in early diabetic retinopathy. Inhibition of this pathway decreased NO production in high-glucose retinal cultures. Treating diabetic mice with the PKC β inhibitor ruboxistaurin for 5 weeks lowered ADM mRNA levels and ADM-like immunoreactivity and preserved retinal function as assessed by electroretinography. The results of this study indicate that inhibiting the ADM/NO signaling pathway prevents neuronal pathology and functional losses in early diabetic retinopathy.

  8. Direct diabetes-related costs in young patients with early-onset, long-lasting type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Christina Bächle

    Full Text Available OBJECTIVE: To estimate diabetes-related direct health care costs in pediatric patients with early-onset type 1 diabetes of long duration in Germany. RESEARCH DESIGN AND METHODS: Data of a population-based cohort of 1,473 subjects with type 1 diabetes onset at 0-4 years of age within the years 1993-1999 were included (mean age 13.9 (SD 2.2 years, mean diabetes duration 10.9 (SD 1.9 years, as of 31.12.2007. Diabetes-related health care services utilized in 2007 were derived from a nationwide prospective documentation system (DPV. Health care utilization was valued in monetary terms based on inpatient and outpatient medical fees and retail prices (perspective of statutory health insurance. Multiple regression models were applied to assess associations between direct diabetes-related health care costs per patient-year and demographic and clinical predictors. RESULTS: Mean direct diabetes-related health care costs per patient-year were €3,745 (inter-quartile range: 1,943-4,881. Costs for glucose self-monitoring were the main cost category (28.5%, followed by costs for continuous subcutaneous insulin infusion (25.0%, diabetes-related hospitalizations (22.1% and insulin (18.4%. Female gender, pubertal age and poor glycemic control were associated with higher and migration background with lower total costs. CONCLUSIONS: Main cost categories in patients with on average 11 years of diabetes duration were costs for glucose self-monitoring, insulin pump therapy, hospitalization and insulin. Optimization of glycemic control in particular in pubertal age through intensified care with improved diabetes education and tailored insulin regimen, can contribute to the reduction of direct diabetes-related costs in this patient group.

  9. Cardiomyopathy induced by anthracycline

    International Nuclear Information System (INIS)

    Quiroz, Isabel; Espinoza, Gerson; Poveda, Maria; Flores, Walter

    2002-01-01

    Anthracycline cardiomyopathy is less frequently encountered nowadays, due to the well recognized dose limitations and cardiac monitoring protocols used by chemotherapy centers. However, it is a condition that will persist due to the sensitivity of some patients to these drugs and the necessity for large doses to be used for certain individuals. We have demonstrated the benefit of angiotensin converting enzyme inhibitor therapy and would consider introducing these compounds at the earliest opportunity. The use of probucol and vitamins as antioxidants capable of preventing the onset of cardiomyopathy in humans appears to require further investigation but may significantly reduce the incidence of this condition in the future. (The author)

  10. Alterations to Bone Mineral Composition as an Early Indication of Osteomyelitis in the Diabetic Foot

    OpenAIRE

    Esmonde-White, Karen A.; Esmonde-White, Francis W.L.; Holmes, Crystal M.; Morris, Michael D.; Roessler, Blake J.

    2013-01-01

    OBJECTIVE Osteomyelitis in the diabetic foot is a major risk factor for amputation, but there is a limited understanding of early-stage infection, impeding limb-preserving diagnoses. We hypothesized that bone composition measurements provide insight into the early pathophysiology of diabetic osteomyelitis. RESEARCH DESIGN AND METHODS Compositional analysis by Raman spectroscopy was performed on bone specimens from patients with a clinical diagnosis of osteomyelitis in the foot requiring surgi...

  11. BAG3 myofibrillar myopathy presenting with cardiomyopathy.

    Science.gov (United States)

    Konersman, Chamindra G; Bordini, Brett J; Scharer, Gunter; Lawlor, Michael W; Zangwill, Steven; Southern, James F; Amos, Louella; Geddes, Gabrielle C; Kliegman, Robert; Collins, Michael P

    2015-05-01

    Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Choroidal thickness alterations in diabetic nephropathy patients with early or no diabetic retinopathy.

    Science.gov (United States)

    Kocasarac, Can; Yigit, Yavuz; Sengul, Erkan; Sakalar, Yildirim Beyazit

    2018-04-01

    To assess changes in choroidal thickness (CT) in diabetes patients with and without diabetic nephropathy using enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT). Thirty-five type 2 diabetes patients with a diagnosis of diabetic nephropathy (DNP) in nephrology department and 35 type 2 diabetes patients without nephropathy (non-DNP) were included in our prospective study consecutively. The control group comprised 34 healthy individuals. CT measurements were recorded under the fovea and at 1500 µm from the foveal center in the nasal and temporal sides. The study parameters also included age, refractive error, axial length, intraocular pressure, HbA1c, glomerular filtration rate and proteinuria amount. The subfoveal, temporal and nasal choroidal thickness was noted to be thinner in patients with DNP compared with non-DNP and normal subjects (p diabetic patients when diabetic nephropathy accompanies diabetes mellitus.

  13. Terahertz imaging for early screening of diabetic foot syndrome: A proof of concept

    Science.gov (United States)

    Hernandez-Cardoso, G. G.; Rojas-Landeros, S. C.; Alfaro-Gomez, M.; Hernandez-Serrano, A. I.; Salas-Gutierrez, I.; Lemus-Bedolla, E.; Castillo-Guzman, A. R.; Lopez-Lemus, H. L.; Castro-Camus, E.

    2017-02-01

    Most people with diabetes suffer some deterioration of the feet. Diabetic foot syndrome causes ulceration in about 15% of cases and such deterioration leads to amputation in about 2.5% of diabetic patients, diminishing their quality of life and generating extraordinary costs for patients and public health systems. Currently, there is no objective method for the detection of diabetic foot syndrome in its early stages. We propose terahertz imaging as a method for the evaluation of such deterioration. This screening method could aid the prevention and medical treatment of this condition in the future.

  14. Renal radioisotope clearance in an unselected group of diabetics - a tool for the early recognition of diabetic nephropathy

    International Nuclear Information System (INIS)

    Doschek, D.; Wulf, R.; Krause, F.J.; Kreiskrankenhaus Albstadt

    1980-01-01

    Our study in unselected patients with diabetes was undertaken to determine the relation between glomerular filtration rate (GFR) and renal plasma flow (RPF) according to the patient's age. The diagnostic work-up was done with patients in unselected disease states because a classification of all systemic manifestations of the diabetes was not possible. The lack of selection may therefore reduce the value of our statistical results. From age 55 onwards, there was a reduction in GFR and, to a lesser extent, in PRF esceeding that which was age-dependent. It is, therefore, recommended to check the clearance in all patients with diabetes older than 55 years. The clearance with radioisotopically labeled substances, being a very sensitive method for the evaluation of restricted renal function, may permit an early recognition of diabetic nephropathy. (orig.) [de

  15. Diagnostic value of determination of amount of urinary excretion of proteins for early diabetic nephropathy

    International Nuclear Information System (INIS)

    Li Zhuocheng; Chen Jianxiong; Yan Dewen

    2007-01-01

    Objective: To investigate the value of detection of changes of the amount of usinary excretion of albumin, β 2 -m, Tamm- Horsfall protein and α 1 -m for diagnosis of early diabetic nephropathy. Methods: The amounts of 24h urinary excretion of albumin, β 2 -m, Tamm-Horsfall protein and α 1 -m were determined with RIA in 78 patients with diabetes mellitus and 40 controls. Results: The amounts of 24h urinary excretion of albumin, β 2 -m, α 1 -m in patients with diabetes mellitus were significantly higher than those in controls (P<0.01 ), while the amount of Tamm-Horsfall protein was significantly lower (P<0.01). Among the diabetic patients, the changes of the amount of protein excretion were more pronounced in those with advanced impairment of renal function. Conclusion: Determination of amount of urinary excretion of proteins was helpful for diagnosis and assessment of early diabetic nephropathy. (authors)

  16. An automated approach for early detection of diabetic retinopathy using SD-OCT images.

    Science.gov (United States)

    ElTanboly, Ahmed H; Palacio, Agustina; Shalaby, Ahmed M; Switala, Andrew E; Helmy, Omar; Schaal, Shlomit; El-Baz, Ayman

    2018-01-01

      This study was to demonstrate the feasibility of an automatic approach for early detection of diabetic retinopathy (DR) from SD-OCT images. These scans were prospectively collected from 200 subjects through the fovea then were automatically segmented, into 12 layers. Each layer was characterized by its thickness, tortuosity, and normalized reflectivity. 26 diabetic patients, without DR changes visible by funduscopic examination, were matched with 26 controls, according to age and sex, for purposes of statistical analysis using mixed effects ANOVA. The INL was narrower in diabetes (p = 0.14), while the NFL (p = 0.04) and IZ (p = 0.34) were thicker. Tortuosity of layers NFL through the OPL was greater in diabetes (all p diabetes. In turn, carries the promise to a reliable non-invasive diagnostic tool for early detection of DR.

  17. Cardiomyopathy Following Latrodectus Envenomation

    Directory of Open Access Journals (Sweden)

    Levine, Michael

    2010-12-01

    Full Text Available Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22- year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy. [West J Emerg Med. 2010; 11(5:521-523.

  18. Hypertrophic Cardiomyopathy Association

    Science.gov (United States)

    ... be donated to Hypertrophic Cardiomyopathy Association. iGive.com - Online Shopping Joing iGive.com to earn money for the ... it works, check out the iGive website . AmazonSmile - Online Shopping Amazon donates 0.5% of the purchase price ...

  19. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  20. Application of serum TGF-β1 determination for early diagnosis of diabetic nephropathy

    International Nuclear Information System (INIS)

    Jiang Zhonglin; Jiang Guoliang

    2005-01-01

    Objective: To investigate the feasibility of obtaining early diagnosis of diabetic nephropathy (DN) with determination of serum transforming growth factor-β 1 (TGF- β 1 ). Methods: Serum TGF-β 1 (with ELISA) and β 2 -microglobulin (β 2 -m, with RIA) levels as well as urinany β 2 -m, albumin and mciro-amount of proteins were determined in 35 controls and 84 diabetic patients with different degrees of albuminuria (Group A: urinary albumin excretion UAE 300mg/24h, n=28). Results: The serum TGF-β 1 , β 2 -m and urinary β 2 -m contents were correlated well with UAE in the diabetic patients. Conclusion: TGF-β 1 and β 2 -m were sensitive markers for early renal function injury in diabetic patients and determination of serum TGF-β 1 levels was clinically useful for diagnosis of early DN. (authors)

  1. Early detection of left ventricular dysfunction in asymptomatic diabetic patient using strain and strain rate echocardiographic imaging

    Directory of Open Access Journals (Sweden)

    Rania Gaber

    2014-03-01

    Conclusion: Type 2 diabetes mellitus deteriorate both LV systolic and diastolic performance. Strain and strain rate by tissue Doppler Imaging is superior to conventional Doppler in early detection and evaluation of systolic and diastolic dysfunction in type 2 diabetic patients.

  2. Comparison between Early Treatment Diabetic Retinopathy Study 7-field retinal photos and non-mydriatic, mydriatic and mydriatic steered widefield scanning laser ophthalmoscopy for assessment of diabetic retinopathy

    DEFF Research Database (Denmark)

    Rasmussen, Malin L; Broe, Rebecca; Frydkjaer-Olsen, Ulrik

    2015-01-01

    AIMS: To compare non-mydriatic, mydriatic and steered mydriatic widefield retinal images with mydriatic 7-field Early Treatment Diabetic Retinopathy Study (ETDRS)-standards in grading diabetic retinopathy (DR). METHODS: We examined 95 patients (190 eyes) with type 1 diabetes. A non...

  3. Verification of multimarkers for detection of early stage diabetic retinopathy using multiple reaction monitoring.

    Science.gov (United States)

    Kim, Kyunggon; Kim, Sang Jin; Han, Dohyun; Jin, Jonghwa; Yu, Jiyoung; Park, Kyong Soo; Yu, Hyeong Gon; Kim, Youngsoo

    2013-03-01

    Diabetic retinopathy (DR) is a complication of diabetes and 80% of diabetes mellitus (DM) patients whose DM duration is over 10 years can be expected to suffer with DR. The diagnosis of DR depends on an ophthalmological examination, and no molecular methods of screening DR status exist. Nonproliferative diabetic retinopathy (NPDR) is the early DR which is hard to be noticed in early NPDR, showing significant cause of adult blindness in type 2 diabetes patients. Protein biomarkers have been valuable in the diagnosis of disease and the use of multiple biomarkers has been suggested to overcome the low specificity of single ones. For biomarker development, multiple reaction monitoring (MRM) has been spotlighted as an alternative method to quantify target proteins with no need for immunoassay. In this study, 54 candidate DR marker proteins from a previous study were verified by MRM in plasma samples from NPDR patients in 3 stages (mild, moderate and severe; 15 cases each) and diabetic patients without retinopathy (15 cases) as a control. Notably, 27 candidate markers distinguished moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, generating AUC values (>0.7). Specifically, 28 candidate proteins underwent changes in expression as type 2 diabetic patients with no diabetic retinopathy progressed to mild and moderate NPDR. Further, a combination of 4 markers from these 28 candidates had the improved specificity in distinguishing moderate NPDR from type 2 diabetic patients with no diabetic retinopathy, yielding a merged AUC value of nearly 1.0. We concluded that MRM is a fast, robust approach of multimarker panel determination and an assay platform that provides improved specificity compared with single biomarker assay systems.

  4. The Relationship between Peripheral Nerve Conduction Velocity and Ophthalmological Findings in Type 2 Diabetes Patients with Early Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Azusa Ito

    2018-01-01

    Full Text Available Purpose. Nerve conduction velocity (NCV is an indicator of neuronal damage in the distal segment of the peripheral nerves. Here, we determined the association between NCV and other systemic and ocular clinical findings, in type 2 diabetes patients with early diabetic retinopathy (DR. Methods. This study included 42 eyes of 42 type 2 diabetes patients (median age: 54 years with no DR or with mild nonproliferative DR. Standard statistical techniques were used to determine associations between clinical findings. Results. Sural sensory conduction velocity (SCV and tibial motor conduction velocity (MCV were significantly lower in mild nonproliferative DR patients than patients with no DR (P=0.008 and P=0.01, resp.. Furthermore, logistic regression analyses revealed that sural SCV and tibial MCV were independent factors contributing to the presence of mild nonproliferative DR (OR 0.83, P=0.012 and OR 0.69 P=0.02, resp.. Tibial MCV was correlated with choroidal thickness (CT (P=0.01, and a multiple regression analysis revealed that age, tibial MCV, and carotid intima-media thickness were independent associating factors with CT (P=0.035, P=0.015, and P=0.008, resp.. Conclusions. Our findings suggest that reduced NCV may be closely associated with early DR in type 2 diabetes patients. Thus, reduced nerve conduction is a potential early biomarker of DR.

  5. Early onset diabetes-genetic and hormonal analysis in pakistan population

    International Nuclear Information System (INIS)

    Wahid, M.; Kamran, M.

    2016-01-01

    Background: Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Methods: Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Results: Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. Conclusion: relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population. (author)

  6. Takotsubo (Stress Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Justin J Hourmozdi

    2017-01-01

    Full Text Available History of present illness: A 59-year-old male presented to the emergency department in shock from pneumonia. The patient was initially afebrile, pulse rate 120 beats per minute, blood pressure 117/69 mmHg, respiratory rate 42 breaths per minute, pulse oximetry 94% on a non-rebreather mask and a lactate of 14 mmol/L. He became progressively more hypotensive despite fluid resuscitation and was started on norepinephrine. Shortly after, the patient developed torsades de pointes that was terminated with intravenous push magnesium. His initial ECG had shown sinus tachycardia; however, repeat ECG showed ST-segment elevation in the inferolateral leads and the patient had troponin I elevation that peaked at 16 ng/mL. Significant findings: Bedside echocardiography showed the findings consistent with Takotsubo cardiomyopathy. Echocardiographic images are shown in subxiphoid (A and apical four chamber (B views. Note the apical ballooning appearance (asterisk of the left ventricle (LV. Discussion: Formal echocardiography confirmed features classic for Takotsubo (stress cardiomyopathy, including globally depressed left ventricle (LV ejection fraction, systolic apical ballooning appearance of the LV, mid and apical segments of LV depression, and hyper kinesis of the basal walls. Takotsubo cardiomyopathy is a syndrome known to cause ST-segment elevation on ECG, transient LV dysfunction, and dysrhythmia in the absence of acute obstructive coronary disease. There is no consensus on diagnostic criteria; however, these criteria are commonly used: 1 transient hypokinesis, akinesis, or dyskinesis in the LV mid-segments with or without apical involvement; regional wall motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger 2 the absence of acute coronary disease or angiographic evidence of acute plaque rupture 3 new ECG abnormalities (ST-segment elevation and/or T-wave inversion or modest

  7. Computational Intelligence in Early Diabetes Diagnosis: A Review

    Science.gov (United States)

    Shankaracharya; Odedra, Devang; Samanta, Subir; Vidyarthi, Ambarish S.

    2010-01-01

    The development of an effective diabetes diagnosis system by taking advantage of computational intelligence is regarded as a primary goal nowadays. Many approaches based on artificial network and machine learning algorithms have been developed and tested against diabetes datasets, which were mostly related to individuals of Pima Indian origin. Yet, despite high accuracies of up to 99% in predicting the correct diabetes diagnosis, none of these approaches have reached clinical application so far. One reason for this failure may be that diabetologists or clinical investigators are sparsely informed about, or trained in the use of, computational diagnosis tools. Therefore, this article aims at sketching out an outline of the wide range of options, recent developments, and potentials in machine learning algorithms as diabetes diagnosis tools. One focus is on supervised and unsupervised methods, which have made significant impacts in the detection and diagnosis of diabetes at primary and advanced stages. Particular attention is paid to algorithms that show promise in improving diabetes diagnosis. A key advance has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review presents and explains the most accurate algorithms, and discusses advantages and pitfalls of methodologies. This should provide a good resource for researchers from all backgrounds interested in computational intelligence-based diabetes diagnosis methods, and allows them to extend their knowledge into this kind of research. PMID:21713313

  8. Computational intelligence in early diabetes diagnosis: a review.

    Science.gov (United States)

    Shankaracharya; Odedra, Devang; Samanta, Subir; Vidyarthi, Ambarish S

    2010-01-01

    The development of an effective diabetes diagnosis system by taking advantage of computational intelligence is regarded as a primary goal nowadays. Many approaches based on artificial network and machine learning algorithms have been developed and tested against diabetes datasets, which were mostly related to individuals of Pima Indian origin. Yet, despite high accuracies of up to 99% in predicting the correct diabetes diagnosis, none of these approaches have reached clinical application so far. One reason for this failure may be that diabetologists or clinical investigators are sparsely informed about, or trained in the use of, computational diagnosis tools. Therefore, this article aims at sketching out an outline of the wide range of options, recent developments, and potentials in machine learning algorithms as diabetes diagnosis tools. One focus is on supervised and unsupervised methods, which have made significant impacts in the detection and diagnosis of diabetes at primary and advanced stages. Particular attention is paid to algorithms that show promise in improving diabetes diagnosis. A key advance has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review presents and explains the most accurate algorithms, and discusses advantages and pitfalls of methodologies. This should provide a good resource for researchers from all backgrounds interested in computational intelligence-based diabetes diagnosis methods, and allows them to extend their knowledge into this kind of research.

  9. Hypertrophic Cardiomyopathy: Clinical Update.

    Science.gov (United States)

    Geske, Jeffrey B; Ommen, Steve R; Gersh, Bernard J

    2018-05-01

    Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy in the absence of a secondary cause. The genetic underpinnings of HCM arise largely from mutations of sarcomeric proteins; however, the specific underlying mutation often remains undetermined. Patient presentation is phenotypically diverse, ranging from asymptomatic to heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in most patients. The goal of therapeutic interventions is largely to reduce dynamic obstruction, with treatment modalities spanning lifestyle modifications, pharmacotherapies, and septal reduction therapies. A small subset of patients with HCM will experience sudden cardiac death, and risk stratification remains a clinical challenge. This paper presents a clinical update for diagnosis, family screening, clinical imaging, risk stratification, and management of symptoms in patients with HCM. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Cardiovascular morbidity and early mortality cluster in parents of type 1 diabetic patients with diabetic nephropathy

    DEFF Research Database (Denmark)

    Tarnow, L; Rossing, P; Nielsen, F S

    2000-01-01

    OBJECTIVE: A familial predisposition was proposed to be a determinant of the increased morbidity and mortality from cardiovascular disease in type 1 diabetic patients with diabetic nephropathy. The insertion allele of an insertion/deletion polymorphism in the ACE (ACE/ID) gene seems to protect ag...

  11. Mental health in early pregnancy is associated with pregnancy outcome in women with pregestational diabetes

    DEFF Research Database (Denmark)

    Callesen, N F; Secher, A L; Cramon, P

    2015-01-01

    -related quality of life, anxiety, depression and locus of control were seen in women delivering large or appropriate for gestational age infants. CONCLUSIONS: Poor mental quality of life and the presence of depressive symptoms in early pregnancy were associated with preterm delivery in women with pregestational......AIM: To explore the role of early pregnancy health-related quality of life, anxiety, depression and locus of control for pregnancy outcome in women with pregestational diabetes. METHODS: This was a cohort study of 148 pregnant women with pregestational diabetes (118 with Type 1 diabetes and 30...... with Type 2 diabetes), who completed three internationally validated questionnaires: the 36-item Short-Form Health Survey, the Hospital Anxiety and Depression Scale and the Multidimensional Health Locus of Control survey at 8 weeks. Selected pregnancy outcomes were preterm delivery (

  12. MRI of the cardiomyopathies

    International Nuclear Information System (INIS)

    Di Cesare, Ernesto

    2001-01-01

    We examined the potentialities of Magnetic resonance imaging (MRI) in the evaluation of the main cardiomyopathies: hypertrophic, dilated, restrictive and arrhythmogenic right ventricular. The hypertrophic cardiomyopathy is generally adequately investigated by echocardiography, that well defines the myocardial thickening and the obstruction of the left ventricular output. However, by echocardiography we still have difficulties in the evaluation of the apex of the left ventricle and the right ventricle involvement. MRI provides a complete evaluation of the heart with a clear evidence also of the echocardiographic dark zones by means of a clear evidence of the apex of the right ventricle. The dilated form is also well investigated by MRI that provides a clear evaluation of the volumes, mass and ejection fraction by means of the 3D analysis including conditions of the ventricular remodelling. Moreover, this technique helps in the differential diagnosis of acute myocarditis. In the acute phase of myocarditis (first 2 weeks), in fact, the myocardium produces high signal intensity on the T2 weighted sequences due to the presence of oedema. The third form of cardiomyopathy is the restrictive one, characterised by reduced diastolic filling and diastolic volume, normality of the systolic function and parietal thickness, interstitial fibrosis and enlargement of both atria. The mean potentiality of MRI is related to the differential diagnosis with constrictive pericarditis. Only in the former, the pericardium appears irregularly thickened with areas exceeding 4 mm of pericardial thickness. Finally, the right ventricular arrhythmogenic cardiomyopathy represents the main indication to MRI evaluation. With this imaging modality we are can obtain a clear morpho-functional evaluation of the right ventricle and distinguish the intramyocardial adipose substitution characterised by areas of high signal in the myocardium

  13. Penile alterations at early stage of type 1 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Mingfang Tao

    Full Text Available ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.

  14. Histologic characterization of canine dilated cardiomyopathy.

    Science.gov (United States)

    Tidholm, A; Jönsson, L

    2005-01-01

    Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  16. Protective effect of turnip root ethanolic extract on early diabetic nephropathy in the rats

    Directory of Open Access Journals (Sweden)

    Bahram Amouoghli-Tabrizi

    2011-11-01

    Full Text Available Background: Diabetes mellitus is a metabolic disorder and one of its most important consequences is renal insufficiency. A multitude of herbs has been described for the treatment of diabetes mellitus. The aim of present study was to assess the protective effect of turnip root ethanolic extract (TREE on early nephropathy in alloxan-induced diabetic rats.Materials and Method: Eighty male Wistar rats were randomly allocated into 4 equal groups including: healthy rats, normal healthy rats receiving TREE, diabetic rats and diabetic rats receiving TREE. Diabetes was induced by a single injection of alloxan (120 mg/kg; i.p. The extract (200 mg/kg was gavaged to TREE treatment groups daily for 8 weeks. At the end of experiment; serum levels of urea, uric acid and creatinine were assessed. The lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS, and activities of superoxide dismutase, catalase and glutathione peroxidase were measured in the renal tissue. Finally, the biochemical findings were matched with histopathological verification. Statistically, the quantitative data obtained, compared among the groups by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p<0.05.Results: In the diabetic rats, TREE significantly decreased the levels of serum biomarkers of renal injury. Furthermore, TREE significantly decreased the lipid peroxidation and elevated the decreased levels of antioxidant enzymes in diabetic rats. Histopathological findings were in agreement with the biochemical findings.Conclusion: TREE has protective effect on early diabetic nephropathy in the rats with experimentally induced diabetes

  17. Peripartum cardiomyopathy as a part of familial dilated cardiomyopathy

    NARCIS (Netherlands)

    K.Y. van Spaendonck-Zwarts (Karin); J.P. van Tintelen (Peter); D.J. van Veldhuisen (Dirk); R. van der Werf (Rik); J.D.H. Jongbloed (Jan); W.J. Paulus (Walter); D. Dooijes (Dennis); M.P. van den Berg (Maarten)

    2010-01-01

    textabstractBACKGROUND-: Anecdotal cases of familial clustering of peripartum cardiomyopathy (PPCM) and familial occurrences of PPCM and idiopathic dilated cardiomyopathy (DCM) together have been observed, suggesting that genetic factors play a role in the pathogenesis of PPCM. We hypothesized that

  18. Early atherosclerosis and vascular inflammation in mice with diet-induced type 2 diabetes

    DEFF Research Database (Denmark)

    Bartels, E D; Bang, C A; Nielsen, L B

    2009-01-01

    and the median lesion area was 8.0 times higher than in fat-fed wild-type mice (P = 0.001). Intracellular adhesion molecule-1 staining of the aortic endothelium was most pronounced in the fat-fed apoB transgenic mice. CONCLUSIONS: Our findings suggest that diet-induced type 2 diabetes causes early......BACKGROUND: Obesity and type 2 diabetes increase the risk of atherosclerosis. It is unknown to what extent this reflects direct effects on the arterial wall or secondary effects of hyperlipidaemia. MATERIALS AND METHODS: The effect of obesity and type 2 diabetes on the development...

  19. Early insulin therapy in patients with type 2 diabetes mellitus ...

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (T2DM) is a progressive disease characterised by beta cell dysfunction and insulin resistance. Beta cell dysfunction progresses to beta cell failure. Many patients with T2DM are managed with oral agents until complications develop. 'Clinical inertia' in T2DM, defined as lack of initiation or ...

  20. Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Bjerregaard, Lise G; Jensen, Britt W; Ängquist, Lars

    2018-01-01

    Background Childhood overweight is associated with an increased risk of type 2 diabetes in adulthood. We investigated whether remission of overweight before early adulthood reduces this risk. Methods We conducted a study involving 62,565 Danish men whose weights and heights had been measured at 7...... and 13 years of age and in early adulthood (17 to 26 years of age). Overweight was defined in accordance with Centers for Disease Control and Prevention criteria. Data on type 2 diabetes status (at age ≥30 years, 6710 persons) were obtained from a national health registry. Results Overweight at 7 years.......14; 95% CI, 3.57 to 4.79). An increase in body-mass index between 7 years of age and early adulthood was associated with an increased risk of type 2 diabetes, even among men whose weight had been normal at 7 years of age. Conclusions Childhood overweight at 7 years of age was associated with increased...

  1. Urinary Glucose Screening for Early Detection of Asymptomatic Type 2 Diabetes in Jeonbuk Province Korean Schoolchildren.

    Science.gov (United States)

    Kim, Min Sun; Lee, Dae Yeol

    2017-06-01

    This study aimed to investigate the prevalence of glucosuria and the characteristics of diabetes in schoolchildren as detected by a school urine glucose screening program implemented from 2010 to 2013 in the Jeonbuk province area of Korea. A total of 110 children without known diabetes were analyzed. They were checked with an oral glucose tolerance test (OGTT) with other laboratory tests and their clinical data were collected. A total of 707,238 schoolchildren from a school population of 1,064,999 were screened for glucosuria. In total, over a 4-year period, 545 schoolchildren (0.077%) were positive for glucosuria on the second urine test. The prevalence of glucosuria was more common among middle and high schoolchildren than among elementary schoolchildren. Among 110 students who completed the OGTT to confirm diabetes, 40 were diagnosed with diabetes mellitus (DM); 39 children, type 2 diabetes mellitus (T2DM) and 1 child, slowly progressive insulin dependent diabetes mellitus (SPIDDM). The mean annual incidence of diabetes was 5.6 per 100,000 schoolchildren and adolescents. The subjects with diabetes diagnosed through the urine screening test showed minimal or no symptoms of diabetes. The students with diabetes were more likely to be woman and obese, and they have a higher body mass index, higher cholesterol, triglyceride, insulin, C-peptide, and fasting glucosuria values than the students with normal glucose tolerance. We identified 40 new cases of diabetes in the Korean schoolchildren with asymptomatic glucosuria on urine glucose screening. This finding shows that school urine glucose screening is a feasible and simple method for early detection of asymptomatic T2DM. © 2017 The Korean Academy of Medical Sciences.

  2. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    OpenAIRE

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P

  3. Cardiomyopathy in the pediatric patients

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2018-04-01

    Full Text Available Pediatric cardiomyopathies are a group of myocardial diseases with complex taxonomies. Cardiomyopathy can occur in children at any age, and it is a common cause of heart failure and heart transplantation in children. The incidence of pediatric cardiomyopathy is increasing with time. They may be associated with variable comorbidities, which are most often arrhythmia, heart failure, and sudden death. Medical imaging technologies, including echocardiography, cardiac magnetic resonance, and nuclear cardiology, are helpful in reaching a diagnosis of cardiomyopathy. Nevertheless, endomyocardial biopsy is the final diagnostic method of diagnosis. Patients warrant surgical operations, such as palliative operations, bridging operations, ventricular septal maneuvers, and heart transplantation, if pharmaceutical therapies are ineffective. Individual therapeutic regimens due to pediatric characteristics, genetic factors, and pathogenesis may improve the effects of treatment and patients' survival. Key Words: cardiomyopathy, classification, pediatrics

  4. Acute myocardial infarction and stress cardiomyopathy following the Christchurch earthquakes.

    Science.gov (United States)

    Chan, Christina; Elliott, John; Troughton, Richard; Frampton, Christopher; Smyth, David; Crozier, Ian; Bridgman, Paul

    2013-01-01

    Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36 am on 4 September 2010, magnitude 7.1 and at 12:51 pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region's only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations. Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others. There was a significant increase in overall admissions (pearthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6-6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44-2.62). Statistical analysis showed this to be a significant difference between the earthquakes (pearthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events.

  5. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2015-12-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  6. Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound

    Directory of Open Access Journals (Sweden)

    Saif Aasem

    2010-01-01

    Full Text Available To evaluate the role of renal duplex ultrasonography in the detection of early alte-ration of renal blood flow in type I diabetic patients, we studied with duplex ultrasound 32 patients with type I diabetes mellitus (19 males, 13 females, age range 8-19 years and 35 age and sex-matched controls. The resistivity indices (RIs and pulsatility indices (PIs of the main renal as well as intra-renal arteries were calculated. Compared with the healthy control subjects, diabetic patients had significantly higher resistivity indices (RIs in the intrarenal (segmental, arcuate and interlobar ar-teries (P= 0.001. The study, also revealed a significantly positive correlation between the RIs in the intrarenal arteries in diabetics and the albumin/creatinine ratio (r= 0.54, 0.52 and 0.51 respectively, glycated hemoglobin (r= 0.61, 0.59 and 0.63 respectively, as well as the estimated GFR (e-GFR (r= 0.53, 0.51 and 0.57 respectively. We conclude that the current study documented early intra-renal hemodynamic alterations in the form of pathologically elevated intrarenal RIs. This denotes the potential usefulness of duplex evaluation of the intrarenal arteries, as a noninvasive procedure, for monitoring type 1 diabetic patients to predict those at risk of diabetic nephropathy.

  7. Eriodictyol prevents early retinal and plasma abnormalities in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Bucolo, Claudio; Leggio, Gian Marco; Drago, Filippo; Salomone, Salvatore

    2012-07-01

    Diabetic retinopathy is a complex disease that has potential involvement of inflammatory and oxidative stress-related pathways in its pathogenesis. We hypothesized that eriodictyol, one of the most abundant dietary flavonoids, could be effective against diabetic retinopathy, which involves significant oxidative stress and inflammation. The aim of the present study was to investigate the effects of eriodictyol in early retinal and plasma changes of streptozotocin-induced diabetic rats. The effect of eriodictyol treatment (0.1, 1, 10 mg/kg daily for 10 days) was evaluated by TNF-α, ICAM-1, VEGF, and eNOS protein levels measurement in the retina, plasma lipid peroxidation, and blood-retinal barrier (BRB) integrity. Increased amounts of cytokines, adhesion molecule, and nitric oxide synthase were observed in retina from diabetic rats. Eriodictyol treatment significantly lowered retinal TNF-α, ICAM-1, VEGF, and eNOS in a dose-dependent manner. Further, treatment with eriodictyol significantly suppressed diabetes-related lipid peroxidation, as well as the BRB breakdown. These data demonstrated that eriodictyol attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the BRB in early diabetic rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Serum Cystatin C as an Early Diagnostic Biomarker of Diabetic Kidney Disease in Type 2 Diabetic Patients.

    Science.gov (United States)

    Qamar, Ayesha; Hayat, Asma; Ahmad, Tariq Mahmood; Khan, Alamgir; Hasnat, Mohammad Najam Ul; Tahir, Sufyan

    2018-04-01

    To determine the diagnostic accuracy and cut-off values of serum cystatin C as early diagnostic biomarker of diabetic kidney disease. Cross-sectional analytical study. Department of Pathology, Army Medical College, Rawalpindi in collaboration with Endocrinology Department, Military Hospital (MH), Rawalpindi from November 2015 to November 2016. One hundred and nineteen diagnosed patients of type 2 diabetes mellitus were enrolled in the study from the outpatient Endocrinology Department of the MH Rawalpindi. Fifty disease-free controls were also included. Fasting blood samples of the patients and controls were analysed for creatinine by Jaffé's kinetic method and estimated GFR was calculated using MDRD-based equation for GFR. Serum cystatin C was estimated by quantitative turbidimetric method. Serum cystatin C was higher in the diabetic group (mean = 1.022 ±0.33 mg/dl) as compared to the control group (mean = 0.63 ±0.14 mg/dl). ROC curve analysis, keeping less than 60 ml/min/1.73 m2 GFR (CKD-MDRD based) as reference value of the stat variable/gold standard; revealed an area under the curve of 0.914 (95% CI 0.85-0.98) and at optimal sensitivity of 88.2% and specificity of 84.8% the established cut-off of serum cystatin C was 1.26 mg/L. Cystatin C is an accurate biomarker of diabetic kidney disease with good sensitivity and specificity.

  9. Early feeding and risk of type 1 diabetes

    DEFF Research Database (Denmark)

    Knip, Mikael; Virtanen, Suvi M; Becker, Dorothy

    2011-01-01

    recruited 5606 newborn infants with a family member affected by type 1 diabetes and enrolled 2159 eligible subjects who carried a risk-conferring HLA genotype. All recruited mothers were encouraged to breastfeed. The intervention lasted for 6-8 mo with a minimum study formula exposure time of 2 mo......, and hydrolyzed casein and standard cow milk-based weaning formulas were compared. Eighty percent of the participants were exposed to the study formula. The overall retention rate over the first 5 y was 87%, and protocol compliance was 94%. The randomization code will be opened when the last recruited child turns...

  10. Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism

    DEFF Research Database (Denmark)

    Hernández-Alvarez, María Isabel; Díaz-Ramos, Angels; Berdasco, María

    2017-01-01

    The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused...... of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes....

  11. The benefit of early treatment without rescreening in women with a history of gestational diabetes.

    LENUS (Irish Health Repository)

    Maher, Nicola

    2013-02-01

    In this center, women with a history of gestational diabetes (GDM) are treated without rescreening from early pregnancy in any subsequent pregnancies, commencing with a low glycemic diet and insulin if and when indicated. The objective of this study was to see if this practice reduced the incidence of macrosomia compared with the index pregnancy.

  12. Early Detection and Treatment of Type 2 Diabetes Reduce Cardiovascular Morbidity and Mortality

    DEFF Research Database (Denmark)

    Herman, William H; Ye, Wen; Griffin, Simon J

    2015-01-01

    OBJECTIVE To estimate the benefits of screening and early treatment of type 2 diabetes compared with no screening and late treatment using a simulation model with data from the ADDITION-Europe study. RESEARCH DESIGN AND METHODS We used the Michigan Model, a validated computer simulation model, an...

  13. Prediction of preeclampsia in type 1 diabetes in early pregnancy by clinical predictors

    DEFF Research Database (Denmark)

    Vestgaard, Marianne; Sommer, Miriam Colstrup; Ringholm, Lene

    2018-01-01

    PURPOSE: The purpose of this study is to evaluate the prevalence and possible clinical predictors of preeclampsia present in early pregnancy among women with type 1 diabetes. METHODS: A systematic search of PubMed was conducted in April 2017. Inclusion criteria were largely unselected cohort, inc...

  14. ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Dhandapany, Perundurai Subramaniam; Ahluwalia, Tarun Veer Singh

    2008-01-01

    The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM).......The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM)....

  15. Delayed recognition of Wolfram syndrome frequently misdiagnosed as type 1 diabetes with early chronic complications.

    Science.gov (United States)

    Zmyslowska, A; Borowiec, M; Fichna, P; Iwaniszewska, B; Majkowska, L; Pietrzak, I; Szalecki, M; Szypowska, A; Mlynarski, W

    2014-01-01

    Improvements in diagnostic methods and greater genetic awareness have brought remarkable progress in the recognition of monogenic forms of diabetes, including Wolfram syndrome (WFS). WFS is diagnosed based on clinical criteria of coexistence of diabetes mellitus and optic atrophy, and confirmed by molecular analysis; however, the condition is still sometimes misdiagnosed. To begin to understand the reasons for misdiagnosis, we conducted a retrospective analysis of WFS patients who were originally misdiagnosed. The medical histories of 13 pediatric patients with clinical misdiagnosis of type 1 diabetes and early chronic complications made in the years 1995-2010 and who were subsequently correctly diagnosed with WFS based on genetic testing in 2008-2011 were analyzed. The average age of the patients at diabetes onset was 5 (4.4-6.3) years, and the mean HbA1c level at diagnosis was 9.1±2.3%. Initially, all of these patients were treated as having type 1 diabetes with progressive visual impairment despite good metabolic control (mean HbA1c 7.5±1.3%). Diagnosis of optic atrophy was made at an average age of 9 (5.9-11.5) years, which corresponds to 4 years after diabetes recognition (p=0.002). At the time of genetic analysis, the average age of the patients was 16 (12-18.7) years, which corresponds to 7 years after recognition of coexistence of diabetes mellitus and optic atrophy (p=0.007). Delays of at least 7 years occurred before recognition of WFS among a cohort of pediatric patients with diabetes. All patients with WFS were primarily misdiagnosed as having type 1 diabetes. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  16. Advantages of early diagnosis of diabetic neuropathy in the prevention of diabetic foot ulcers.

    Science.gov (United States)

    Sanz-Corbalán, Irene; Lázaro-Martínez, José Luis; García-Morales, Esther; Molines-Barroso, Raúl; Álvaro-Afonso, Francisco; García-Álvarez, Yolanda

    2017-12-26

    to evaluate the utility of the sudomotor function test (SFT) as a clinical tool in the Risk Stratification System of diabetic patients and to demonstrate the earlier detection of the risk of developing diabetic foot ulcers (DFU) compared to the standard clinical tests. prospective follow-up study on 263 patients enrolled consecutively over 3.5 years. Diabetic patients without active DFU were classified according to the International Working Group Risk Stratification System (RSS) and categorized according to the results of the Semmes-Wenstein Monofilament (SWM) and biothesiometer measurements or the SFT. The main outcome evaluated was the development of DFU. median follow-up was 42 [38-44] months. Sixty patients (22.8%) developed DFU after a median of 6.2 [3-17] months. Ten patients that were included in the no-risk group (group 0) based on the SWM and biothesiometer results developed DFU. Thus the sensitivity of this approach was 83.33% and the specificity was 50.47%. Based on the SFT results, all patients that developed DFU were included in the correct risk group. This approach had 100% sensitivity and 31.53% specificity. Regarding the diagnostic accuracy of the two Methods, the respective AUC values were 0.776 (95% CI 0.702-0.849) and 0.816 (95% CI 0.757-0.874). SFT improved RSS in diabetic patients in a specialized diabetic foot unit. SFT categorized patients correctly according to the risk of developing DFU. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes.

    Science.gov (United States)

    Bjerregaard, Lise G; Jensen, Britt W; Ängquist, Lars; Osler, Merete; Sørensen, Thorkild I A; Baker, Jennifer L

    2018-04-05

    Childhood overweight is associated with an increased risk of type 2 diabetes in adulthood. We investigated whether remission of overweight before early adulthood reduces this risk. We conducted a study involving 62,565 Danish men whose weights and heights had been measured at 7 and 13 years of age and in early adulthood (17 to 26 years of age). Overweight was defined in accordance with Centers for Disease Control and Prevention criteria. Data on type 2 diabetes status (at age ≥30 years, 6710 persons) were obtained from a national health registry. Overweight at 7 years of age (3373 of 62,565 men; 5.4%), 13 years of age (3418 of 62,565; 5.5%), or early adulthood (5108 of 62,565; 8.2%) was positively associated with the risk of type 2 diabetes; associations were stronger at older ages at overweight and at younger ages at diagnosis of type 2 diabetes. Men who had had remission of overweight before the age of 13 years had a risk of having type 2 diabetes diagnosed at 30 to 60 years of age that was similar to that among men who had never been overweight (hazard ratio, 0.96; 95% confidence interval [CI], 0.75 to 1.21). As compared with men who had never been overweight, men who had been overweight at 7 and 13 years of age but not during early adulthood had a higher risk of type 2 diabetes (hazard ratio, 1.47; 95% CI, 1.10 to 1.98), but their risk was lower than that among men with persistent overweight (hazard ratio [persistently overweight vs. never overweight], 4.14; 95% CI, 3.57 to 4.79). An increase in body-mass index between 7 years of age and early adulthood was associated with an increased risk of type 2 diabetes, even among men whose weight had been normal at 7 years of age. Childhood overweight at 7 years of age was associated with increased risks of adult type 2 diabetes only if it continued until puberty or later ages. (Funded by the European Union.).

  18. Catecholamine induced cardiomyopathy in pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Ron Thomas Varghese

    2013-01-01

    Full Text Available Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. Earlier studies have reported left ventricular dysfunction in around 10% of subjects with pheochromocytoma. [1] Catecholamine induced vasoconstriction, direct toxic effect of byproducts of catecholamine degradation and direct receptor-mediated mechanisms are thought to contribute to cardiomyopathy in subjects with pheochromocytoma. The presentation remains a diagnostic challenge as patients may already have hypertensive heart disease and acute coronary syndrome on account of uncontrolled secondary hypertension. We report a case of a 42-year-old male, who presented with features of pheochromocytoma induced cardiomyopathy.

  19. Microfibrillar cardiomyopathy: A rare case

    Directory of Open Access Journals (Sweden)

    Narender Kumar

    2011-01-01

    Full Text Available Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM. The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.

  20. The Prognostic Value of Right Ventricular Deformation Imaging in Early Arrhythmogenic Right Ventricular Cardiomyopathy.

    Science.gov (United States)

    Mast, Thomas P; Taha, Karim; Cramer, Maarten J; Lumens, Joost; van der Heijden, Jeroen F; Bouma, Berto J; van den Berg, Maarten P; Asselbergs, Folkert W; Doevendans, Pieter A; Teske, Arco J

    2018-03-09

    The aim of this study was to investigate the prognostic value of echocardiographic deformation imaging in arrhythmogenic right ventricular cardiomyopathy (ARVC) to optimize family screening protocols. ARVC is characterized by variable disease expressivity among family members, which complicates family screening protocols. Previous reports have shown that echocardiographic deformation imaging detects abnormal right ventricular (RV) deformation in the absence of established disease expression in ARVC. First-degree relatives of patients with ARVC were evaluated according to 2010 task force criteria, including RV deformation imaging (n = 128). Relatives fulfilling structural task force criteria were excluded for further analysis. At baseline, deformation patterns of the subtricuspid region were scored as type I (normal deformation), type II (delayed onset, decreased systolic peak, and post-systolic shortening), or type III (systolic stretching and large post-systolic shortening). The final study population comprised relatives who underwent a second evaluation during follow-up. Disease progression was defined as the development of a new 2010 task force criterion during follow-up that was absent at baseline. Sixty-five relatives underwent a second evaluation after a mean follow-up period of 3.7 ± 2.1 years. At baseline, 28 relatives (43%) had normal deformation (type I), and 37 relatives (57%) had abnormal deformation (type II or III) in the subtricuspid region. Disease progression occurred in 4% of the relatives with normal deformation at baseline and in 43% of the relatives with abnormal deformation at baseline (p values of abnormal deformation were, respectively, 43% (95% confidence interval: 27% to 61%) and 96% (95% confidence interval: 82% to 100%). Normal RV deformation in the subtricuspid region is associated with absence of disease progression during nearly 4-year follow-up in relatives of patients with ARVC. Abnormal RV deformation seems to precede the

  1. Methodology and early findings of the Diabetes Management Project: a cohort study investigating the barriers to optimal diabetes care in diabetic patients with and without diabetic retinopathy.

    Science.gov (United States)

    Lamoureux, Ecosse Luc; Fenwick, Eva; Xie, Jing; Mcauley, Annie; Nicolaou, Theona; Larizza, Melanie; Rees, Gwyn; Qureshi, Salmaan; Wong, Tien Yin; Benarous, Rehab; Dirani, Mohamed

    2012-01-01

    The Diabetes Management Project is investigating the clinical, behavioural and psychosocial barriers to optimal diabetes care in individuals with and without diabetic retinopathy. Prospective cohort. Two hundred and twenty-three and 374 patients without and with diabetic retinopathy, respectively. All individuals underwent a comprehensive dilated eye test, anthropometric measurements, blood and urine samples, and psychosocial questionnaires. Good glycaemic control was defined as glycosylated haemoglobin Management Project, developed to assess factors associated with suboptimal diabetes care. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

  2. Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy.

    Science.gov (United States)

    Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2017-12-01

    To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR). Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined. The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

  3. Early life treatment with vancomycin reduces diabetes incidence in NOD mice

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Nielsen, Dennis Sandris; Vogensen, Finn Kvist

    Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulato...... of the mechanisms regulating intestinal immune homeostasis toward a proinflammatory mucosal environment.......Type 1 diabetes (T1D) results from an uncontrolled T cell mediated destruction of the insulin-producing beta-cells in the pancreas. Causal factors include a combination of genetics, early life incidents and the food we eat. The involved adaptive immune response can be down regulated by a regulatory...... immune response and a fine-tuned balance between these immunological components is crucial for characteristics of the disease, such as severity, onset time and recovery. The balance between the regulatory and the adaptive immune response is heavily influenced by early life bacterial stimulation...

  4. Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Bruce A Perkins

    Full Text Available To determine the role of markers of plasma protein damage by glycation, oxidation and nitration in microalbuminuria onset or subsequent decline of glomerular filtration rate (termed "early GFR decline" in patients with type 1 diabetes.From the 1(st Joslin Kidney Study, we selected 30 patients with longstanding normoalbuminuria and 55 patients with new onset microalbuminuria. Patients with microalbuminuria had 8-12 years follow-up during which 33 had stable GFR and 22 early GFR decline. Mean baseline GFR(CYSTATIN C was similar between the three groups. Glycation, oxidation and nitration markers were measured in protein and ultrafiltrate at baseline by liquid chromatography-tandem mass spectrometry using the most reliable methods currently available.Though none were significantly different between patients with microalbuminuria with stable or early GFR decline, levels of 6 protein damage adduct residues of plasma protein and 4 related free adducts of plasma ultrafiltrate were significantly different in patients with microalbuminuria compared to normoalbuminuria controls. Three protein damage adduct residues were decreased and 3 increased in microalbuminuria while 3 free adducts were decreased and one increased in microalbuminuria. The most profound differences were of N-formylkynurenine (NFK protein adduct residue and N(ω-carboxymethylarginine (CMA free adduct in which levels were markedly lower in microalbuminuria (P<0.001 for both.Complex processes influence levels of plasma protein damage and related proteolysis product free adducts in type 1 diabetes and microalbuminuria. The effects observed point to the possibility that patients who have efficient mechanisms of disposal of damaged proteins might be at an increased risk of developing microalbuminuria but not early renal function decline. The findings support the concept that the mechanisms responsible for microalbuminuria may differ from the mechanisms involved in the initiation of early

  5. Role of Electrophysiology in the Early Diagnosis and Follow-Up of Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Nicola Pescosolido

    2015-01-01

    Full Text Available Retinopathy is a severe and common complication of diabetes, representing a leading cause of blindness among working-age people in developed countries. It is estimated that the number of people with diabetic retinopathy (DR will increase from 126.6 million in 2011 to 191 million by 2030. The pathology seems to be characterized not only by the involvement of retinal microvessels but also by a real neuropathy of central nervous system, similar to what happens to the peripheral nerves, particularly affected by diabetes. The neurophysiological techniques help to assess retinal and nervous (optic tract function. Electroretinography (ERG and visual evoked potentials (VEP allow a more detailed study of the visual function and of the possible effects that diabetes can have on the visual function. These techniques have an important role both in the clinic and in research: the central nervous system, in fact, has received much less attention than the peripheral one in the study of the complications of diabetes. These techniques are safe, repeatable, quick, and objective. In addition, both the ERG (especially the oscillatory potentials and the flicker-ERG and VEP have proved to be successful tools for the early diagnosis of the disease and, potentially, for the ophthalmologic follow-up of diabetic patients.

  6. An Early Detection Method of Type-2 Diabetes Mellitus in Public Hospital

    Directory of Open Access Journals (Sweden)

    Hermansyah Hermansyah

    2011-08-01

    Full Text Available Diabetes is a chronic disease and major problem of morbidity and mortality in developing countries. The International Diabetes Federation estimates that 285 million people around the world have diabetes. This total is expected to rise to 438 million within 20 years. Type-2 diabetes mellitus (T2DM is the most common type of diabetes and accounts for 90-95% of all diabetes. Detection of T2DM from various factors or symptoms became an issue which was not free from false presumptions accompanied by unpredictable effects. According to this context, data mining and machine learning could be used as an alternative way help us in knowledge discovery from data. We applied several learning methods, such as instance based learners, naive bayes, decision tree, support vector machines, and boosted algorithm acquire information from historical data of patients medical records of Mohammad Hoesin public hospital in Southern Sumatera. Rules are extracted from Decision tree to offer decision-making support through early detection of T2DM for clinicians.

  7. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice

    DEFF Research Database (Denmark)

    Pinto, Yigal M; Elliott, Perry M; Arbustini, Eloisa

    2016-01-01

    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis...

  8. Early and late scanning electron microscopy findings in diabetic kidney disease.

    Science.gov (United States)

    Conti, Sara; Perico, Norberto; Novelli, Rubina; Carrara, Camillo; Benigni, Ariela; Remuzzi, Giuseppe

    2018-03-20

    Diabetic nephropathy (DN), the single strongest predictor of mortality in patients with type 2 diabetes, is characterized by initial glomerular hyperfiltration with subsequent progressive renal function loss with or without albuminuria, greatly accelerated with the onset of overt proteinuria. Experimental and clinical studies have convincingly shown that early interventions retard disease progression, while treatment if started late in the disease course seldom modifies the slope of GFR decline. Here we assessed whether the negligible renoprotection afforded by drugs in patients with proteinuric DN could be due to loss of glomerular structural integrity, explored by scanning electron microscopy (SEM). In diabetic patients with early renal disease, glomerular structural integrity was largely preserved. At variance SEM documented that in the late stage of proteinuric DN, glomerular structure was subverted with nearly complete loss of podocytes and lobular transformation of the glomerular basement membrane. In these circumstances one can reasonably imply that any form of treatment, albeit personalized, is unlikely to reach a given cellular or molecular target. These findings should persuade physicians to start the putative renoprotective therapy soon after the diagnosis of diabetes or in an early phase of the disease before structural integrity of the glomerular filter is irreversibly compromised.

  9. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    Science.gov (United States)

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (PM. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

  10. Randomized Efficacy Trial of Early Preconception Counseling for Diabetic Teens (READY-Girls)

    OpenAIRE

    Charron-Prochownik, Denise; Ferons-Hannan, Margaret; Sereika, Susan; Becker, Dorothy

    2008-01-01

    OBJECTIVE?To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls). RESEARCH DESIGN AND METHODS?A total of 53 adolescent females with type 1 diabetes between 16 and 19.9 years of age were randomized into groups receiving a CD-ROM, a book, or standard care (control) and given one comprehensive session. Outcomes were assessed at baseline, immediately after, a...

  11. Genetics of cardiomyopathies in children

    Directory of Open Access Journals (Sweden)

    Matteo Vatta

    2011-08-01

    Full Text Available Cardiomyopathies are diseases of the heart muscle leading to heart failure and/or an increased risk of arrhythmogenic sudden cardiac death. These disorders represent a major cause of morbidity and mortality in children. In childhood forms of cardiomyopathy, genetic etiologies are frequent, but non-genetic or acquired causes, such viral infection, also play a significant role. In the last twenty years, the genetic causes of cardiomyopathies have been increasingly identified and clinical correlations are beginning to be defined. Here we present an overview of the recent advances in our understanding of the genetics of cardiomyopathies in children and what is known about the pathophysiological mechanisms underlying these gene-related forms of disease.

  12. Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature.

    Science.gov (United States)

    Eliades, Myrto; El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D

    2014-02-01

    Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity.

  13. Cell therapy in dilated cardiomyopathy: from animal models to clinical trials

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    C. del Corsso

    2011-05-01

    Full Text Available Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases.

  14. Can ultrasound abdomen help in early diagnosis of diabetes mellitus? an observational study

    International Nuclear Information System (INIS)

    Anwar, J.; Aamir, M.O.; Imdad, Z.U.H.

    2015-01-01

    Diabetes mellitus is a common disease. Similarly, ultrasound findings of fatty change and renal crystals are commonly seen on ultrasound. In the personal observation of the main author over the past so many years it was noticed that Diabetes Mellitus, Fatty liver and renal crystals all sit well together. This study tries to establish a relationship between diabetes mellitus renal echogenic foci and fatty liver. This study is first of its kind, as nobody has ever before investigated an association between the renal echogenic foci and fatty liver in relation to diabetes mellitus. Methods: This cross-sectional, observational study was conducted at Radiology Department Combined Military Hospital, Kohat From 2nd June 2013 to 30th May 2014. Three hundred patients were collected on the basis of having fatty liver and renal echogenic foci on ultrasound and three hundred more patients were collected who had no fatty liver or renal echogenic foci on ultrasound. Their labs were done for diabetes mellitus. Results: The patients having renal echogenic foci together with fatty liver had 83% positive rate of being diabetics, while patients with no fatty liver and no echogenic foci on ultrasonography had only 0.6% Positive rate of being diabetics. Conclusion: Our results provided the first demonstration of an association between renal echogenic foci together with fatty liver with the diabetes mellitus. Thus ultrasound examination of abdomen can be helpful in its early diagnosis if we make a protocol of doing fasting and random blood sugars in all those patients who have positive renal echogenic foci and fatty liver on their ultrasound examination. (author)

  15. Associations of Fetuin-A levels with vascular disease in type 2 diabetes patients with early diabetic nephropathy

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    Roos Marcel

    2010-09-01

    Full Text Available Abstract Background Ambigous results exist on fetuin-A as marker for vascular disease in type 2 diabetes. This study aims to define the role of fetuin-A as marker for micro- and macrovascular disease in a high risk population of patients with type 2 diabetes mellitus and early diabetic nephropathy. Methods Fetuin-A serum levels were assessed by ELISA in a cross-sectional setting in 153 patients with type 2 diabetes. Associations of fetuin-A with metabolic, inflammatory and vascular markers were studied. Atherosclerotic burden was assessed by ankle-brachial-index (ABI as well as detection of common carotid artery intima-media thickness (IMT. Results Levels of fetuin-A were lower in male than in female patients (0.49 ± 0.15 vs. 0.56 ± 0.20 g/L, p = 0.02. In addition, there was an inverse correlation with age (r = -0.20, P = 0.01. Bivariate correlations adjusted for age and gender revealed no significant correlations with metabolic parameters, except for a weak inverse correlation with serum adiponectin (r = -0.19, p = 0.02. Regarding parameters of micro- and macrovascular disease, fetuin-A was significantly associated with ABI (r = 0.18, p = 0.04, while there was no association with IMT (r = -0.07, p = n.s. Patients with an ABI 1.3 (0.43 ± 0.10 vs. 0.52 ± 0.17 vs. 0.54 ± 0.18 g/L p = 0.05. Neither GFR nor albuminuria were associated with fetuin-A serum levels. Patients with prevalent neuropathy did not have altered fetuin-A levels compared to diabetic controls. In step-wise logistic regression analysis including age, gender, HbA1c, total cholesterol, glomerular filtration rate and fetuin-A, only total cholesterol (β = 0.01, p = 0.02 and fetuin-A (β = -5.99, p = 0.03 proved to be independent predictors of an ABI Conclusions The results of this cross-sectional study suggest that lower fetuin-A levels are associated with macrovascular late complications in high-risk type 2 diabetes patients while there are no associations of fetuin-A with

  16. Early detection and prevention of diabetic nephropathy: a challenge calling for mandatory action for Mexico and the developing world.

    Science.gov (United States)

    Correa-Rotter, Ricardo; González-Michaca, Luis

    2005-09-01

    During the last decades, developing countries have experienced an epidemiologic transition characterized by a reduction of infectious diseases and an increase of chronic degenerative diseases. This situation is generating tormenting public health, financial, and social consequences. Of particular relevance is type 2 diabetes mellitus and its chronic complications, particularly cardiovascular disease and diabetic nephropathy, because mortality of the patient with diabetes is, in most instances, related to these complications. There is a clear need to implement diagnostic and treatment strategies to reduce risk factors for development of diabetes (primary prevention), to detect risk factors of chronic complications in early stages of diabetes (secondary prevention), and to prevent further progression of those that already have renal injury (tertiary prevention). Microalbuminuria is an early marker of renal injury in diabetes, and its early detection can help the timely use of renal preventive measures, which would avoid the extremely high costs of renal replacement treatment for end-stage renal disease as well as that of other cardiovascular complications. Preventive strategies are of very little or no impact, if the primary physician has limited knowledge about the natural history of diabetic nephropathy, the beneficial effect of early preventive maneuvers for delaying its progression, and the social and economic impact of end-stage renal disease. It is therefore imperative to assure in our health systems that general practitioners have the ability and commitment to detect early diabetes complications, in order to promote actions that support regression or retard highly morbid cardiovascular and renal conditions.

  17. Deep Convolutional Neural Network-Based Early Automated Detection of Diabetic Retinopathy Using Fundus Image.

    Science.gov (United States)

    Xu, Kele; Feng, Dawei; Mi, Haibo

    2017-11-23

    The automatic detection of diabetic retinopathy is of vital importance, as it is the main cause of irreversible vision loss in the working-age population in the developed world. The early detection of diabetic retinopathy occurrence can be very helpful for clinical treatment; although several different feature extraction approaches have been proposed, the classification task for retinal images is still tedious even for those trained clinicians. Recently, deep convolutional neural networks have manifested superior performance in image classification compared to previous handcrafted feature-based image classification methods. Thus, in this paper, we explored the use of deep convolutional neural network methodology for the automatic classification of diabetic retinopathy using color fundus image, and obtained an accuracy of 94.5% on our dataset, outperforming the results obtained by using classical approaches.

  18. Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

    Science.gov (United States)

    Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

    2017-07-01

    This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

  19. Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes.

    Science.gov (United States)

    Bernstein, Judith A; McCloskey, Lois; Gebel, Christina M; Iverson, Ronald E; Lee-Parritz, Aviva

    2016-01-01

    Gestational diabetes mellitus (GDM) greatly increases the risk of developing diabetes in the decade after delivery, but few women receive appropriately timed postpartum glucose testing (PPGT) or a referral to primary care (PC) for continued monitoring. This qualitative study was designed to identify barriers and facilitators to testing and referral from patient and providers' perspectives. We interviewed patients and clinicians in depth about knowledge, values, priorities, challenges, and recommendations for increasing PPGT rates and PC linkage. Interviews were coded with NVIVO data analysis software, and analyzed using an implementation science framework. Women reported motivation to address GDM for the health of the fetus. Most women did not anticipate future diabetes for themselves, and focused on delivery outcomes rather than future health risks. Patients sought and received reassurance from clinicians, and were unlikely to discuss early onset following GDM or preventive measures. PPGT barriers described by patients included provider not mentioning the test or setting it up, transportation difficulties, work responsibilities, fatigue, concerns about fasting while breastfeeding, and timing of the test after discharge from obstetrics, and no referral to PC for follow-up. Practitioners described limited communication among multiple care providers during pregnancy and delivery, systems issues, and separation of obstetrics from PC. Patients' barriers to PPGT included low motivation for self-care, structural obstacles, and competing priorities. Providers reported the need to balance risk with reassurance, and identified systems failures related to test timing, limitations of electronic medical record systems (EMR), lack of referrals to PC, and inadequate communication between specialties. Prevention of early onset has great potential for medical cost savings and improvements in quality of life.

  20. Trends in Early Prenatal Care Among Women with Pre-Existing Diabetes: Have Income Disparities Changed?

    Science.gov (United States)

    Breathett, Khadijah; Filley, Jessica; Pandey, Madhaba; Rai, Nayanjot; Peterson, Pamela N

    2018-01-01

    Women with pre-existing diabetes are at high maternal risk for comorbidities and death, particularly when early prenatal care is not received. Low income is a known barrier to early prenatal care. It is unknown whether recent policies to expand access to prenatal care have reduced income disparities. We hypothesized that income disparities would be minimized and that the odds of receipt of first trimester prenatal care among women with pre-existing diabetes would become similar across income strata over time. Using the Colorado birth certificate registry from 2007 to 2014, receipt of prenatal care was assessed retrospectively in 2,497 women with pre-existing diabetes. Logistic regression was used to examine the association between high (>$50,000), medium ($25,000-50,000), and low (prenatal care by birth year, adjusted for demographics. High, medium, and low income represented 29.5%, 19.0%, and 51.5% of the cohort, respectively. Women with high income were more likely to receive first trimester care than women with low income from 2007 [adjusted odds ratio, 95% confidence interval: 2.16 (1.18, 3.96)] through 2013 [1.66 (1.01, 2.73)], but significant differences were no longer observed in 2014 [1.59 (0.89, 2.84)]. The likelihood of receiving first trimester prenatal care was not significantly different between medium- and low-income strata from 2007 [1.07 (0.66, 1.74)] through 2014 [0.77 (0.48, 1.23)]. From 2007 to 2013, women in Colorado with diabetes were more likely to receive early prenatal care if they were in the highest income stratum than in the lowest stratum. In 2014, receipt of first trimester care became equitable across all income strata. Future work should examine national patterns of income with receipt of prenatal care and outcomes among women with pre-existing diabetes.

  1. Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin

    Directory of Open Access Journals (Sweden)

    Resham R Poudel

    2012-01-01

    Full Text Available Approximately 10% of phenotypic type 2 diabetics have islet autoantibodies and are referred to as having latent autoimmune diabetes of adults (LADA, and they land on early sulfonylurea failure and require insulin. Diagnosing LADA has treatment implications because of high risk of progression to insulin dependency. But often there is delay in insulin therapy, as there are no recommendations for islet antibody testing in adult-onset diabetes currently. LADA clinical risk score can identify adults at high risk who may benefit from antibody testing. The optimal treatment of LADA is not established. Early insulin therapy helps to achieve good metabolic control and better long-term outcomes by preserving b-cells and endogenous C-peptide secretion. Sulfonylureas are better avoided as they exhaust b-cells; glitazones and exenatide have favorable outcomes, whereas metformin needs to be used with caution. Understanding LADA will also bring new windows in managing type 1 diabetes. Information acquisition was done by reviewing the medical literature published since 1987, with particular attention to the natural history, genetic factors, and treatment of LADA.

  2. Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

    Science.gov (United States)

    Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

    2013-10-01

    To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

  3. Study on the mechanism of retinal ganglion cell apoptosis in early stage of diabetic rats

    Directory of Open Access Journals (Sweden)

    Rui-Dong Gu

    2014-03-01

    Full Text Available AIM: To investigate the mechanism of retinal ganglion cell apoptosis in early stage of streptozotocin(STZ-induced diabetic rats. METHODS: Sixty SD rats were randomly divided into two groups: control group(CONand diabetes mellitus group(DM. Diabetic rat model was produced by intraperitoneal injection of 1% STZ in 30 adult male SD rats. At 4, 8, 12wk,the rats were killed and eyeballs were enucleated for the HE staining, TUNEL staining, transmission electron microscopy detection respectively, and laser confocal microscope detection was used to detect the calcium ion concentration.RESULTS:At 8wk RGCs decreased gradually and appeared disordered arrangement and got worse at 12wk in DM group. In DM group, mitochondrial swelling was detected at 4wk., and became more obvious, more in number at 8wk with reduction in some cells' volume and the number of organelles decreased. In DM group, few TUNEL positive RGCs were seen at 4wk, and became more and more at 8 and 12wk. The apoptosis index was significantly higher in DM group compared with CON group in different time points(PPPCONCLUSION: The study suggested that RGCs apoptosis occurs in early stage of diabetes, the mechanism might be associated with increased intracellular calcium ion concentration.

  4. Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

    Science.gov (United States)

    Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

    2016-09-01

    Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

  5. Treatment of early complications on eye fundus in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Iva Akmadža

    2016-09-01

    Full Text Available Early ocular complications in patients with diabetes mellitus (DM mostly refer to non-proliferative diabetic retinopathy (NPDR. Generally speaking, diabetic retinopathy (DR is one of the most common causes of blindness and the most common cause of blindness between the age of 20 and 65. DM is a disease characterized by metabolic disorders of carbohydrates, lipids and proteins. The main characteristic is hyperglycemia, which affects all organs by different pathogenetic pathways. The presence of DR is associated with the duration of DM, glycemic control and blood pressure. DR is a microangiopathy and is diagnosed by simple indirect ophthalmoscopy. It is very important to perform regular eye examinations in patients with DM, whereas DR is usually asymptomatic in the early stage of the disease. Optical coherence tomography (OCT has the great importance in diagnostics of DR. Besides indirect ophthalmoscopy and OCT, fluorescein angiography and ultrasound are also widely used to diagnose DR. The prevention of the disease is most important, which is in domain of internal medicine specialist, diabetologist and general practitioner. Intravitreal anti-vascular endothelial growth factor therapy is the gold standard in treatment of NPDR associated with diabetic macular edema (DME and impaired vision. Intravitreal injections of corticosteroids and laser photocoagulation are also used. The current and future treatment modalities are presented in the text that follows.

  6. Type 2 diabetes mellitus with early phase acute inflammatory protein on serum protein electrophoresis

    Directory of Open Access Journals (Sweden)

    ET Tuladhar

    2012-03-01

    Full Text Available Background: The onset of Type 2 diabetes has been associated with low grade systemic inflammation. The inflammatory status has been studied by measuring acute phase reactant proteins like hsCRP, α1- antitrypsin, α1-acid glycoprotein, ceruloplasmin, fibrinogen. Most of these acute phase reactants form α1 and α2 bands on electropherogram of serum proteins. The aim of this study was to evaluate inflammatory status in controlled and uncontrolled type 2 diabetes using cellulose acetate electrophoresis and to find the impact of glycemic status as indicated by HbA1c on inflammation process. Materials and Methods: Serum protein electrophoresis was done on serum samples of 60 cases of Diabetes [controlled and uncontrolled] using cellulose acetate paper technique. The electropherogram obtained was stained with Ponseu S and then quantitated using densitometer. Glycemic status was studied by HbA1c analysis. The density of α1and α2 bands in electropherogram were correlated with HbA1c level. Result: A significant increase in the percentage of α1 and α2 band proteins (0.765 and 0.716, p<0.001 were found with the increasing level of HbA1c. With cutoff of HbA1c 7% (American Diabetic Association recommended, the α1 and α2 serum proteins concentration are significantly higher (p<0.001 in uncontrolled diabetes mellitus compared to controlled diabetes mellitus Conclusion: Cellulose acetate electrophoresis of serum proteins show early phase acute inflammatory status in uncontrolled type 2 diabetes mellitus. The process of systemic inflammation worsens with uncontrolled glycemia as indicated by HbA1c. Inflammatory status should be studied adjunct to glycemic status. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6024 JPN 2012; 2(3: 211-214

  7. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Stefania Lucia Nori

    2013-01-01

    Full Text Available Diabetic polyneuropathy (DPN, characterized by early hyperalgesia and increased nerve growth factor (NGF, evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB. In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

  8. Evaluation of serum zonulin for use as an early predictor for gestational diabetes

    OpenAIRE

    Mokkala, K; Tertti, K; R?nnemaa, T; Vahlberg, T; Laitinen, K

    2017-01-01

    Diet has an important role in regulating intestinal permeability and subsequently the risk for metabolic disorders. In this observational study, we examined whether serum intestinal permeability marker zonulin, could be used as a predictor for gestational diabetes mellitus (GDM). Serum zonulin concentration was measured in early pregnancy in overweight or obese pregnant women (n=88) at risk for developing GDM. Serum zonulin was associated with higher odds of GDM (adjusted OR for 1?ng?ml?1 inc...

  9. Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

    NARCIS (Netherlands)

    Kloet, F.M. van der; Tempels, F.W.A.; Ismail, N.; Heijden, R. van der; Kasper, P.T.; Rojas-Cherto, M.; Doorn, R. van; Spijksma, G.; Koek, M.; Greef, J. van der; Mäkinen, V.P.; Forsblom, C.; Holthöfer, H.; Groop, P.H.; Reijmers, T.H.; Hankemeier, T.

    2012-01-01

    Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically

  10. Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

    OpenAIRE

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

    2014-01-01

    In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin...

  11. An analysis on the level changing of UET and SET in blood and urine in early stage of kidney disease caused by diabetes

    International Nuclear Information System (INIS)

    Liu Juzhen; Yang Wenying; Cai Tietie

    2001-01-01

    Objective: To study the relationship between UET and SET variation and early changes of diabetic nephropathy. Methods: UET and SET were measured in 24 patients with diabetes, 19 with early stage diabetic nephropathy, 21 with advanced diabetic nephropathy and 30 normal as contrast. Results: Apparent uprise of UET and SET was observed in all patients when compared to normal contrasts (P 2 -macroglobulin was revealed (P<0.05). Conclusion: UET and SET levels uprose as long as diabetic nephropathy deteriorated. As a result, UET and SET may act as sensitive indices in diagnosing early stage diabetic nephropathy

  12. Inherited cardiomyopathies and sports participation.

    Science.gov (United States)

    Zorzi, A; Pelliccia, A; Corrado, D

    2018-03-01

    Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

  13. Doppler Ultrasound Detection of Preclinical Changes in Foot Arteries in Early Stage of Type 2 Diabetes

    International Nuclear Information System (INIS)

    Leoniuk, Jolanta; Łukasiewicz, Adam; Szorc, Małgorzata; Sackiewicz, Izabela; Janica, Jacek; Łebkowska, Urszula

    2014-01-01

    There are few reports regarding the changes within the vessels in the initial stage of type 2 diabetes. The aim of this study was to estimate the hemodynamic and morphological parameters in foot arteries in type 2 diabetes subjects and to compare these parameters to those obtained in a control group of healthy volunteers. Ultrasound B-mode, color Doppler and pulse wave Doppler imaging of foot arteries was conducted in 37 diabetic patients and 36 non-diabetic subjects to determine their morphological (total vascular diameter and flow lumen diameter) and functional parameters (spectral analysis). In diabetic patients, the overall vascular diameter and wall thickness were statistically significantly larger when compared to the control group in the right dorsalis pedis artery (P=0.01; P=0.001), left dorsalis pedis artery (P=0.007; P=0.006), right posterior tibial artery (P=0.005; P=0.0005), and left posterior tibial artery (P=0.007; P=0.0002). No significant differences were observed in both groups in flow lumen diameters and blood flow parameters (PSV, EDV, PI, RI). In the diabetic group, the level of HbA1c positively correlated with flow resistance index in the right dorsalis pedis artery (r=0.38; P=0.02), right posterior tibial artery (r=0.38; P=0.02) and left posterior tibial artery (r=0.42; P=0.009). The pulsatility index within the dorsalis pedis artery decreased with increased trophic skin changes (r=–0.431, P=0.009). In the diabetic group, overall artery diameters larger than and flow lumina comparable to the control group suggest vessel wall thickening occurring in the early stage of diabetes. Doppler flow parameters are comparable in both groups. In the diabetic group, the level of HbA1c positively correlated with flow resistance index and negative correlation was observed between the intensity of trophic skin changes and the pulsatility index

  14. Risk of Hyperglycemia and Diabetes after Early-Life Famine Exposure: A Cross-Sectional Survey in Northeastern China

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    Yangyu Zhang

    2018-05-01

    Full Text Available Previous studies suggested that malnutrition during early life may play an essential role in later outcomes and disease risk in adulthood. We aimed to investigate the risks of hyperglycemia and diabetes 50 years after early-life famine exposure in a Northeastern Chinese population. We used the data from 5690 adults born between 1956 and 1965 in selected communities from a 2012 cross-sectional study. The early-childhood exposure cohort showed an increased risk of hyperglycemia compared with the unexposed cohort in the female population (odds ratio (OR 1.46; 95% confidence interval (CI 1.04, 2.06. The increased risk of diabetes in the early-childhood and fetal exposure cohorts was 37.0% (95% CI 1.05–1.79 and 50% (95% CI 1.15–1.96, respectively. For women, the risk of diabetes was more pronounced in the fetal-exposed cohort (OR 1.82; 95% CI 1.26–2.63 than in the early-childhood cohort (OR 1.57; 95% CI 1.08–2.26. Early-life exposure to famine increased the risk of diabetes. Furthermore, early-childhood exposure to famine might increase the risk of hyperglycemia in women. A policy for preventing early life malnutrition should be drafted by the government to prevent hyperglycemia and diabetes in adulthood.

  15. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

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    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  16. [Influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma].

    Science.gov (United States)

    Xiong, Tao; Wanggou, Siyi; Li, Xuejun; Liu, Qing; Jiang, Xingjun; Peng, Zefeng; Yuan, Xianrui

    2016-10-28

    To explore the influence of preventive use of vasopressin tannate on diabetes insipidus and serum sodium at the early postoperation of craniopharyngioma.
 Methods: The data of 83 patients, who underwent unilateral sub-frontal approach resection of craniopharyngioma between 2010 and 2014 by the same senior neurosurgeon, were retrospectively analyzed. The patients were divided into a vasopressin tannate group (used group) and a control group. The diabetes insipidus and serum sodium changes were compared between the two groups.
 Results: Compared with the control group, the incidence of diabetes insipidus decreased at the early postoperation in the vasopressin tannate group (Pcraniopharyngioma.

  17. Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes

    DEFF Research Database (Denmark)

    Secher, A L; Madsen, A B; Nielsen, Lene Ringholm

    2012-01-01

    of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found......Aim: To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. Methods: Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring...

  18. Use of intravoxel incoherent motion diffusion-weighted imaging to detect early changes in diabetic kidneys.

    Science.gov (United States)

    Deng, Yi; Yang, Biran; Peng, Yan; Liu, Zhiqiang; Luo, Jinwen; Du, Guoxin

    2018-03-14

    The purpose of the study was to examine differences in kidney intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in early-stage diabetic patients versus healthy controls. Nineteen type 2 diabetic patients (group A) with a urinary albumin-to-creatinine ratio (ACR) diabetic kidney changes was determined by receiver operating characteristic analysis. Three radiologists independently measured the parameters derived from IVIM-DWI in the two groups by free-hand placing regions of interest, and the interclass coefficients (ICCs) were analyzed by SPSS.16.0 software. The f values of the kidneys were significantly higher in diabetic patients than in healthy volunteers. The D value of the kidneys was significantly lower in diabetic patients than in healthy volunteers. No significant differences in the D* values of the kidneys were observed between diabetic patients and healthy volunteers. The D values of the right kidneys were significantly higher than those of the left kidneys in both groups. The results of the receiver operating characteristic analysis were as follows: left kidney-f value AUC = 0.650 (cutoff point ≥ 27.49%) and D value AUC = 0.752 (cutoff point ≤ 1.68 × 10 -3  mm 2 /s); and right kidney-f value AUC = 0.650 (cutoff point ≥ 28.24%) and D value AUC = 0.752 (cutoff point ≤ 1.81 × 10 -3 mm 2 /s). The diagnostic performance of the D* value was very low (AUC  0.05). The ICCs of the f value and D value were between 0.637 and 0.827. The ICC of the D* value was less than 0.3. The results of our study suggest that changes in kidneys detected by IVIM-DWI may serve as indicators of early diabetic kidney disease.

  19. Mutations of maturity-onset diabetes of the young (MODY) genes in Thais with early-onset type 2 diabetes mellitus.

    Science.gov (United States)

    Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapaporn; Sriussadaporn, Sutin; Vannaseang, Sathit; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

    2009-06-01

    Six known genes responsible for maturity-onset diabetes of the young (MODY) were analysed to evaluate the prevalence of their mutations in Thai patients with MODY and early-onset type 2 diabetes. Fifty-one unrelated probands with early-onset type 2 diabetes, 21 of them fitted into classic MODY criteria, were analysed for nucleotide variations in promoters, exons, and exon-intron boundaries of six known MODY genes, including HNF-4alpha, GCK, HNF-1alpha, IPF-1, HNF-1beta, and NeuroD1/beta2, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing. Missense mutations or mutations located in regulatory region, which were absent in 130 chromosomes of non-diabetic controls, were classified as potentially pathogenic mutations. We found that mutations of the six known MODY genes account for a small proportion of classic MODY (19%) and early-onset type 2 diabetes (10%) in Thais. Five of these mutations are novel including GCK R327H, HNF-1alpha P475L, HNF-1alphaG554fsX556, NeuroD1-1972 G > A and NeuroD1 A322N. Mutations of IPF-1 and HNF-1beta were not identified in the studied probands. Mutations of the six known MODY genes may not be a major cause of MODY and early-onset type 2 diabetes in Thais. Therefore, unidentified genes await discovery in a majority of Thai patients with MODY and early-onset type 2 diabetes.

  20. Hypertension in diabetes as related to nephropathy. Early blood pressure changes

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Borch-Johnsen, K; Mathiesen, E R

    1985-01-01

    We measured the blood pressure under standardized conditions in three groups of patients with type I (insulin-dependent) diabetes: group 1, patients with Albustix-negative urine and normal urinary albumin excretion rate below 20 micrograms/min; group 2, patients with Albustix-negative urine and e...... that arterial hypertension is an early feature in the developing of diabetic nephropathy, with blood pressure rising before the presence of clinical proteinuria.......We measured the blood pressure under standardized conditions in three groups of patients with type I (insulin-dependent) diabetes: group 1, patients with Albustix-negative urine and normal urinary albumin excretion rate below 20 micrograms/min; group 2, patients with Albustix-negative urine...... and elevated urinary albumin excretion rate 20 to 200 micrograms/min; and group 3, patients with Albustix-positive urine at the time of diagnosis of diabetic nephropathy, that is, proteinuria greater than 0.5 g/24 hr on four consecutive visits with an interval of more than 1 month. We also studied blood...

  1. Early pregnancy clinical risk factors for preeclampsia in women with type 1 and type 2 diabete

    DEFF Research Database (Denmark)

    Nørgaard, Sidse Kjærhus; Vestergaard, Marianne; Ásbjörnsdóttir, Björg

    Aim: To assess the prevalence of pregnancy-induced hypertensive disorders and to identify early clinical, modifiable predictors of preeclampsia in women with type 1 and type 2 diabetes. Methods: A population-based cohort study of 494 women with pre-existing diabetes (307 type 1 and 187 type 2...... diabetes), included at their first antenatal visit at 11±6 gestational weeks (mean±SD) from 2012 to 2016. Predictors of preeclampsia present at first antenatal visit were sought identified. Results: At the first antenatal visit HbA1c was 6.9±2.3 % (51±10 mmol/mol) vs. 6.8±2.6 % (49±14 mmol/mol) and blood...... pressure 120±12/76±8 mmHg vs. 122±14/79±10 mmHg, (p=0.16/p=0.001) in women with type 1 and type 2 diabetes, respectively. Preeclampsia developed in 40 women at 36±3 gestational weeks with delivery 8±9 days later. The prevalence of preeclampsia was 8% (9% vs. 7%) and gestational hypertension 8% (9% vs. 6...

  2. Continuous glucose monitoring system and new era of early diagnosis of diabetes in high risk groups

    Directory of Open Access Journals (Sweden)

    Ashraf Soliman

    2014-01-01

    Full Text Available Continuous glucose monitoring (CGM systems are an emerging technology that allows frequent glucose measurements to monitor glucose trends in real time. Their use as a diagnostic tool is still developing and appears to be promising. Combining intermittent glucose self-monitoring (SGM and CGM combines the benefits of both. Significant improvement in the treatment modalities that may prevent the progress of prediabetes to diabetes have been achieved recently and dictates screening of high risk patients for early diagnosis and management of glycemic abnormalities. The use of CGMS in the diagnosis of early dysglycemia (prediabetes especially in high risk patients appears to be an attractive approach. In this review we searched the literature to investigate the value of using CGMS as a diagnostic tool compared to other known tools, namely oral glucose tolerance test (OGTT and measurement of glycated hemoglobin (HbA1C in high risk groups. Those categories of patients include adolescents and adults with obesity especially those with family history of type 2 diabetes mellitus, polycystic ovary syndrome (PCO, gestational diabetes, cystic fibrosis, thalassemia major, acute coronary syndrome (ACS, and after renal transplantation. It appears that the ability of the CGMS for frequently monitoring (every 5 min glucose changes during real-life settings for 3 to 5 days stretches the chance to detect more glycemic abnormalities during basal and postprandial conditions compared to other short-timed methods.

  3. Early-Onset Central Diabetes Insipidus due to Compound Heterozygosity for AVP Mutations.

    Science.gov (United States)

    Bourdet, Karine; Vallette, Sophie; Deladoëy, Johnny; Van Vliet, Guy

    2016-01-01

    Genetic cases of isolated central diabetes insipidus are rare, are mostly due to dominant AVP mutations and have a delayed onset of symptoms. Only 3 consanguineous pedigrees with a recessive form have been published. A boy with a negative family history presented polyuria and failure to thrive in the first months of life and was diagnosed with central diabetes insipidus. Magnetic resonance imaging showed a normal posterior pituitary signal. A molecular genetic analysis of the AVP gene showed that he had inherited a previously reported mutation from his Lebanese father and a novel A>G transition in the splice acceptor site of intron 1 (IVS1-2A>G) from his French-Canadian mother. Replacement therapy resulted in the immediate disappearance of symptoms and in weight gain. The early polyuria in recessive central diabetes insipidus contrasts with the delayed presentation in patients with monoallelic AVP mutations. This diagnosis needs to be considered in infants with very early onset of polyuria-polydipsia and no brain malformation, even if there is no consanguinity and regardless of whether the posterior pituitary is visible or not on imaging. In addition to informing family counseling, making a molecular diagnosis eliminates the need for repeated imaging studies. © 2015 S. Karger AG, Basel.

  4. TREATMENT OF PERIPARTUM CARDIOMYOPATHY (REVIEW

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    N. T. Vatutin

    2017-01-01

    Full Text Available The presented review concerns discussion about current insights into treatment of peripartum cardiomyopathy. The definition of peripartum cardiomyopathy and general issues about diagnosis and pathogenesis of the disorder are provided at the head of the review. Particularly, the role of the system «prolactin — cathepsin D — prolactin 16 kDa» in cardiomyopathy development is disclosed. The general approaches to management of the patients are highlighted. The review provides detailed data about indications, adverse effects and derived clinical experience concerning the main pharmacological drugs which had been used in peripartum cardiomyopathy treatment given their possible unfavorable influence on fetus maturation and maternal lactation. The detailed description is provided on diuretics including loop, thiazide and potassium-sparing drugs. It was noted relative safety and efficiency of nitrates and hydralazine in conditions of limited choice from vasodilator group and, particularly, angiotensinconverting-enzyme inhibitors and angiotensin-II receptor blockers which are contraindicated in pregnancy. A special attention is paid to the group of inotropic drugs: levosimendan, milrinone, and cardiac glycosides. The role of β-blockers and ivabradine is disclosed in heart failure treatment of peripartum cardiomyopathy. Anticoagulants were presented in details given that these drugs are justified in severe cardiac chambers dilation, decrease in ejection fraction, and in presence of intracardiac thrombosis. The place of antiarrhythmic drugs administrating in various cardiac rhythm disorders is discussed in the review. The data is given with account of potential influence on fetus in antenatal peripartum cardiomyopathy in which lidocaine and sotalol are the most preferable drugs; adenosine, quinidine, and flecainide are useful with caution, but amiodarone and dronedarone are absolutely contraindicated. Taking into account proposed pathogenic

  5. Clinical study of electrophysiological changes of optic nerves in early period of type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Quan-Liang Zhao

    2016-07-01

    Full Text Available AIM:To investigate the value of pattern visual evoked potential(PVEPand flash electroretinogram(FERGin early diagnosis and prevention of diabetic retinopathy(DR, analyzing the correlation of early stage DR with PVEP and FERG.METHODS:Sixty patients, 30 males and 30 females, participated in observation group. Their average age was 19.42±7.78years. The duration of DM was RESULTS:In observation group, P100 amplitude decreased and P100 latency increased, compared to those of control group(PPCONCLUSION: PVEP are sensitive to optic neuron damage; FERG is desirable to detect the lesion of Müller cells and bipolar cells. P100 amplitude by PVEP, b-wave amplitude by FERG may be the most sensitive parameter for DR at early stage.

  6. Randomized efficacy trial of early preconception counseling for diabetic teens (READY-girls).

    Science.gov (United States)

    Charron-Prochownik, Denise; Ferons-Hannan, Margaret; Sereika, Susan; Becker, Dorothy

    2008-07-01

    To develop and assess the feasibility of an early preconception counseling program for adolescents called READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls). A total of 53 adolescent females with type 1 diabetes between 16 and 19.9 years of age were randomized into groups receiving a CD-ROM, a book, or standard care (control) and given one comprehensive session. Outcomes were assessed at baseline, immediately after, and at 3 months. Teens who received the CD and those who received the book demonstrated significant (P Future studies should examine repeated boosters of a CD and a book, which are not meant to replace but rather to reinforce and supplement health professional education.

  7. Evaluation of determining serum α1-microglobulin level for early diagnosis of the diabetic retinopathy

    International Nuclear Information System (INIS)

    Jiang Quanxin; Han Laixin; Yin Shihua; Meng Lingqiang

    1995-01-01

    The serum α 1 -MG, β 2 -MG and other indices of 35 patients with NIDDM and 15 patients with diabetic retinopathy are determined. The results show that not only the serum α 1 -MG, β 2 -MG of all patients are obviously higher than the normal, but the serum α 1 -MG rises earlier than β 2 -MG. By means of correlation analysis, the serum β 2 -MG is significantly correlative with β 2 -MG and Scr(r = 0.673, r = 0.608). All those indicate that the level of the serum α 1 -MG may be a reliable and sensitive index to the diabetic retinopathy in the early diagnosis

  8. Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

    Science.gov (United States)

    Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

    2016-01-01

    Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

  9. Netrin-1, a urinary proximal tubular injury marker, is elevated early in the time course of human diabetes

    NARCIS (Netherlands)

    Jayakumar, Calpurnia; Nauta, Ferdau L.; Bakker, Stephan J. L.; Bilo, Henk; Gansevoort, Ron T.; Johnson, Maribeth H.; Ramesh, Ganesan

    Netrin-1 was recently identified as an early diagnostic biomarker of chronic kidney disease (CKD) in an experimental animal model. However, its usefulness for early diagnosis of CKD in humans is unknown. The current study evaluated whether netrin-1 is increased in urine from human diabetic patients.

  10. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

  11. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

    2011-01-01

    The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting that preecla......The vasoactive markers of cardiac overload Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP) are elevated in preeclampsia. This study documents higher ANP concentrations as early as at 9 weeks in type 1 diabetic women subsequently developing preeclampsia suggesting...... that preeclampsia is associated with cardiovascular changes in early pregnancy....

  12. Clinical features of Noncompaction Cardiomyopathy

    NARCIS (Netherlands)

    K. Caliskan (Kadir)

    2012-01-01

    textabstractNoncompaction cardiomyopathy (NCCM) is recognized as a separate disease entity since the first report in 1984 of a rare case with persistent myocardial sinusoids and a series of 8 pediatric and adolescent patients in 1990 with increased trabeculation of the left ventricular endocardium.

  13. New insights into cirrhotic cardiomyopathy

    DEFF Research Database (Denmark)

    Møller, Søren; Hove, Jens D; Dixen, Ulrik

    2013-01-01

    beta-receptor function seem involved in the autonomic and cardiac dysfunction. Cirrhotic cardiomyopathy can be revealed by tissue Doppler imaging but is best demasked by physical or pharmacological stress. Liver transplantation may revert cardiac dysfunction but surgery and shunt insertion may also...

  14. Early screening for type 2 diabetes following gestational diabetes mellitus in France: hardly any impact of the 2010 guidelines.

    Science.gov (United States)

    Goueslard, K; Cottenet, J; Mariet, A-S; Sagot, P; Petit, J-M; Quantin, C

    2017-07-01

    Women who had gestational diabetes mellitus (GDM) have a high risk of type 2 diabetes mellitus (T2DM) in the years following pregnancy. Most follow-up screening studies have been conducted in limited geographical areas leading to large variability in the results. The aim of our investigation was to measure how the publication of guidelines affected early screening for T2DM after a pregnancy with GDM during the period 2007-2013, in France. We conducted a retrospective cohort study in a representative sample of 1/97th of the French population using data from the "National Health Insurance Inter-Regime Information System," which collects individual hospital and non-hospital data for healthcare consumption. The sample included 49,080 women who gave birth in 2007-2013. In the following 3 months, only 18.49% of women with GDM had an oral glucose tolerance test or a blood glucose test in 2007. This rate had not significantly increased in 2013 (p = 0.18). The proportion of women with GDM who had the recommended glycemic follow-up at 3 months (20.30 vs. 21.58%, p = 0.19) and 6 months (32.48 vs. 37.16%, p = 0.08) was not significantly different before the guidelines (2008-2009) and after the guidelines (2012-2013). At 12 months, the difference was significant (46.77 vs. 54.05%, p = 0.009). Postpartum screening has improved only slightly since the guidelines and remains largely insufficient, with less than 25% of women with GDM screened in the first 3 months. In the first year after delivery, less than 60% of women were screened for T2DM.

  15. Ameliorative effect of dietary genistein on diabetes induced hyper-inflammation and oxidative stress during early stage of wound healing in alloxan induced diabetic mice.

    Science.gov (United States)

    Eo, Hyeyoon; Lee, Hea-Ji; Lim, Yunsook

    2016-09-23

    Among the diabetic complications, diabetic foot ulcer due to delayed wound healing is one of the most significant clinical problems. Early inflammatory stage is important for better prognosis during wound healing. Thus, regulation of inflammatory response during early stage of wound healing is main target for complete cutaneous recovery. This study investigated the role of genistein supplementation in inflammation and oxidative stress, which are related to NLRP3 inflammasome, NFκB and Nrf2 activation, during cutaneous wound healing in alloxan-induced diabetic mice. Mice with diabetes with fasting blood glucose (FBG) levels > 250 mg/dl were fed diets with AIN-93G rodent diet containing 0%, 0.025% (LG) or 0.1% (HG) genistein. After 2 weeks of genistein supplementation, excisional wounds were made by biopsy punches (4 mm). Genistein supplementation improved fasting glucose levels and wound closure rate. Moreover, genistein supplementation restored NLRP3 inflammasome (NLRP3, ASC and caspase-1) at the basal level and ameliorated both inflammation (TNFα, iNOS, COX2 and NFκB) and antioxidant defense system (Nrf2, HO-1, GPx, and catalase) during early stage of wound healing in diabetic mice. Taken together, genistein supplementation would be a potential therapeutic nutrient in prevention and treatment of delayed wound healing by modulation of inflammation and oxidative stress during inflammatory stage. Copyright © 2016. Published by Elsevier Inc.

  16. Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

    Science.gov (United States)

    Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia

    2017-01-01

    The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort. Copyright © 2017 by the Endocrine Society

  17. Living with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Subasic, Kim

    2013-12-01

    The purpose of this study is to provide an insider's account of what it is like to live with hypertrophic cardiomyopathy (HCM), a genetic cardiovascular illness that carries the risk for sudden cardiac death. This study aims to reveal how HCM impacts the family and guides the decision whether or not to pursue genetic testing, how the physical limitations associated with HCM alter being-in-the-world, and how HCM alters social relationships. Fifteen adults with HCM were recruited for a longitudinal, phenomenological, qualitative study through purposive sampling and word of mouth. A total of 45 interviews were conducted by the researcher at a time and place designated by the participant between August 2011 and January 2012. The first interview with each participant was conducted in person. While efforts were made to conduct all interviews in person, a total of three interviews were conducted by telephone as requested by three participants due to scheduling conflicts. Through methods of interpretive phenomenology, three audio-recorded, semistructured interviews occurred over the course of 3 months. Detailed narratives were solicited and transcribed verbatim. Methodological and analytical documentation was supported with the identification of key phrases, similar experiences, themes, and documentation of the rationale for decisions throughout the research process. Participation in genetic testing carries a multitude of personal, familial, financial, and emotional implications. The results of a genetic test elicited an emotional response regardless of whether the results were negative, positive, or inconclusive. Living with a potentially life-threatening illness altered identity, disrupted social relationships, and generated chronic fear and uncertainty. A new normal was re-ordered or transformed by the demands and limitations posed by HCM, and by the person's concerns, priorities, and the meaning of the illness. Results from this study underscore the need for healthcare

  18. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

    Science.gov (United States)

    Vujosevic, Stela; Bottega, Elisa; Casciano, Margherita; Pilotto, Elisabetta; Convento, Enrica; Midena, Edoardo

    2010-06-01

    The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema.

  19. Noninvasive and invasive evaluation of cardiac dysfunction in experimental diabetes in rodents

    Directory of Open Access Journals (Sweden)

    Salemi Vera

    2007-04-01

    Full Text Available Abstract Background Because cardiomyopathy is the leading cause of death in diabetic patients, the determination of myocardial function in diabetes mellitus is essential. In the present study, we provide an integrated approach, using noninvasive echocardiography and invasive hemodynamics to assess early changes in myocardial function of diabetic rats. Methods Diabetes was induced by streptozotocin injection (STZ, 50 mg/kg. After 30 days, echocardiography (noninvasive at rest and invasive left ventricular (LV cannulation at rest, during and after volume overload, were performed in diabetic (D, N = 7 and control rats (C, N = 7. The Student t test was performed to compare metabolic and echocardiographic differences between groups at 30 days. ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P Results Diabetes impaired LV systolic function expressed by reduced fractional shortening, ejection fraction, and velocity of circumferential fiber shortening compared with that in the control group. The diabetic LV diastolic dysfunction was evidenced by diminished E-waves and increased A-waves and isovolumic relaxation time. The myocardial performance index was greater in diabetic compared with control rats, indicating impairment in diastolic and systolic function. The LV systolic pressure was reduced and the LV end-diastolic pressure was increased at rest in diabetic rats. The volume overload increased LVEDP in both groups, while LVEDP remained increased after volume overload only in diabetic rats. Conclusion These results suggest that STZ-diabetes induces systolic and diastolic dysfunction at rest, and reduces the capacity for cardiac adjustment to volume overload. In addition, it was also demonstrated that rodent echocardiography can be a useful, clinically relevant tool for the study of initial diabetic cardiomyopathy manifestations in asymptomatic patients.

  20. Clinical Features and Echocardiographic Findings in Children with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristina Blesneac

    2013-12-01

    Full Text Available Background: Hypertrophic cardiomyopathy, one of the most common inherited cardiomyopathies, is a heterogeneous disease resulting from sarcomeric protein mutations, with an incidence in the adult population of 1:500. Current information on the epidemiology and outcomes of this disease in children is limited. Methods: Thirty-four children diagnosed with hypertrophic cardiomyopathy in the Pediatric Cardiology Department from Tîrgu Mureș were evaluated concerning familial and personal history, clinical, paraclinical and therapeutic aspects. Hypertrophic cardiomyopathy was defined by the presence of a hypertrophied, non-dilated ventricle, in the absence of a cardiac or systemic disease that could produce ventricular hypertrophy. Results: The youngest diagnosed child was a neonate, a total of 10 patients being diagnosed until 1 year of age. In 6 cases a positive familial history was found. Noonan syndrome was found in 2 cases. Only 21 patients were symptomatic, the predominant symptoms being shortness of breath on exertion with exercise limitations. Left ventricular outflow tract obstruction was present in 21 cases (61.7%. Twenty-four patients were on β-blocking therapy, while 4 patients underwent septal myectomy. Conclusions: Hypertrophic cardiomyopathy is a heterogeneous disorder in terms of evolution, age of onset, type and extent of hypertrophy, and the risk of sudden death. It can affect children of any age. There is a need for a complex evaluation, including familial and personal anamnesis, clinical examination, electrocardiogram and echocardiography of all patients. It is highly important to develop screening strategies, including genetic testing, for an early diagnosis, especially in asymptomatic patients with a positive familial background

  1. Use of Chlorothiazide in the Management of Central Diabetes Insipidus in Early Infancy

    Directory of Open Access Journals (Sweden)

    Manish Raisingani

    2017-01-01

    Full Text Available Management of central diabetes insipidus in infancy is challenging. The various forms of desmopressin, oral, subcutaneous, and intranasal, have variability in the duration of action. Infants consume most of their calories as liquids which with desmopressin puts them at risk for hyponatremia and seizures. There are few cases reporting chlorothiazide as a temporizing measure for central diabetes insipidus in infancy. A male infant presented on day of life 30 with holoprosencephaly, cleft lip and palate, and poor weight gain to endocrine clinic. Biochemical tests and urine output were consistent with central diabetes insipidus. The patient required approximately 2.5 times the normal fluid intake to keep up with the urine output. Patient was started on low renal solute load formula and oral chlorothiazide. There were normalization of serum sodium, decrease in fluid intake close to 1.3 times the normal, and improved urine output. There were no episodes of hyponatremia/hypernatremia inpatient. The patient had 2 episodes of hypernatremia in the first year of life resolving with few hours of hydration. Oral chlorothiazide is a potential bridging agent for treatment of central DI along with low renal solute load formula in early infancy. It can help achieve adequate control of DI without wide serum sodium fluctuations.

  2. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

    DEFF Research Database (Denmark)

    Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio

    2014-01-01

    AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed...... the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

  3. AMA0428, A Potent Rock Inhibitor, Attenuates Early and Late Experimental Diabetic Retinopathy.

    Science.gov (United States)

    Hollanders, Karolien; Hove, Inge Van; Sergeys, Jurgen; Bergen, Tine Van; Lefevere, Evy; Kindt, Nele; Castermans, Karolien; Vandewalle, Evelien; van Pelt, Jos; Moons, Lieve; Stalmans, Ingeborg

    2017-02-01

    Diabetic retinopathy (DR) is characterized by an early stage of inflammation and vessel leakage, and an advanced vasoproliferative stage. Also, neurodegeneration might play an important role in disease pathogenesis. The aim of this study was to investigate the effect of the Rho kinase (ROCK) inhibitor, AMA0428, on these processes. The response to ROCK inhibition by AMA0428 (1 µg) was studied in vivo using the murine model for streptozotocin (STZ)-induced diabetes, focusing on early non-proliferative DR features and the oxygen-induced retinopathy (OIR) model to investigate proliferative DR. Intravitreal (IVT) administration of AMA0428 was compared with murine anti-VEGF-R2 antibody (DC101, 6.2 µg) and placebo (H 2 O/PEG; 1C8). Outcome was assessed by analyzing leukostasis using fluorescein isothiocyanate coupled concanavalin A (FITC-ConA) and vessel leakage (bovine serum albumin conjugated with fluorescein isothiocyanate; FITC-BSA)/neovascularization and neurodegeneration by immunohistological approaches (hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL), Brn3a). ELISA and Western blotting were employed to unravel the consequences of ROCK inhibition (1 µM AMA0428) on myosin phosphatase target protein (MYPT)-1 phosphorylation, endothelial nitric oxide synthase (eNOS) phosphorylation, and vascular endothelial growth factor (VEGF) levels in retinas of diabetic mice, on NF-κβ activity and ICAM-1 expression in endothelial cells (ECs). In vivo, AMA0428 significantly reduced vessel leakage and neovascularization, respectively, in the STZ and OIR model, comparable to DC101 therapy. Additionally, the ROCK inhibitor decreased neurodegeneration in both models and inhibited leukostasis by 30% (p diabetic retina and AMA0428 administration resulted in decreased phospho-MYPT-1, enhanced phospho-eNOS, and reduced VEGF levels. In vitro, AMA0428 interfered with NF-κβ activity, thereby inhibiting ICAM-1

  4. Risk of Cardiomyopathy in Younger Persons With a Family History of Death from Cardiomyopathy

    DEFF Research Database (Denmark)

    Ranthe, Mattis F; Carstensen, Lisbeth; Øyen, Nina

    2015-01-01

    at the population level is unclear. In a nationwide cohort, we examined the risk of cardiomyopathy by family history of premature death (... ascertained family history of premature (... incidence rate ratios for cardiomyopathy by family history of premature death. Premature cardiomyopathy deaths in first- and second-degree relatives were associated with 29- and 6-fold increases in the rate of cardiomyopathy, respectively. If the first-degree relative died aged

  5. Intensity of early correction of hyperglycaemia and outcome of critically ill patients with diabetic ketoacidosis.

    Science.gov (United States)

    Mårtensson, Johan; Bailey, Michael; Venkatesh, Balasubramanian; Pilcher, David; Deane, Adam; Abdelhamid, Yasmine Ali; Crisman, Marco; Verma, Brij; MacIsaac, Christopher; Wigmore, Geoffrey; Shehabi, Yahya; Suzuki, Takafumi; French, Craig; Orford, Neil; Kakho, Nima; Prins, Johannes; Ekinci, Elif I; Bellomo, Rinaldo

    2017-09-01

    To determine the impact of the intensity of early correction of hyperglycaemia on outcomes in patients with diabetic ketoacidosis (DKA) admitted to the intensive care unit. We studied adult patients with DKA admitted to 171 ICUs in Australia and New Zealand from 2000 to 2013. We used their blood glucose levels (BGLs) in the first 24 hours after ICU admission to determine whether intensive early correction of hyperglycemia to ≤ 180 mg/dL was independently associated with hypoglycaemia, hypokalaemia, hypo-osmolarity or mortality, compared with partial early correction to > 180 mg/dL as recommended by DKA-specific guidelines. Among 8553 patients, intensive early correction of BGL was applied to 605 patients (7.1%). A greater proportion of these patients experienced hypoglycaemia (20.2% v 9.1%; P < 0.001) and/or hypo-osmolarity (29.4% v 22.0%; P < 0.001), but not hypokalaemia (16.7% v 15.6%; P = 0.47). Overall, 11 patients (1.8%) in the intensive correction group and 112 patients (1.4%) in the partial correction group died (P = 0.42). However, after adjustment for illness severity, partial early correction of BGL was independently associated with a lower risk of hypoglycaemia (odds ratio [OR], 0.38; 95% CI, 0.30-0.48; P < 0.001), lower risk of hypo-osmolarity (OR, 0.80; 95% CI, 0.65-0.98; P < 0.03) and lower risk of death (OR, 0.44; 95% CI, 0.22-0.86; P = 0.02). In a large cohort of patients with DKA, partial early correction of BGL according to DKA-specific guidelines, when compared with intensive early correction of BGL, was independently associated with a lower risk of hypoglycaemia, hypo-osmolarity and death.

  6. Hepatocyte nuclear factor 1-alpha mutation in normal glucose-tolerant subjects and early-onset type 2 diabetic patients

    OpenAIRE

    Lim, Dong Mee; Huh, Nam; Park, Keun Yong

    2008-01-01

    Background/Aims The prevalence of diabetes in Korea is reported to be approximately 10%, but cases of maturity-onset diabetes of the young (MODY) are rare in Korea. A diagnostic technique for autosomal dominant MODY is being actively sought. In this regard, we used a DNA chip to investigate the frequency of mutations of the MODY3 gene (hepatocyte nuclear factor-1?) in Korean patients with early-onset type 2 diabetes. Methods The genomic DNA of 30 normal individuals [age, 24.9?8.6 years] and 2...

  7. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis.

    Science.gov (United States)

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-09-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P<0.01), compared to normal controls. More than 80% of the VEGFR-2 in the diabetic retina was in the capillaries, compared to 47% in normal controls (P<0.01). Angiography in rabbit retinas revealed microvascular capillaries to be the location for VEGF-A-induced leakage, as expressed by significantly higher rate of fluorophore spreading with VEGF-A injection when compared to vehicle control (26±2 vs. 3±1 μm/s, P<0.05). Immunohistochemistry showed VEGFR-2 expression in capillaries of diabetic animals but not in normal controls. Macular vessels from diabetic patients (n=7) showed significantly more VEGFR-2 compared to nondiabetic controls (n=5) or peripheral retinal regions of the same retinas (P<0.01 in both cases). Here we introduce a new approach for early diagnosis of DR and VEGFR-2 as a molecular marker. VEGFR-2 could become a key diagnostic target, one that might help to prevent retinal vascular leakage and proliferation in diabetic patients. © FASEB.

  8. Risk of Vaginal Infections at Early Gestation in Patients with Diabetic Conditions during Pregnancy: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Julian Marschalek

    Full Text Available Pregnant women with gestational diabetes mellitus (GDM are reported to be at increased risk for infections of the genital tract. This study aimed to compare the prevalence of asymptomatic bacterial vaginosis (BV and Candida colonization at early gestation between pregnant women with and without diabetic conditions during pregnancy. We included data from 8, 486 singleton pregnancies that underwent an antenatal infection screen-and-treat programme at our department. All women with GDM or pre-existing diabetes were retrospectively assigned to the diabetic group (DIAB, whereas non-diabetic women served as controls (CON. Prevalence for BV and Candida colonization was 9% and 14% in the DIAB group, and 9% and 13% in the CON group, respectively (n.s.. No significant difference regarding stillbirth and preterm delivery (PTD, defined as a delivery earlier than 37 + 0 (37 weeks plus 0 days weeks of gestation was found. We could not find an increased risk of colonization with vaginal pathogens at early gestation in pregnant women with diabetes, compared to non-diabetic women. Large prospective studies are needed to evaluate the long-term risk of colonization with vaginal pathogens during the course of pregnancy in these women.

  9. Role of cardiac MRI in nonischemic cardiomyopathies.

    Science.gov (United States)

    Anand, Senthil; Janardhanan, Rajesh

    2016-01-01

    Cardiac magnetic resonance (CMR) with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies. Published by Elsevier B.V.

  10. Role of cardiac MRI in nonischemic cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Senthil Anand

    2016-05-01

    Full Text Available Cardiac magnetic resonance (CMR with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies.

  11. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy and infiltrative cardiomyopathy

    OpenAIRE

    Schofield, Rebecca; Manacho, Katia; Castelletti, Silvia; Moon, James C.

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Cardiac imaging plays a key role in the diagnosis and management, with cardiovascular magnetic resonance (CMR) an important modality. CMR provides a number of different techniques in one examination: structure and function, flow imaging and tissue characterisation particularly with the late gadolinium enhancement (LGE) technique. Other techniques include vasodilator perfusion, mapping (especially T1 mapping and ex...

  12. Early-Life Nutritional Programming of Type 2 Diabetes: Experimental and Quasi-Experimental Evidence.

    Science.gov (United States)

    Vaiserman, Alexander M

    2017-03-05

    Consistent evidence from both experimental and human studies suggest that inadequate nutrition in early life can contribute to risk of developing metabolic disorders including type 2 diabetes (T2D) in adult life. In human populations, most findings supporting a causative relationship between early-life malnutrition and subsequent risk of T2D were obtained from quasi-experimental studies ('natural experiments'). Prenatal and/or early postnatal exposures to famine were demonstrated to be associated with higher risk of T2D in many cohorts around the world. Recent studies have highlighted the importance of epigenetic regulation of gene expression as a possible major contributor to the link between the early-life famine exposure and T2D in adulthood. Findings from these studies suggest that prenatal exposure to the famine may result in induction of persistent epigenetic changes that have adaptive significance in postnatal development but can predispose to metabolic disorders including T2D at the late stages of life. In this review, quasi-experimental data on the developmental programming of T2D are summarized and recent research findings on changes in DNA methylation that mediate these effects are discussed.

  13. Altered retinal microRNA expression profiles in early diabetic retinopathy: an in silico analysis.

    Science.gov (United States)

    Xiong, Fen; Du, Xinhua; Hu, Jianyan; Li, Tingting; Du, Shanshan; Wu, Qiang

    2014-07-01

    MicroRNAs (miRNAs) - as negative regulators of target genes - are associated with various human diseases, but their precise role(s) in diabetic retinopathy (DR) remains to be elucidated. The aim of this study was to elucidate the involvement of miRNAs in early DR using in silico analysis to explore their gene expression patterns. We used the streptozotocin (STZ)-induced diabetic rat to investigate the roles of miRNAs in early DR. Retinal miRNA expression profiles from diabetic versus healthy control rats were examined by miRNA array analysis. Based on several bioinformatic systems, specifically, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified signatures of the potential pathological processes, gene functions, and signaling pathways that are influenced by dysregulated miRNAs. We used quantitative real-time polymerase chain reaction (qRT-PCR) to validate six (i.e. those with significant changes in expression levels) of the 17 miRNAs that were detected in the miRNA array. We also describe the significant role of the miRNA-gene network, which is based on the interactions between miRNAs and target genes. GO analysis of the 17 miRNAs detected in the miRNA array analysis revealed the most prevalent miRNAs to be those related to biological processes, olfactory bulb development and axonogenesis. These miRNAs also exert significant influence on additional pathways, including the mitogen-activated protein and calcium signaling pathways. Six of the seventeen miRNAs were chosen for qRT-PCR validation. With the exception of a slight difference in miRNA-350, our results are in close agreement with the differential expressions detected by array analysis. This study, which describes miRNA expression during the early developmental phases of DR, revealed extensive miRNA interactions. Based on both their target genes and signaling pathways, we suggest that miRNAs perform critical regulatory functions during the early stages of DR

  14. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio

    2000-01-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  15. Correlation between Retinal Vessel Calibre and Neurodegeneration in Patients with Type 2 Diabetes Mellitus in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR)

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Simó, Rafael

    2016-01-01

    .04). In a multivariable linear regression model, CRAE was associated with macular ganglion cell layer thickness (coefficient 0.27 per micrometre, p correlated with macular retinal thickness (coefficient -0.07 per micrometre, p = 0.04) and retinal nerve fibre layer thickness at the optic disc......PURPOSE: To investigate the correlation between retinal vessel calibre and measurements of neurodegeneration in patients with type 2 diabetes (T2D) and no or early diabetic retinopathy (DR). METHODS: Baseline data on 440 patients with T2D from the EUROCONDOR clinical trial were used. DR was graded...... (coefficient 0.32 per micrometre, p

  16. Cardiovascular disease, diabetes and early exit from paid employment in Europe; the impact of work-related factors.

    Science.gov (United States)

    Kouwenhoven-Pasmooij, T A; Burdorf, A; Roos-Hesselink, J W; Hunink, M G M; Robroek, S J W

    2016-07-15

    The aims of the study were to examine (i) the association between cardiovascular disease (CVD) or diabetes and exit from paid employment via disability benefits, unemployment, early retirement or other exit routes; and (ii) the impact of work-related factors on exit from paid employment among individuals with CVD or diabetes. Respondents of the longitudinal Survey of Health and Retirement in Europe (SHARE) were included if they were aged >50years, had paid employment at baseline, and a known employment status after 2 or 6years (n=5182). A baseline-interview provided information on the presence of diagnosed CVD and diabetes, and physical and psychosocial work-related factors. During follow-up interviews information on work status was collected. Multinomial regression analyses were used to investigate the association between CVD, diabetes and exit from paid employment, and the impact of work-related factors. Workers with CVD or diabetes had significantly increased probabilities of disability benefits (OR 2.50, 95% CI 1.69-3.70) and early retirement (OR 1.34, 95% CI 1.05-1.74), but a comparable probability of unemployment (OR 1.10, 95% CI 0.71-1.71). Regarding disability benefits, individuals who had a stroke had the highest probability (OR 3.48, 95% CI 1.31-9.23). Perceived high job demands with low rewards or with low control at work further increased the probability of early exit among individuals with CVD or diabetes. Our study shows a prominent role of CVD and diabetes in premature losses to the workforce, and it shows that optimizing psychosocial work-related factors could be beneficial in people with CVD or diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

    Science.gov (United States)

    Yogasundaram, Haran; Putko, Brendan N; Tien, Julia; Paterson, D Ian; Cujec, Bibiana; Ringrose, Jennifer; Oudit, Gavin Y

    2014-12-01

    Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine. Retinal toxicity, neuromyopathy, and cardiac disease are recognized adverse effects of hydroxychloroquine. Immediate withdrawal of hydroxychloroquine is essential if toxicity is suspected because of the early reversibility of cardiomyopathy. In addition to recommended ophthalmological screening, regular screening with 12-lead electrocardiogram and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients. Cardiac magnetic resonance imaging and endomyocardial biopsy are valuable tools to provide prognostic insights and confirm the diagnosis of hydroxychloroquine-induced cardiomyopathy. In conclusion, chronic use of hydroxychloroquine can result in an acquired lysosomal storage disorder, leading to a drug-induced cardiomyopathy characterized by concentric hypertrophy and conduction abnormalities associated with increased adverse clinical outcomes and mortality. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  18. Peripartum Cardiomyopathy Presenting as Bradycardia

    OpenAIRE

    Codsi, Elisabeth; Rose, Carl H.; Tweet, Marysia S.; Hayes, Sharonne N.; Best, Patricia J. M.; Blauwet, Lori A.

    2017-01-01

    Peripartum cardiomyopathy (PPCM) is a disease that typically affects young otherwise healthy women. As PPCM is associated with significant mortality, timely diagnosis is necessary to ensure appropriate care. To our knowledge, this represents the first reported case of PPCM presenting as symptomatic bradycardia. We describe the patient’s clinical presentation and relevant findings and review the potential etiology and ramifications of bradycardia in patients with PPCM.

  19. Maternal TSH level and TPOAb status in early pregnancy and their relationship to the risk of gestational diabetes mellitus.

    Science.gov (United States)

    Ying, Hao; Tang, Yu-Ping; Bao, Yi-Rong; Su, Xiu-Juan; Cai, XueYa; Li, Yu-Hong; Wang, De-Fen

    2016-12-01

    Subclinical hypothyroidism is common in pregnant women and often related to adverse pregnancy outcomes, but its relationship with gestational diabetes remains controversial. In particular, the impact of thyroperoxidase antibodies status on the relationship between subclinical hypothyroidism and gestational diabetes is not clear. We investigated the association between combined thyroid stimulating hormone (TSH) level and thyroperoxidase antibodies status in early pregnancy (gestation) and gestational diabetes mellitus. A total of 7084 pregnant women met the inclusion criteria, which included thyroperoxidase antibodies-positive subclinical hypothyroidism [TSH(H)TPOAb(+)] (n = 78), thyroperoxidase antibodies-negative subclinical hypothyroidism [TSH(H)TPOAb(-)] (n = 281), thyroperoxidase antibodies-positive euthyroidism [TSH(N)TPOAb(+)] (n = 648), and thyroperoxidase antibodies-negative euthyroidism [TSH(N)TPOAb(-)] (n = 6077). Of the 7084 cases included in our study, 1141 cases were diagnosed with gestational diabetes mellitus at 24-28 weeks of pregnancy. The prevalence of gestational diabetes mellitus in TSH(N)TPOAb(-), TSH(H)TPOAb(-), TSH(N)TPOAb(+), and TSH(H)TPOAb(+) was 14.65, 19.57, 24.85, and 46.15 %, respectively. Compared with TSH(N)TPOAb(-) women, the risk of gestational diabetes mellitus was increased in all other groups of women in early pregnancy. After dividing early pregnancy into first and second trimesters, we found that TSH(H)TPOAb(-) women in the first trimester do not show this increase. Our study suggests that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism in early pregnancy are associated with an increased risk of gestational diabetes mellitus.

  20. Determinants of Thyrotoxic Cardiomyopathy Recovery

    Directory of Open Access Journals (Sweden)

    Lucia Oliveros-Ruiz

    2013-01-01

    Full Text Available The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment.

  1. Genetic basis of arrhythmogenic cardiomyopathy.

    Science.gov (United States)

    Karmouch, Jennifer; Protonotarios, Alexandros; Syrris, Petros

    2018-05-01

    To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM. Use of next-generation sequencing methods has resulted in the identification of novel causative variants and genes for ACM. The involvement of filamin C in ACM demonstrates the genetic overlap between ACM and other types of cardiomyopathy. Putative pathogenic variants have been detected in cadherin 2 gene, a protein involved in cell adhesion. Large genomic rearrangements in desmosome genes have been systematically investigated in a cohort of ACM patients. Recent studies have identified novel causes of ACM providing new insights into the genetic spectrum of the disease and highlighting an overlapping phenotype between ACM and dilated cardiomyopathy. Next-generation sequencing is a useful tool for research and genetic diagnostic screening but interpretation of identified sequence variants requires caution and should be performed in specialized centres.

  2. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Science.gov (United States)

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

    2014-01-01

    In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

  3. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Bai

    Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

  4. [Surgical revascularisation of the heart in patients with chronic ischaemic cardiomyopathy and leftventricular ejection fraction of less than 30%].

    Science.gov (United States)

    Velinović, Milos; Kocica, Mladen; Vranes, Mile; Mikić, Aleksandar; Vukomanović, Vlada; Davidović, Lazar; Obrenović-Krićanski, Biljana; Cvetkovic, Slobodan; Soski, Ljiljana; Ristić, Arsen D

    2005-01-01

    Patients suffering from chronic ischaemic cardiomyopathy and left ventricular ejection fraction (LVEF) lower than 30% represent a difficult and controversial population for surgical treatment. The aim of this study was to evaluate the effects of surgical treatment on the early and long-term outcome of these patients. The patient population comprised 50 patients with LVEF < 30% (78% male, mean age: 58.3 years, range: 42-75 years) who underwent surgical myocardial revascularisation during the period 1995-2000. Patients with left ventricular aneurysms or mitral valve insufficiency were excluded from the study. The following echocardiography parameters were evaluated as possible prognostic indicators: LVEF, fraction of shortening (FS), left ventricular systolic and diastolic diameters (LVEDD, LVESD) and volumes (LVEDV, LVESV), as well as their indexed values (LVESVI). Fifteen patients (30%) died during the follow-up, 2/50 intraoperatively (4%). The presence of diabetes mellitus, previous myocardial infarction, main left coronary artery disease, and three-vessel disease, correlated significantly with the surgical outcomes. The patient's age, family history, smoking habits, hypertension, hyperlipidaemia, history of stroke, peripheral vascular disease, and renal failure, did not correlate with the mortality rate. A comparison of preoperative echocardiography parameters between survivors and non-survivors revealed significantly divergent LVEF, LVEDD, LVESD, LVEDV, LVESV, and LVESVI values. Preoperative LVESVI offered the highest predictive value (R = 0.595). Diabetes mellitus, history of myocardial infarction, stenosis of the main branch, and three-vessel disease, significantly affected the perioperative and long-term outcome of surgical revascularisation in patients with ischaemic cardiomyopathy and LVEF < 30%. In survivors, LVEF, FS, and systolic and diastolic echocardiography parameters, as well as their indexed values, significantly improved after surgical

  5. [Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

    Science.gov (United States)

    Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

    2012-02-01

    Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

  6. Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

    Science.gov (United States)

    Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

    2016-01-01

    We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P  0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

  7. The Impact of Health Education Intervention for Prevention and Early Detection of Type 2 Diabetes in Women with Gestational Diabetes.

    Science.gov (United States)

    Tawfik, Mirella Youssef

    2017-06-01

    This study aims to investigate the impact of a health belief model (HBM)-based educational intervention on knowledge, beliefs, self-reported practices, gestational and postpartum weight in women with gestational diabetes mellitus (GDM). A cluster randomized controlled trial was performed, with randomization at the level of Primary Health Care centers in three Egyptian cities. Eligible women with GDM were enrolled at 24 weeks pregnancy. The intervention group (n = 103) received health education intervention based on the HBM construct. Control subjects (n = 98) received the usual care. The outcomes measured were: women's knowledge, beliefs, self-reported practices, gestational weight gain (GWG), and postpartum weight retention. Patients were investigated at baseline, at end of pregnancy, and at 6 weeks postpartum. After the intervention, percentages of women who had high knowledge and beliefs scores had significantly increased from less than 50 % to more than 70 % in the intervention group (p < 0.001). More women in the intervention group reported practicing exclusive breast feeding (85.4 %) and screening for T2DM (43.7 %) at 6 weeks postpartum compared to the control group (63.3 and 19.4 % respectively) (p < 0.001). More women with excessive body mass index in the intervention group (65 %) compared to the control group (11.6 %) were meeting recommended GWG (p < 0.001), and postpartum weight (37.7, and 20.3 % respectively) (p < 0.01). This intervention significantly improved knowledge, beliefs, self-reported practices, and gestational and postpartum weight in patients with GDM. Further research is needed for investigating the effectiveness of applying early, multi-phase, and longer intervention.

  8. The Ins2Akita mouse as a model of early retinal complications in diabetes.

    Science.gov (United States)

    Barber, Alistair J; Antonetti, David A; Kern, Timothy S; Reiter, Chad E N; Soans, Rohit S; Krady, J Kyle; Levison, Steven W; Gardner, Thomas W; Bronson, Sarah K

    2005-06-01

    This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results in a single amino acid substitution in the insulin 2 gene that causes misfolding of the insulin protein. The mutation arose and is maintained on the C57BL/6J background. Male mice heterozygous for this mutation have progressive loss of beta-cell function, decreased pancreatic beta-cell density, and significant hyperglycemia, as early as 4 weeks of age. Heterozygous Ins2(Akita) mice were bred to C57BL/6J mice, and male offspring were monitored for hyperglycemia, beginning at 4.5 weeks of age. After 4 to 36 weeks of hyperglycemia, the retinas were analyzed for vascular permeability, vascular lesions, leukostasis, morphologic changes of micro- and macroglia, apoptosis, retinal degeneration, and insulin receptor kinase activity. The mean blood glucose of Ins2(Akita) mice was significantly elevated, whereas the body weight at death was reduced compared with that of control animals. Compared with sibling control mice, the Ins2(Akita) mice had increased retinal vascular permeability after 12 weeks of hyperglycemia (P microglia, but no changes in expression of Muller cell glial fibrillary acidic protein. Increased apoptosis was identified by immunoreactivity for active caspase-3 after 4 weeks of hyperglycemia (P cell bodies in the retinal ganglion cell layer (P retinal complications of diabetes.

  9. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery....... The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  10. Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis

    DEFF Research Database (Denmark)

    Overgaard, Anne Julie; Weir, Jacquelyn M; De Souza, David Peter

    2016-01-01

    as methionine deficits were detected in the pre-type 1 diabetic mice. Additionally higher lysophosphatidylinositol levels and low phosphatidylglycerol levels where novel findings in the pre-type 1 diabetic mice. These observations suggest that metabolomic disturbances precede the onset of T1D.......The early mechanisms regulating progression towards beta cell failure in type 1 diabetes (T1D) are poorly understood, but it is generally acknowledged that genetic and environmental components are involved. The metabolomic phenotype is sensitive to minor variations in both, and accordingly reflects...... changes that may lead to the development of T1D. We used two different extraction methods in combination with both liquid- and gas chromatographic techniques coupled to mass spectrometry to profile the metabolites in a transgenic non-diabetes prone C57BL/6 mouse expressing CD154 under the control...

  11. Detection of early metabolic alterations in the ocular fundus of diabetic patients by time-resolved autofluorescence of endogenous fluorophores

    Science.gov (United States)

    Schweitzer, D.; Klemm, M.; Quick, S.; Deutsch, L.; Jentsch, S.; Hammer, M.; Dawczynski, J.; Kloos, C. H.; Mueller, U. A.

    2011-07-01

    Measurements of time-resolved autofluorescence (FLIM) at the human ocular fundus of diabetic patients permit the detection of early pathologic alterations before signs of diabetic retinopathy are visible. The measurements were performed by the Jena Fluorescence Lifetime Laser Scanner Ophthalmoscope applying time-correlated single photon counting (TCSPC) in two spectral channels (K1: 490-560 nm, K2:560-700ps). The fluorescence was excited by 70 ps pulses (FWHM) at 448 nm. The decay of fluorescence intensity was triple-exponentially approximated. The frequency of amplitudes, lifetimes, and relative contributions was compared in fields of the same size and position in healthy subjects and in diabetic patients. The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina. The changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.

  12. Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Lindhardt, Morten; Rossing, Peter

    2016-01-01

    Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can...... prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis......-cause mortality(p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria....

  13. VEGF as a Survival Factor in Ex Vivo Models of Early Diabetic Retinopathy.

    Science.gov (United States)

    Amato, Rosario; Biagioni, Martina; Cammalleri, Maurizio; Dal Monte, Massimo; Casini, Giovanni

    2016-06-01

    Growing evidence indicates neuroprotection as a therapeutic target in diabetic retinopathy (DR). We tested the hypothesis that VEGF is released and acts as a survival factor in the retina in early DR. Ex vivo mouse retinal explants were exposed to stressors similar to those characterizing DR, that is, high glucose (HG), oxidative stress (OS), or advanced glycation end-products (AGE). Neuroprotection was provided using octreotide (OCT), a somatostatin analog, and pituitary adenylate cyclase activating peptide (PACAP), two well-documented neuroprotectants. Data were obtained with real-time RT-PCR, Western blot, ELISA, and immunohistochemistry. Apoptosis was induced in the retinal explants by HG, OS, or AGE treatments. At the same time, explants also showed increased VEGF expression and release. The data revealed that VEGF is released shortly after exposure of the explants to stressors and before the level of cell death reaches its maximum. Retinal cell apoptosis was inhibited by OCT and PACAP. At the same time, OCT and PACAP also reduced VEGF expression and release. Vascular endothelial growth factor turned out to be a protective factor for the stressed retinal explants, because inhibiting VEGF with a VEGF trap further increased cell death. These data show that protecting retinal neurons from diabetic stress also reduces VEGF expression and release, while inhibiting VEGF leads to exacerbation of apoptosis. These observations suggest that the retina in early DR releases VEGF as a prosurvival factor. Neuroprotective agents may decrease the need of VEGF production by the retina, therefore limiting the risk, in the long term, of pathologic angiogenesis.

  14. Cardiomyopathy in becker muscular dystrophy: Overview.

    Science.gov (United States)

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

  15. Diagnostic work-up in cardiomyopathies

    DEFF Research Database (Denmark)

    Rapezzi, Claudio; Arbustini, Eloisa; Caforio, Alida L P

    2013-01-01

    a framework for the clinical approach to diagnosis in cardiomyopathies based on the recognition of diagnostic 'red flags' that can be used to guide rational selection of specialized tests including genetic analysis. The basic premise is that the adoption of a cardiomyopathy-specific mindset which combines...

  16. Peripartum cardiomyopathy: Euro Observational Research Program

    NARCIS (Netherlands)

    Hoes, M. F.; van Hagen, I.; Russo, F.; van Veldhuisen, D. J.; van den Berg, M. P.; Roos-Hesselink, J.; van Spaendonck-Zwarts, K. Y.; van der Meer, P.

    2014-01-01

    Peripartum cardiomyopathy is a rare but potentially life-threatening form of heart failure affecting women late in pregnancy or in the first months after delivery. Peripartum cardiomyopathy is difficult to diagnose and its onset and progression are variable between individuals. The pathophysiology

  17. Peripartum cardiomyopathy : Euro Observational Research Program

    NARCIS (Netherlands)

    Hoes, M. F.; van Hagen, I.; Russo, F.; Van Veldhuisen, D. J.; Van den Berg, M. P.; Roos-Hesselink, J.; van Spaendonck-Zwarts, K. Y.; van der Meer, P.

    Peripartum cardiomyopathy is a rare but potentially life-threatening form of heart failure affecting women late in pregnancy or in the first months after delivery. Peripartum cardiomyopathy is difficult to diagnose and its onset and progression are variable between individuals. The pathophysiology

  18. Peripartum Cardiomyopathy: Euro Observational Research Program

    NARCIS (Netherlands)

    M.F. Hoes; I.M. van Hagen (Iris); F. Russo; D.J. van Veldhuisen (Dirk); M.P. van den Berg (Maarten); J.W. Roos-Hesselink (Jolien); K.Y. van Spaendonck-Zwarts (Karin); P. van der Meer (Peter)

    2014-01-01

    textabstractPeripartum cardiomyopathy is a rare but potentially life-threatening form of heart failure affecting women late in pregnancy or in the first months after delivery. Peripartum cardiomyopathy is difficult to diagnose and its onset and progression are variable between individuals. The

  19. Comparison of digital color fundus imaging and fluorescein angiographic findings for the early detection of diabetic retinopathy in young type 1 diabetic patients.

    Science.gov (United States)

    Kapsala, Z; Anastasakis, A; Mamoulakis, D; Maniadaki, I; Tsilimbaris, M

    2018-01-01

    To compare the findings from digital 7-field color fundus (CF) photography and fundus fluorescein angiography (FFA) in young patients with diabetes mellitus (DM) type 1 without known diabetic retinopathy. In this prospective, observational cohort study, 54 type 1 diabetic patients were recruited. Participants had been diagnosed with diabetes mellitus (DM) for at least 6 years, had Best Corrected Visual Acuity of 20/25 or better and did not have any known retinal pathology. One hundred and seven eyes were analyzed. All patients underwent a complete ophthalmic examination in the Retina Service of a University Eye Clinic including digital CF imaging and FFA. The mean age of the patients was 18.6 years. Mean duration of DM was 11.3 years, and mean haemoglobin A1c (HbA1c) level was 8.6%. Of the 107 eyes, 8 eyes (7.5%) showed microvascular abnormalities on CF images, while FFA images revealed changes in 26 eyes (24.3%). Hence, 18 of the 26 eyes showing abnormalities on FFA did not show any abnormalities on CF images. Mean DM duration in the patient group with detectable microvascular changes was found to be significantly higher compared to patients without changes, while no difference in HbA1c levels, serum lipid levels or blood pressure was observed. Comparison of digital CF and FFA findings for the detection of diabetic microvascular changes in type 1 diabetic patients showed that FFA reveals more information about retinal vascular pathology for early detection of diabetic retinopathy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic β-Cell Dysfunction.

    Science.gov (United States)

    Batchuluun, Battsetseg; Al Rijjal, Dana; Prentice, Kacey J; Eversley, Judith A; Burdett, Elena; Mohan, Haneesha; Bhattacharjee, Alpana; Gunderson, Erica P; Liu, Ying; Wheeler, Michael B

    2018-05-01

    Specific circulating metabolites have emerged as important risk factors for the development of diabetes. The acylcarnitines (acylCs) are a family of metabolites known to be elevated in type 2 diabetes (T2D) and linked to peripheral insulin resistance. However, the effect of acylCs on pancreatic β-cell function is not well understood. Here, we profiled circulating acylCs in two diabetes cohorts: 1 ) women with gestational diabetes mellitus (GDM) and 2 ) women with recent GDM who later developed impaired glucose tolerance (IGT), new-onset T2D, or returned to normoglycemia within a 2-year follow-up period. We observed a specific elevation in serum medium-chain (M)-acylCs, particularly hexanoyl- and octanoylcarnitine, among women with GDM and individuals with T2D without alteration in long-chain acylCs. Mice treated with M-acylCs exhibited glucose intolerance, attributed to impaired insulin secretion. Murine and human islets exposed to elevated levels of M-acylCs developed defects in glucose-stimulated insulin secretion and this was directly linked to reduced mitochondrial respiratory capacity and subsequent ability to couple glucose metabolism to insulin secretion. In conclusion, our study reveals that an elevation in circulating M-acylCs is associated with GDM and early stages of T2D onset and that this elevation directly impairs β-cell function. © 2018 by the American Diabetes Association.

  1. Comparison of electrochemical skin conductance and vibration perception threshold measurement in the detection of early diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Amit Goel

    Full Text Available The early diagnosis of diabetic peripheral neuropathy (DPN is challenging. Sudomotor dysfunction is one of the earliest detectable abnormalities in DPN. The present study aimed to determine the diagnostic performance of the electrochemical skin conductance (ESC test in detecting early DPN, compared with the vibration perception threshold (VPT test and diabetic neuropathy symptom (DNS score, using the modified neuropathy disability score (NDS as the reference standard. Five hundred and twenty-three patients with type 2 diabetes underwent an NDS-based clinical assessment for neuropathy. Participants were classified into the DPN and non-DPN groups based on the NDS (≥ 6. Both groups were evaluated further using the DNS, and VPT and ESC testing. A receiver-operator characteristic (ROC curve analysis was performed to compare the efficacy of ESC measurements with those of DNS and VPT testing in detecting DPN. The DPN group (n = 110, 21% had significantly higher HbA1c levels and longer diabetes durations compared with the non-DPN group (n = 413. The sensitivity of feet ESC 15 V, and DNS ≥ 1, were 16.4, 10.9 and 1.8, respectively. ESC measurement is an objective and sensitive technique for the early detection of DPN. Feet ESC measurement was superior to VPT testing for identifying patients with early DPN.

  2. Glycogen synthase kinase-3: a key kinase in retinal neuron apoptosis in early diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Li Zhaohui; Ma Ling; Chen Xiaodong; Li Yonghao; Li Shiyi; Zhang Jinglin; Lu Lin

    2014-01-01

    .Conclusion GSK-3 kinase is closely related to retinal neuron apoptosis,and the application of the GSK-3 inhibitor lithium chloride can reduce retinal neuron apoptosis in early diabetic retinopathy.

  3. Universal HbA1c Measurement in Early Pregnancy to Detect Type 2 Diabetes Reduces Ethnic Disparities in Antenatal Diabetes Screening: A Population-Based Observational Study.

    Directory of Open Access Journals (Sweden)

    R C E Hughes

    Full Text Available In response to the type 2 diabetes epidemic, measuring HbA1c with the first-antenatal blood screen was recently recommended in NZ. This would enable prompt treatment of women with unrecognised type 2 diabetes, who may otherwise go undetected until the gestational diabetes (GDM screen. We compare inter-ethnic antenatal screening practices to examine whether the HbA1c test would be accessed by ethnicities most at risk of diabetes, and we determined the prevalence of unrecognised type 2 diabetes and prediabetes in our pregnant population. This is an observational study of pregnancies in Christchurch NZ during 2008-2010. Utilising electronic databases, we matched maternal characteristics to first-antenatal bloods, HbA1c, and GDM screens (glucose challenge tests and oral glucose tolerance tests. Overall uptake of the first-antenatal bloods versus GDM screening was 83.1% and 53.8% respectively in 11,580 pregnancies. GDM screening was lowest in Māori 39.3%, incidence proportion ratio (IPR 0.77 (0.71, 0.84 compared with Europeans. By including HbA1c with the first-antenatal bloods, the number screened for diabetes increases by 28.5% in Europeans, 40.0% in Māori, 28.1% in Pacific People, and 26.7% in 'Others' (majority of Asian descent. The combined prevalence of unrecognised type 2 diabetes and prediabetes by NZ criteria, HbA1c ≥5.9% (41mmol/mol, was 2.1% in Europeans, Māori 4.7% IPR 2.59 (1.71, 3.93, Pacific People 9.5% IPR 4.76 (3.10, 7.30, and 'Others' 6.2% IPR 2.99 (2.19, 4.07. Applying these prevalence data to 2013 NZ national births data, routine antenatal HbA1c testing could have identified type 2 diabetes in 0.44% and prediabetes in 3.96% of women. Routine HbA1c measurement in early pregnancy is an ideal screening opportunity, particularly benefitting vulnerable groups, reducing ethnic disparities in antenatal diabetes screening. This approach is likely to have world-wide relevance and applicability. Further research is underway to

  4. Early Antenatal Prediction of Gestational Diabetes in Obese Women: Development of Prediction Tools for Targeted Intervention.

    Directory of Open Access Journals (Sweden)

    Sara L White

    Full Text Available All obese women are categorised as being of equally high risk of gestational diabetes (GDM whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0-18+6 weeks' gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337 developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria. A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios provided an area under the curve of 0.71 (95%CI 0.68-0.74. This increased to 0.77 (95%CI 0.73-0.80 with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c, fructosamine, adiponectin, sex hormone binding globulin, triglycerides, but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74-0.81. Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described

  5. [Ventricular tachyarrhythmias in patients with cardiomyopathy

    DEFF Research Database (Denmark)

    Henningsen, K.; Christensen, A.H.; Svendsen, Jesper Hastrup

    2008-01-01

    by disease, gender, age, previous cardiac arrest and treatment with implantable cardioverter-defibrillator (ICD). RESULTS: 993 patients were screened and 128 patients with cardiomyopathy were identified, corresponding to 13% of the screened patients. 58 (45%) of the patients had dilated cardiomyopathy (DCM......), 57 (45%) patients had arrhythmogenic right ventricular cardiomyopathy (ARVC) and 13 (10%) had hypertrophic cardiomyopathy (HCM). The average age was 44 years for HCM, 41 years for ARVC and 58 years for DCM. The majority of the patients were male. ICD treatment was used in 95% of the patients...... with ARVC, 70% of the patients with HCM and 59% of the patients with DCM. Only 5 patients had previous cardiac arrest without reversible cause. CONCLUSION: The study shows that cardiomyopathies are relatively frequent causes of ventricular tachyarrhythmias in patients discharged from a specialised...

  6. Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

    Directory of Open Access Journals (Sweden)

    Aline Cristina Tavares

    2012-01-01

    Full Text Available Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

  7. Myocardial involvement in diabetic patients evaluated by exercise thallium-201 scintigraphy and cardiac catheterization

    International Nuclear Information System (INIS)

    Mizuno, Sumio; Genda, Akira; Nakayama, Akira; Igarashi, Yutaka; Takeda, Ryoyu

    1985-01-01

    To evaluate myocardial involvement in diabetes mellitus, we studied 39 patients with negative double-Master's test and without hypertension by exercise thallium-201 (Tl-201) myocardial scintigraphy using a bicycle ergometer. Among the 39 patients, 12 (30.8 %) showed filling defects in the scintigrams (positive cases), including eight with stress-induced defects and four with fixed defects. The positive cases had higher scores of diabetic complications (3.6 +- 2.4 vs 2.1 +- 1.8; p < 0.05) and longer durations of diabetes as compared with those of the negative cases. The frequency of insulin therapy was also greater in the positive cases. Eleven patients (5 positive and 6 negative cases) who underwent cardiac catheterization had no significant stenotic lesions of their coronary arteries. However, all of the positive cases showed abnormal wall motion, mainly hypokinesis, by left ventriculography (LVG). The abnormalities of the LVG corresponded to the findings of the scintigrams (i.e. filling defects and decrease in washout ratios by circumferential profile analysis). These results suggest that in some diabetics myocardial involvement exists in the early stage without overt cardiac disease and exercise Tl-201 scintigraphy is useful in detecting pre-clinical cardiomyopathy. Cardiomyopathy in diabetics seems to be due to disturbances of the myocardial microcirculation. (author)

  8. Diabetes risk score in the United Arab Emirates: a screening tool for the early detection of type 2 diabetes mellitus

    Science.gov (United States)

    Sulaiman, Nabil; Hussein, Amal; Elbadawi, Salah; Abusnana, Salah; Zimmet, Paul

    2018-01-01

    Objective The objective of this study was to develop a simple non-invasive risk score, specific to the United Arab Emirates (UAE) citizens, to identify individuals at increased risk of having undiagnosed type 2 diabetes mellitus. Research design and methods A retrospective analysis of the UAE National Diabetes and Lifestyle data was conducted. The data included demographic and anthropometric measurements, and fasting blood glucose. Univariate analyses were used to identify the risk factors for diabetes. The risk score was developed for UAE citizens using a stepwise forward regression model. Results A total of 872 UAE citizens were studied. The overall prevalence of diabetes in the UAE adult citizens in the Northern Emirates was 25.1%. The significant risk factors identified for diabetes were age (≥35 years), a family history of diabetes mellitus, hypertension, body mass index ≥30.0 and waist-to-hip ratio ≥0.90 for males and ≥0.85 for females. The performance of the model was moderate in terms of sensitivity (75.4%, 95% CI 68.3 to 81.7) and specificity (70%, 95% CI 65.8 to 73.9). The area under the receiver-operator characteristic curve was 0.82 (95% CI 0.78 to 0.86). Conclusions A simple, non-invasive risk score model was developed to help to identify those at high risk of having diabetes among UAE citizens. This score could contribute to the efficient and less expensive earlier detection of diabetes in this high-risk population. PMID:29629178

  9. Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes

    OpenAIRE

    Bernstein, Judith A; McCloskey, Lois; Gebel, Christina M; Iverson, Ronald E; Lee-Parritz, Aviva

    2016-01-01

    Objectives Gestational diabetes mellitus (GDM) greatly increases the risk of developing diabetes in the decade after delivery, but few women receive appropriately timed postpartum glucose testing (PPGT) or a referral to primary care (PC) for continued monitoring. This qualitative study was designed to identify barriers and facilitators to testing and referral from patient and providers' perspectives. Methods We interviewed patients and clinicians in depth about knowledge, values, priorities, ...

  10. Diabetes

    Science.gov (United States)

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

  11. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

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

  12. Evaluation of serum zonulin for use as an early predictor for gestational diabetes.

    Science.gov (United States)

    Mokkala, K; Tertti, K; Rönnemaa, T; Vahlberg, T; Laitinen, K

    2017-03-20

    Diet has an important role in regulating intestinal permeability and subsequently the risk for metabolic disorders. In this observational study, we examined whether serum intestinal permeability marker zonulin, could be used as a predictor for gestational diabetes mellitus (GDM). Serum zonulin concentration was measured in early pregnancy in overweight or obese pregnant women (n=88) at risk for developing GDM. Serum zonulin was associated with higher odds of GDM (adjusted OR for 1 ng ml -1 increase in zonulin: 1.08, 95% CI: 1.02-1.15; P=0.009), diagnosed by a 2-h 75-g oral glucose tolerance test at late pregnancy. The optimal cutoff value was 43.3 ng ml -1 , with sensitivity of 88% (95% CI: 71-100%) and specificity of 47% (95% CI: 33-58%). The area under the ROC-curve was 0.67 (95% CI: 0.54-0.81). Our results show an association between increased early-pregnancy serum zonulin concentration and GDM, suggesting zonulin as a possible predictor for GDM.

  13. Peripartum cardiomyopathy: A contemporary review

    Directory of Open Access Journals (Sweden)

    Akshai Bhandary

    2018-01-01

    Full Text Available Peripartum cardiomyopathy (PPCM is a rare, potentially life-threatening disorder affecting women in late pregnancy and the postpartum period. Historically, PPCM was not recognized as a separate disease entity until the 1930s. Further research has since led to the identification of at-risk demographics, theories on etiology, and new targets of therapy. Management to date has largely been focused on guideline-based treatment for heart failure with reduced ejection fraction. However, newer studies have shown the efficacy of novel therapies. In this article, we will review the pathogenesis and diagnosis of PPCM and conclude with some of the newest therapies being offered.

  14. Ergotamine-Induced Takotsubo Cardiomyopathy.

    Science.gov (United States)

    Ozpelit, Ebru; Ozpelit, Mehmet E; Akdeniz, Bahri; Göldeli, Özhan

    2016-01-01

    Takotsubo cardiomyopathy (TC) is a recently increasing diagnosed disease showed by transient apical or mid-apical left ventricular dysfunction. It is known as a disease of postmenopausal women, which is usually triggered by emotional or physical stress. Although the trigger is mostly endogenous, some drugs have also been reported as the cause. Published case reports of TC associated with drug usage consist of sympathomimetic drugs, inotropic agents, thyroid hormone, cocaine, and 5-fluorouracil. We present an unusual case of TC in which the possible trigger is ergotamine toxicity.

  15. Takotsubo cardiomyopathy: a case report.

    Science.gov (United States)

    Johar, Sandeep; Prasad, Heramba; Kozman, Hani

    2007-01-01

    A 57-year-old Caucasian woman presented to the emergency department with chest discomfort after testifying in a child custody battle in court. Electrocardiography (ECG) revealed ST-segment elevation in the lateral leads, and T-wave inversions in the inferior and lateral leads. The creatine kinase, creatine kinase-MB, and troponin I concentrations were elevated on presentation. Despite the ECG changes and elevated cardiac markers, coronary angiography demonstrated normal arteries. Left ventricular angiogram revealed an aneurysm at the apex. Takotsubo cardiomyopathy was diagnosed on the basis of these characteristic findings. The patient was discharged on her third hospital day without any complications from the coronary angiography.

  16. Peripartum Cardiomyopathy: A Current Review

    Directory of Open Access Journals (Sweden)

    Katie M. Twomley

    2010-01-01

    Full Text Available Peripartum cardiomyopathy (PPCM is a rare but potentially lethal complication of pregnancy occurring in approximately 1 : 3,000 live births in the United States although some series report a much higher incidence. African-American women are particularly at risk. Diagnosis requires symptoms of heart failure in the last month of pregnancy or within five months of delivery in the absence of recognized cardiac disease prior to pregnancy as well as objective evidence of left ventricular systolic dysfunction. This paper provides an updated, comprehensive review of PPCM, including emerging insights into the etiology of this disorder as well as current treatment options.

  17. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

    Science.gov (United States)

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mothers with gestational diabetes are more likely to give birth to children who experience early weight problems.

    Science.gov (United States)

    Hakanen, T; Saha, M T; Salo, M K; Nummi, T; Harjunmaa, U; Lipiäinen, L; Vuorela, N

    2016-10-01

    We tracked the body mass index (BMI) of children born to mothers with or without gestational diabetes mellitus (GDM) or type 1 diabetes from birth to 12 years of age and examined the trends in both diseases. Antenatal and postnatal health survey data were collected from 6909 Finnish children born at six time points between 1974 and 2004. We compared the BMI trajectory between the offspring of mothers with and without GDM or type 1 diabetes, and the association between GDM and overweight offspring was analysed. The prevalence of GDM and type 1 diabetes increased markedly over the study period. The BMI trajectory in the GDM or type 1 diabetes offspring differed significantly from the nondiabetic offspring. The timing of adiposity rebound occurred significantly earlier in the GDM (4.8 years) and type 1 diabetes (4.4 years) groups than the nondiabetic group (5.5 years). GDM offspring were more likely to be overweight at five, seven and 12 years of age (24.6%, 28.1%, 29.4%) than nondiabetic offspring (15.6%, 18.3%, 18.1%). Children born to mothers with GDM were significantly more likely to be overweight at an early age than those born to nondiabetic mothers. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  19. Angiogenic dysfunction in bone marrow-derived early outgrowth cells from diabetic animals is attenuated by SIRT1 activation.

    Science.gov (United States)

    Yuen, Darren A; Zhang, Yanling; Thai, Kerri; Spring, Christopher; Chan, Lauren; Guo, Xiaoxin; Advani, Andrew; Sivak, Jeremy M; Gilbert, Richard E

    2012-12-01

    Impaired endothelial repair is a key contributor to microvascular rarefaction and consequent end-organ dysfunction in diabetes. Recent studies suggest an important role for bone marrow-derived early outgrowth cells (EOCs) in mediating endothelial repair, but the function of these cells is impaired in diabetes, as in advanced age. We sought to determine whether diabetes-associated EOC dysfunction might be attenuated by pharmacological activation of silent information regulator protein 1 (SIRT1), a lysine deacetylase implicated in nutrient-dependent life span extension in mammals. Despite being cultured in normal (5.5 mM) glucose for 7 days, EOCs from diabetic rats expressed less SIRT1 mRNA, induced less endothelial tube formation in vitro and neovascularization in vivo, and secreted less of the proangiogenic ELR(+) CXC chemokines CXCL1, CXCL3, and CXCL5. Ex vivo SIRT1 activation restored EOC chemokine secretion and increased the in vitro and in vivo angiogenic activity of EOC conditioned medium derived from diabetic animals to levels similar to that derived from control animals. These findings suggest a pivotal role for SIRT1 in diabetes-induced EOC dysfunction and that its pharmacologic activation may provide a new strategy for the restoration of EOC-mediated repair mechanisms.

  20. Healthy Lifestyle During Early Pregnancy and Risk of Gestational Diabetes Mellitus.

    Science.gov (United States)

    Badon, Sylvia E; Enquobahrie, Daniel A; Wartko, Paige D; Miller, Raymond S; Qiu, Chunfang; Gelaye, Bizu; Sorensen, Tanya K; Williams, Michelle A

    2017-08-01

    Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4). Regression models were used to determine relative risk of GDM (n = 140 cases) in relation to healthy lifestyle. Twenty percent of participants had a healthy diet, 66% were physically active, 95% were nonsmokers, and 55% had low stress. Each 1-point increase in lifestyle score was associated with a 21% lower risk of GDM (95% confidence interval: 0.65, 0.96) after adjustment for age, race, and nulliparity. Adjustment for prepregnancy body mass index, prepregnancy physical activity, and prepregnancy smoking attenuated the associations slightly. Associations were similar in normal-weight and overweight/obese women. In this study, a composite measure of healthy lifestyle during early pregnancy was associated with substantially lower GDM risk. Public health messaging and interventions promoting multiple aspects of a healthy lifestyle during early pregnancy should be considered for GDM prevention. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Eating disorders in persons with type 1 diabetes: A focus group investigation of early eating disorder risk.

    Science.gov (United States)

    Powers, Margaret A; Richter, Sara A; Ackard, Diann M; Cronemeyer, Catherine

    2016-12-01

    Through focus groups, we examined the development and maintenance of an eating disorder in 16 females with type 1 diabetes and an eating disorder. The quotes and qualitative data summaries provide rich insights into understanding why those with type 1 diabetes are at increased risk for eating disorders. Content analyses revealed five themes pertinent to the dual diagnosis (feeling different, difficulty with control/coping, body image, feelings, and quality of life) of which four themes were relevant to eating disorder development. Findings support early identification of those at risk and inform interventions to mitigate development of an eating disorder. © The Author(s) 2015.

  2. Early life opportunities for prevention of diabetes in low and middle income countries

    Directory of Open Access Journals (Sweden)

    Hanson Mark A

    2012-11-01

    Full Text Available Abstract Background The global burden of diabetes and other non-communicable diseases is rising dramatically worldwide and is causing a double poor health burden in low- and middle-income countries. Early life influences play an important part in this scenario because maternal lifestyle and conditions such as gestational diabetes and obesity affect the risk of diabetes in the next generation. This indicates important periods during the lifecourse when interventions could have powerful affects in reducing incidence of non-communicable diseases. However, interventions to promote diet and lifestyle in prospective parents before conception have not received sufficient attention, especially in low- and middle-income countries undergoing socio-economic transition. Discussion Interventions to produce weight loss in adults or to reduce weight gain in pregnancy have had limited success and might be too late to produce the largest effects on the health of the child and his/her later risk of non-communicable diseases. A very important factor in the prevention of the developmental component of diabetes risk is the physiological state in which the parents enter pregnancy. We argue that the most promising strategy to improve prospective parents’ body composition and lifestyle is the promotion of health literacy in adolescents. Multiple but integrated forms of community-based interventions that focus on nutrition, physical activity, family planning, breastfeeding and infant feeding practices are needed. They need to address the wider social economic context in which adolescents live and to be linked with existing public health programmes in sexual and reproductive health and maternal and child health initiatives. Summary Interventions aimed at ensuring a healthy body composition, diet and lifestyle before pregnancy offer a most effective solution in many settings, especially in low- and middle-income countries undergoing socio-economic transition. Preparing

  3. Low cardiorespiratory fitness in people at risk for type 2 diabetes: early marker for insulin resistance

    Directory of Open Access Journals (Sweden)

    Leite Silmara AO

    2009-09-01

    Full Text Available Abstract Purpose There is a significant association between insulin resistance and low cardiorespiratory fitness in nondiabetic subjects. In a population with risk factors for type 2 diabetes (T2DM, before they are insulin resistant, we investigated low exercise capacity (VO2max as an early marker of impaired insulin sensitivity in order to determine earlier interventions to prevent development of insulin resistance syndrome (IRS and T2DM. Methods Cross-sectional analyses of data on 369 (78 men and 291 women people at risk for IRS and T2DM, aged 45.6 +/- 10 years (20-65 years old from the Community Diabetes Prevention Project in Minnesota were carried out. The cardiorespiratory fitness (VO2max by respiratory gas exchange and bicycle ergometer were measured in our at risk non insulin resistant population and compared with a control group living in the same geographic area. Both groups were equally sedentary, matched for age, gender and BMI. Results The most prevalent abnormality in the study population was markedly low VO2max when compared with general work site screening control group, (n = 177; 137F; 40 M, mean age 40 ± 11 years; BMI = 27.8 ± 6.1 kg/m2. Individuals at risk for IRS and T2DM had a VO2max (22 ± 6 ml/kg/min 15% lower than the control group VO2max (26 ± 9 ml/kg/min (p 2max was inversely correlated with HOMA-IR (r = -0.30, p Conclusions Decreased VO2max is correlated with impaired insulin sensitivity and was the most prevalent abnormality in a population at risk for IRS and T2DM but without overt disease. This raises the possibility that decreased VO2 max is among the earliest indicators of IRS and T2DM therefore, an important risk factor for disease progression.

  4. Persistent organic pollutants in early pregnancy and risk of gestational diabetes mellitus.

    Science.gov (United States)

    Vafeiadi, Marina; Roumeliotaki, Theano; Chalkiadaki, Georgia; Rantakokko, Panu; Kiviranta, Hannu; Fthenou, Eleni; Kyrtopoulos, Soterios A; Kogevinas, Manolis; Chatzi, Leda

    2017-01-01

    Persistent organic pollutants (POPs) are a group of diverse substances, including polychlorinated biphenyls (PCBs) and organochlorine pesticides that are resistant to biodegradation and ubiquitously present in our environment. Exposure to endocrine disrupting chemicals such as POPs has been linked to type 2 diabetes and metabolic disturbances in epidemiological and animal studies, but little is known about POPs exposure during pregnancy and the development of gestational diabetes mellitus (GDM). The purpose of this study was to determine the extent to which exposure to current low levels of different POPs in the first trimester of pregnancy is associated with GDM risk in 939 women from the "Rhea" pregnancy cohort in Crete, Greece. Concentrations of several PCBs, dichlorodiphenyldichloroethene (DDE), and hexachlorobenzene (HCB) were determined in first trimester maternal serum by triple quadrupole mass spectrometry. We defined total PCBs as the sum of all congeners, nondioxin-like PCBs as the sum of PCB 153, 138, 170 and 180, and dioxin-like PCBs as the sum of PCB 118 and 156. Pregnant women were screened for gestational diabetes mellitus (GDM) between 24 and 28weeks of gestation, and GDM was defined by the criteria proposed by Carpenter and Coustan. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models. Of the 939 women, 68 (7%) developed GDM. Serum concentrations of POPs were higher in women with GDM. Women in the medium and high tertiles of PCBs had 3.90 (95% CI: 1.37, 11.06) and 3.60 (95% CI: 1.14, 11.39) fold respectively higher odds of developing GDM compared to women in the lowest tertile of PCB exposure after adjusting for pre-pregnancy BMI and several other confounders. Odds of GDM for women in the medium and high tertiles of dioxin-like PCBs was 5.63 (95% CI: 1.81, 17.51) and 4.71 (95% CI: 1.38, 16.01) and for nondioxin-like PCBs 2.36 (95% CI: 0.89, 6.23) and 2.26 (95% CI: 0.77, 6

  5. Diabetic Retinopathy

    Science.gov (United States)

    ... pregnancy may have rapid onset or worsening of diabetic retinopathy. Symptoms and Detection What are the symptoms of diabetic retinopathy and ... with diabetes protect their vision? Vision lost to diabetic retinopathy is ... However, early detection and treatment can reduce the risk of blindness ...

  6. Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Robledo, Candace A. [Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Division of Intramural Population Health Research, Epidemiology Branch, Rockville, MD 20892 (United States); Mendola, Pauline, E-mail: pauline.mendola@mail.nih.gov [Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Division of Intramural Population Health Research, Epidemiology Branch, Rockville, MD 20892 (United States); Yeung, Edwina; Männistö, Tuija [Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Division of Intramural Population Health Research, Epidemiology Branch, Rockville, MD 20892 (United States); Sundaram, Rajeshwari; Liu, Danping [Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Division of Intramural Population Health Research, Biostatistics and Bioinformatics Branch, Rockville, MD 20892 (United States); Ying, Qi [Texas A& M University, Zachary Department of Civil Engineering, College Station, TX 77845 (United States); Sherman, Seth [The EMMES Corporation, Rockville, MD 20852 (United States); Grantz, Katherine L. [Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Division of Intramural Population Health Research, Epidemiology Branch, Rockville, MD 20892 (United States)

    2015-02-15

    Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5 μm (PM{sub 2.5}) and PM{sub 2.5} constituents, PM ≤ 10 μm (PM{sub 10}), nitrogen oxides (NO{sub x}), carbon monoxide, sulfur dioxide (SO{sub 2}) and ozone (O{sub 3}) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1–24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. Results: Preconception maternal exposure to NO{sub X} (RR=1.09, 95% CI: 1.04, 1.13) and SO{sub 2} (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O{sub 3} was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. Conclusion: Maternal exposures to NO{sub x} and SO{sub 2} preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O{sub 3} appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation. - Highlights: • Air pollution may be related to gestational diabetes (GDM). • No prior studies have examined preconception exposure. • Maternal exposure to NO{sub x} and SO{sub 2} before conception increased subsequent GDM risk. • NO{sub x} and SO{sub 2} exposure in the first seven weeks of pregnancy also increased

  7. Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus

    International Nuclear Information System (INIS)

    Robledo, Candace A.; Mendola, Pauline; Yeung, Edwina; Männistö, Tuija; Sundaram, Rajeshwari; Liu, Danping; Ying, Qi; Sherman, Seth; Grantz, Katherine L.

    2015-01-01

    Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5 μm (PM 2.5 ) and PM 2.5 constituents, PM ≤ 10 μm (PM 10 ), nitrogen oxides (NO x ), carbon monoxide, sulfur dioxide (SO 2 ) and ozone (O 3 ) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1–24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. Results: Preconception maternal exposure to NO X (RR=1.09, 95% CI: 1.04, 1.13) and SO 2 (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O 3 was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. Conclusion: Maternal exposures to NO x and SO 2 preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O 3 appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation. - Highlights: • Air pollution may be related to gestational diabetes (GDM). • No prior studies have examined preconception exposure. • Maternal exposure to NO x and SO 2 before conception increased subsequent GDM risk. • NO x and SO 2 exposure in the first seven weeks of pregnancy also increased GDM risk. • Early exposure to O 3 reduced GDM risk but risk increased

  8. A Machine Learning Ensemble Classifier for Early Prediction of Diabetic Retinopathy.

    Science.gov (United States)

    S K, Somasundaram; P, Alli

    2017-11-09

    The main complication of diabetes is Diabetic retinopathy (DR), retinal vascular disease and it leads to the blindness. Regular screening for early DR disease detection is considered as an intensive labor and resource oriented task. Therefore, automatic detection of DR diseases is performed only by using the computational technique is the great solution. An automatic method is more reliable to determine the presence of an abnormality in Fundus images (FI) but, the classification process is poorly performed. Recently, few research works have been designed for analyzing texture discrimination capacity in FI to distinguish the healthy images. However, the feature extraction (FE) process was not performed well, due to the high dimensionality. Therefore, to identify retinal features for DR disease diagnosis and early detection using Machine Learning and Ensemble Classification method, called, Machine Learning Bagging Ensemble Classifier (ML-BEC) is designed. The ML-BEC method comprises of two stages. The first stage in ML-BEC method comprises extraction of the candidate objects from Retinal Images (RI). The candidate objects or the features for DR disease diagnosis include blood vessels, optic nerve, neural tissue, neuroretinal rim, optic disc size, thickness and variance. These features are initially extracted by applying Machine Learning technique called, t-distributed Stochastic Neighbor Embedding (t-SNE). Besides, t-SNE generates a probability distribution across high-dimensional images where the images are separated into similar and dissimilar pairs. Then, t-SNE describes a similar probability distribution across the points in the low-dimensional map. This lessens the Kullback-Leibler divergence among two distributions regarding the locations of the points on the map. The second stage comprises of application of ensemble classifiers to the extracted features for providing accurate analysis of digital FI using machine learning. In this stage, an automatic detection

  9. Cardiac magnetic resonance assessment of takotsubo cardiomyopathy

    International Nuclear Information System (INIS)

    Abbas, A.; Sonnex, E.; Pereira, R.S.; Coulden, R.A.

    2016-01-01

    Takotsubo cardiomyopathy is an important condition that can be difficult to differentiate from acute coronary syndrome on the basis of clinical, electrocardiogram, and cardiac enzyme assessment alone. Although coronary angiography remains important in the acute assessment of patients with suspected takotsubo cardiomyopathy, cardiac magnetic resonance (CMR) has emerged over the last decade as an important non-invasive imaging tool in the diagnosis and follow-up of this condition. We present a review highlighting the CMR features of takotsubo cardiomyopathy and its complications with particular focus on differentiating this condition from acute myocardial infarction and myocarditis.

  10. Acute pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman undergoing transvaginal cervical cerclage: A case report.

    Science.gov (United States)

    Lee, Jae-Young; Kwon, Hyun-Jung; Park, Sang-Wook; Lee, Yu-Mi

    2017-01-01

    The physiological changes associated with pregnancy may predispose pregnant women to pulmonary edema. Other known causes of pulmonary edema during pregnancy include tocolytic drugs, preeclampsia, eclampsia, and peripartum cardiomyopathy. We describe a rare case of pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman at 14 weeks of gestation who was undergoing emergency transvaginal cervical cerclage. Intraoperative chest radiography revealed severe pulmonary edema and echocardiography indicated moderate left ventricular dysfunction with akinesia of the mid to apical left ventricular wall segment, which is reflective of takotsubo cardiomyopathy. With early detection and appropriate management, the patient was stabilized in a relatively short period of time. Based on her clinical signs and symptoms, we suspect that the pulmonary edema was caused by takotsubo cardiomyopathy.

  11. Diabetes

    Science.gov (United States)

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

  12. Diabetes

    Data.gov (United States)

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

  13. Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Lakdawala, Neal K; Thune, Jens Jakob; Maron, Barry J

    2011-01-01

    In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) wall thickness is still normal. However, the ECG features of mutation carriers have not been fully...

  14. Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse

    DEFF Research Database (Denmark)

    Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

    2012-01-01

    , a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes. Methods: Accordingly, one group of mice received vancomycin from birth until weaning (day 28), while another group...... lower for the neonatally treated group compared with the untreated group, whereas the insulitis score and blood glucose levels were significantly lower for the mice treated as adults compared with the other groups. Mucosal inflammation was investigated by intracellular cytokine staining of the small...... genera of Gram-positive and Gram-negative microbes while, interestingly, one single species, Akkermansia muciniphila, became dominant. Conclusions/interpretation: The early postnatal period is a critical time for microbial protection from type 1 diabetes and it is suggested that the mucolytic bacterium A...

  15. Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

    NARCIS (Netherlands)

    Lirk, P.; Verhamme, C.; Boeckh, R.; Stevens, M. F.; ten Hoope, W.; Gerner, P.; Blumenthal, S.; de Girolami, U.; van Schaik, I. N.; Hollmann, M. W.; Picardi, S.

    2015-01-01

    The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control

  16. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Mervi E. Hyvönen

    2015-01-01

    Full Text Available The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.

  17. Frequency of echocardiographic complications of dilated cardiomyopathy at a tertiary care hospital

    International Nuclear Information System (INIS)

    Rashid, A.; Ahmed, H.N.; Ahmed, N.

    2012-01-01

    Dilated cardiomyopathy can lead to a variety of complications recognisable on clinical, echocardiographic, electrocardiographic and radiographic assessment. Among this, transthoracic echocardiography has the dual advantage of being helpful in making the diagnosis of dilated cardiomyopathy as well as an effective tool in early recognition of certain complications for timely management to improve the quality of life of these patients. Methods: This descriptive (case series) study was undertaken at departments of medicine, cardiology, paediatrics and obs/gyn, Ayub Teaching Hospital, Abbottabad from July to December, 2008. fifty patients of dilated cardiomyopathy without age and gender discrimination were selected by convenience sampling. Those with hypertrophic and restrictive cardiomyopathies, valvular and congenital heart disease, hypertension and ischemic heart disease were excluded. Results: mean age was 47.12 +- 17.9 year with male predominance (males=34, females=16). Mean ejection fraction was 30.6 +- 6.9%. complications revealed on echocardiography were intracardiac thrombi (5, 10%), spontaneous echo contrast (5, 10%), pericardial effusion (6, 12%), mitral regurgitation (46, 92%), tricuspid (25, 50%), aortic (5, 10%), pulmonary (2, 4%) multi-valvular regurgitation (28, 56%), and left atrial dilatation (36, 72%). Conclusion: lv systolic dysfunction, cardiac thrombi, spontaneous echo contrast, mitral and tricuspid regurgitation and left atrial enlargement are important complications of dilated cardiomyopathy. echocardiography is important tool towards identification of these complications. (author)

  18. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    Science.gov (United States)

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  19. Successful treatment of inverted Takotsubo cardiomyopathy after severe traumatic brain injury with milrinone after dobutamine failure.

    Science.gov (United States)

    Mrozek, Ségolène; Srairi, Mohamed; Marhar, Fouad; Delmas, Clément; Gaussiat, François; Abaziou, Timothée; Larcher, Claire; Atthar, Vincent; Menut, Rémi; Fourcade, Olivier; Geeraerts, Thomas

    2016-01-01

    Takotsubo cardiomyopathy can occur at the early phase of severe acute brain injuries. In the case of cardiac output decrease or shock, the optimal treatment is still a matter of debate. Due to massive stress hormone release, the infusion of catecholamines may have limited effects and may even aggravate cardiac failure. Other inotropic agents may be an option. Levosimendan has been shown to have potential beneficial effects in this setting, although milrinone has not been studied. We report a case of a young female presenting with inverted Takotsubo cardiomyopathy syndrome after severe traumatic brain injury. Due to hemodynamic instability and increasing levels of infused norepinephrine, dobutamine infusion was begun but rapidly stopped due to tachyarrhythmia. Milrinone infusion stabilized the patient's hemodynamic status and improved cardiac output without deleterious effects. Milrinone could be a good alternative when inotropes are required in Takotsubo cardiomyopathy and when dobutamine infusion is associated with tachyarrhythmia. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The Use of a Novel Heart Failure Agent in the Treatment of Pregnancy-Associated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Vamsi C. Gaddipati

    2017-01-01

    Full Text Available Peripartum cardiomyopathy is an uncommon, pregnancy-related form of dilated cardiomyopathy that is associated with development of new-onset left ventricular dysfunction. Its etiology is presently unknown, but current standard of care involves the use of typical drug therapy for the treatment of heart failure. Pregnancy-associated cardiomyopathy (PACM is a similar condition that refers to patients who develop such symptoms prior to the last month of pregnancy. We report the case of a nulliparous Caucasian female who develops early, severe PACM during her first pregnancy with postpartum persistence of New York Heart Association class II-III symptoms despite medical therapy. The use of the novel heart failure agent, sacubitril/valsartan (Entresto, is initiated with near-complete resolution of her symptoms.

  1. Early Detection of Diabetic Retinopathy in Fluorescent Angiography Retinal Images Using Image Processing Methods

    Directory of Open Access Journals (Sweden)

    Meysam Tavakoli

    2010-12-01

    Full Text Available Introduction: Diabetic retinopathy (DR is the single largest cause of sight loss and blindness in the working age population of Western countries; it is the most common cause of blindness in adults between 20 and 60 years of age. Early diagnosis of DR is critical for preventing vision loss so early detection of microaneurysms (MAs as the first signs of DR is important. This paper addresses the automatic detection of MAs in fluorescein angiography fundus images, which plays a key role in computer assisted diagnosis of DR, a serious and frequent eye disease. Material and Methods: The algorithm can be divided into three main steps. The first step or pre-processing was for background normalization and contrast enhancement of the image. The second step aimed at detecting landmarks, i.e., all patterns possibly corresponding to vessels and the optic nerve head, which was achieved using a local radon transform. Then, MAs were extracted, which were used in the final step to automatically classify candidates into real MA and other objects. A database of 120 fluorescein angiography fundus images was used to train and test the algorithm. The algorithm was compared to manually obtained gradings of those images. Results: Sensitivity of diagnosis for DR was 94%, with specificity of 75%, and sensitivity of precise microaneurysm localization was 92%, at an average number of 8 false positives per image. Discussion and Conclusion: Sensitivity and specificity of this algorithm make it one of the best methods in this field. Using local radon transform in this algorithm eliminates the noise sensitivity for microaneurysm detection in retinal image analysis.

  2. Insulin gene mutations resulting in early-onset diabetes: marked differences in clinical presentation, metabolic status, and pathogenic effect through endoplasmic reticulum retention

    DEFF Research Database (Denmark)

    Meur, Gargi; Simon, Albane; Harun, Nasret

    2009-01-01

    OBJECTIVE: Heterozygous mutations in the human preproinsulin (INS) gene are a cause of nonsyndromic neonatal or early-infancy diabetes. Here, we sought to identify INS mutations associated with maturity-onset diabetes of the young (MODY) or nonautoimmune diabetes in mid-adult life, and to explore...... the molecular mechanisms involved. RESEARCH DESIGN AND METHODS: The INS gene was sequenced in 16 French probands with unexplained MODY, 95 patients with nonautoimmune early-onset diabetes (diagnosed at ... with early-onset diabetes whose clinical presentation is compatible with MODY. These led to the production of (pre)proinsulin molecules with markedly different trafficking properties and effects on ER stress, demonstrating a range of molecular defects in the beta-cell....

  3. Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

    Science.gov (United States)

    Kondo, M; Nagao, Y; Mahbub, M H; Tanabe, Tsuyoshi; Tanizawa, Y

    2018-04-29

    To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m 2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin intolerance. Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. The early life origin theory in the development of cardiovascular disease and type 2 diabetes.

    Science.gov (United States)

    Lindblom, Runa; Ververis, Katherine; Tortorella, Stephanie M; Karagiannis, Tom C

    2015-04-01

    Life expectancy has been examined from a variety of perspectives in recent history. Epidemiology is one perspective which examines causes of morbidity and mortality at the population level. Over the past few 100 years there have been dramatic shifts in the major causes of death and expected life length. This change has suffered from inconsistency across time and space with vast inequalities observed between population groups. In current focus is the challenge of rising non-communicable diseases (NCD), such as cardiovascular disease and type 2 diabetes mellitus. In the search to discover methods to combat the rising incidence of these diseases, a number of new theories on the development of morbidity have arisen. A pertinent example is the hypothesis published by David Barker in 1995 which postulates the prenatal and early developmental origin of adult onset disease, and highlights the importance of the maternal environment. This theory has been subject to criticism however it has gradually gained acceptance. In addition, the relatively new field of epigenetics is contributing evidence in support of the theory. This review aims to explore the implication and limitations of the developmental origin hypothesis, via an historical perspective, in order to enhance understanding of the increasing incidence of NCDs, and facilitate an improvement in planning public health policy.

  5. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  6. Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide, prospective, population-based case-control study

    OpenAIRE

    Lindell, Nina; Carlsson, Annelie; Josefsson, Ann; Samuelsson, Ulf

    2018-01-01

    Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes. Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a t...

  7. Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis.

    Science.gov (United States)

    Batalla, A; Vicente, A; Bartrons, J; Prada, F; Fortuny, C; González-Enseñat, M A

    In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, leading to a poorer prognosis. Our objective was to determine the prevalence of DC in patients with EB seen in Hospital San Joan de Déu in Barcelona, Spain, between May 1986 and April 2015. This was a descriptive, cross-sectional chart-review study in which we recorded the type and main subtypes of EB and the presence or absence of DC. Fifty-seven patients with EB were found, 19 with EB simplex, 10 with junctional EB, 27 with dystrophic EB (14 dominant dystrophic and 13 recessive dystrophic), and just 1 with Kindler syndrome. DC was detected in only 2 patients with recessive dystrophic EB. Twenty-three patients had presented factors that could have had a causal relationship with the potential onset of DC. DC is a possible complication of EB, particularly in recessive dystrophic EB. Periodic follow-up should be performed to make an early diagnosis and start treatment. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Syncope in children with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    I. V. Leontyeva

    2014-01-01

    Full Text Available Seventy children aged 7 to 17 years with hypertrophic cardiomyopathy (HCM were examined; among them there were 11 syncope patients and 5 presyncope patients. The screening program included standard electrocardiography (ECG, Doppler echocardiogra-phy, 24-hour Holter ECG monitoring, and an incremental exercise testing (Bruce treadmill test. The markers of myocardial electrical instability were determined. In the children with HCM, syncope was established to be heterogeneous; it had an arrhythmogenic origin and, in most cases, occurred in the presence of tachyarrhythmia (44% or bradyarrythmia (25%; its vasovagal genesis was probable in one third of the examinees. The children with syncope were typified by the asymmetric, obstructive form of HCM, at the same tone there was most commonly left ventricular hypertrophy concurrent with left atrial enlargement. 24-hour Holter monitoring showed that bradycardia was prevalent in the patients, 3 patients were found to have more than 2-second cardiac rhythm pauses caused by second-degree atrioventricular block in 1 case or by sick sinus syndrome in 2. Nonsustained ventricular tachycardia was noted in two patients. The children with syncope were typified by the signs of myocardial electrical instability as a reduction in the early phase of heart rate turbulence and by impaired QT/RR interval adaptation as hyperadaptation. The paper presents the developed management tactics for children with syncope and indications for the implantation of a cardioverter defibrillator, a pacemaker, or an ECG loop recorder.

  9. Quality of life, anxiety and depression symptoms in early and late pregnancy in women with pregestational diabetes

    DEFF Research Database (Denmark)

    Do, Nicoline C; Secher, Anna L; Cramon, Per

    2017-01-01

    INTRODUCTION: The aim of this study was to explore changes in health-related quality of life, anxiety and depression symptoms during pregnancy in women with pregestational diabetes. MATERIAL AND METHODS: An observational cohort study including 137 pregnant women with pregestational diabetes (110...... with type 1 and 27 with type 2). To evaluate changes from early to late pregnancy, the internationally validated questionnaires 36-Item Short-Form Health Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS) were completed at 8 and 33 gestational weeks. RESULTS: From early to late pregnancy....... The HADS anxiety score improved slightly from 5.0 (3.3) to 4.5 (3.4) (p = 0.04) whereas the HADS depression score remained unchanged. The prevalence of women with HADS anxiety or depression score ≥8 did not change. CONCLUSIONS: Physical quality of life deteriorated whereas mental quality of life improved...

  10. Medulla Oblongata Hemorrhage and Reverse Takotsubo Cardiomyopathy.

    Science.gov (United States)

    Gobeske, Kevin T; Sarano, Maurice E; Fugate, Jennifer E; Wijdicks, Eelco F

    2017-12-19

    Acute brain injury with strong surges of adrenergic outflow has resulted in takotsubo cardiomyopathy, but there are surprisingly few reports of takotsubo cardiomyopathy after intracranial hemorrhage, and none have been described from hemorrhage within the brainstem. We describe a patient with reverse and reversible cardiomyopathy following a hemorrhage in the lateral medulla oblongata. While it is limited in size, the location of the hemorrhage caused acute systolic failure with left ventricular ejection fraction of 27% and vasopressor requirement for cardiogenic shock and pulmonary edema. There was full recovery after 7 days. Detailed case report. Hemorrhage into medulla oblongata pressor centers may result in acute, reversible, stress-induced cardiomyopathy, affirming the adrenergic origin of this condition.

  11. Genetics Home Reference: familial dilated cardiomyopathy

    Science.gov (United States)

    ... Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013 Sep;10(9):531- ... Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical ...

  12. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    Science.gov (United States)

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

    2016-04-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.

  13. Correlation of Michigan neuropathy screening instrument, United Kingdom screening test and electrodiagnosis for early detection of diabetic peripheral neuropathy.

    Science.gov (United States)

    Fateh, Hamid R; Madani, Seyed Pezhman; Heshmat, Ramin; Larijani, Bagher

    2015-01-01

    Almost half of Diabetic Peripheral Neuropathies (DPNs) are symptom-free. Methods including questionnaires and electrodiagnosis (EDx) can be fruitful for easy reach to early diagnosis, correct treatments of diabetic neuropathy, and so decline of complications for instance diabetic foot ulcer and prevention of high costs. The goal of our study was to compare effectiveness of the Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST) and electrophysiological evaluation in confirming diabetic peripheral neuropathy. One hundred twenty five known diabetes mellitus male and female subjects older than 18 with or without symptoms of neuropathy comprised in this research. All of them were interviewed in terms of demographic data, lipid profile, HbA1C, duration of disease, and history of retinopathy, so examined by Michigan neuropathy screening instrument (MNSI), United Kingdom screening test (UKST), and nerve conduction studies (NCS). The collected data were analyzed by SPSS software 18. One hundred twenty five diabetic patients (70 female, 55 male) were recruited in this study with a mean age of 58.7 ± 10.2, and mean duration of diabetes was 10.17 ± 6.9 years. The mean neuropathy score of MNSI and UKST were 2.3 (1.7) and 4.16 (2.9), respectively. Each instrument detected the peripheral neuropathy in 78 (69 %) and 91 (73 %) of patients, respectively. There was a significant relationship between number of neuropathies and mean of diabetes duration and development of retinopathy in both questionnaire evaluations and NCS. By nerve conduction study, neuropathy was detected in 121 (97 %) diabetic patients were reported in order 15 (12 %) mononeuropathy (as 33 % sensory and 67 % motor neuropathy) and 106 (85 %) polyneuropathy (as 31 % motor and 69 % sensorimotor neuropathy). As regards NCS is an objective, simple, and non-invasive tool and also can determine level of damage and regeneration in peripheral nerves, this study

  14. Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

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    Casper G. Schalkwijk

    2013-07-01

    Full Text Available Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyllysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

  15. The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

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    Wen Qin

    Full Text Available Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA; however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM. In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset 'classic' T1DM (n = 156, LADA (n = 174, T2DM (n = 195 and healthy cohorts (n = 166. Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ together with liquid chromatography tandem mass spectrometry (LC-MS to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0% proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1, which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM.

  16. Stress cardiomyopathy syndrome: a contemporary review.

    Science.gov (United States)

    Kapoor, Divya; Bybee, Kevin A

    2009-12-01

    Stress cardiomyopathy (SC) syndrome represents a reversible form of cardiomyopathy that commonly presents proximate to an acute emotional or physiologic stressor. The clinical presentation is similar to an acute coronary syndrome in the absence of obstructive coronary artery disease to explain the unusual distribution of associated transient wall motion abnormalities. Postmenopausal women seem particularly prone to SC for unclear reasons. The pathophysiology of the syndrome is unknown but may involve pathologic sympathetic myocardial stimulation.

  17. RATIONAL PHARMACOTHERAPY IN TAKOTSUBO CARDIOMYOPATHY

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    S. Marchev

    2012-01-01

    Full Text Available Rational pharmacotherapy in Takotsubo cardiomyopathy is based on clinical picture and data of functional and laboratory investigations of concrete patient. In patients with hypotension and moderate-to-severe left ventricle outflow tract obstruction inotropic agents must not to be used because they can worsen the degree of obstruction. In these patients beta blockers can improve hemodynamics by causing resolution of the obstruction. If intraventricular thrombus is detected, anticoagulation for at least 3 months is recommended. The duration of anticoagulant therapy may be modified depending on the extent of cardiac function recovery and thrombus resolution. For patients without thrombus but with severe left ventricular dysfunction, anticoagulation is recommended until the akinesis or dyskinesis has resolved but not more than 3 months.

  18. Takotsubo cardiomyopathy: an overlooked cause of chest pain

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    Leonardo Hackbart Bermudes

    2014-06-01

    Full Text Available Takotsubo cardiomyopathy (TTC, also known as apical ballooning syndrome, broken heart syndrome, or stress-induced cardiomyopathy, is defined as a transient disturbance of the left ventricle, which is quite often associated with electrocardiographic abnormalities that may mimic acute myocardial infarction. The syndrome is also characterized by a mild alteration of cardiac biomarkers in absence of coronary blood flow obstruction on the coronariography. Clinical presentation is often manifested by angina, dyspnea, syncope, and arrhythmias. Peculiarly, the left ventricle takes the form of “tako-tsubo” (a Japanese word for “octopus trap” on the imaging workup. The authors report the case of a post-menopausal, hypertensive, dyslipidemic and type-II diabetic woman admitted at the emergency service with acute chest pain post physical exertion. Electrocardiogram showed signs of ischemia and myocardial necrosis markers were mildly increased. Echocardiography and ventriculography showed apical and mid-ventricular akinesia, with mild atherosclerotic coronary lesions. Thus diagnostic workup and the outcome followed the diagnostic criteria for TTC. The authors called attention to the potential of overlooking this diagnosis, since this syndrome is still not widely recognized.

  19. A case of mitochondrial cardiomyopathy with restrictive transmitral filling pattern

    Directory of Open Access Journals (Sweden)

    Otsui K

    2012-04-01

    Full Text Available Kazunori Otsui, Nobutaka Inoue, Anna Tamagawa, Kazuo OnishiDepartment of Cardiovascular Medicine, Kobe Rosai Hospital, Kobe, JapanAbstract: A 61-year-old diabetic woman with a mitochondrial A3243G mutation was hospitalized for evaluation of breathlessness, general fatigue, and leg edema. Chest radiography revealed cardiomegaly with massive pleural effusion. Serum lactate, pyruvate, and brain natriuretic peptide concentrations were elevated. Transthoracic echocardiography revealed a restrictive pattern of transmitral flow, although systolic function of the left ventricle was only mildly impaired. Based on these findings and her clinical course, the patient was diagnosed with right-sided heart failure caused by mitochondrial cardiomyopathy associated with a restrictive transmitral filling pattern. Treatment with furosemide, enalapril, and eplerenone was effective, and improvement in her symptoms was associated with amelioration of transthoracic echocardiographic findings and a reduction in serum brain natriuretic peptide levels. Previous reports have indicated heterogeneity in the clinical features of mitochondrial cardiomyopathy in patients carrying the A3243G mutation; the present case highlights the substantial variability in the clinical features of this disease.Keywords: mitochondrial disease, A3243G mutation, diastolic dysfunction, transmitral flow

  20. Sulfur Hexafluoride 20% versus Lactated Ringer′s solution for Prevention of Early Postoperative Vitreous Hemorrhage after Diabetic Vitrectomy

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    Fereydoun Farrahi

    2010-01-01

    Full Text Available Purpose: To compare the hemostatic effect of sulfur hexafluoride 20% (SF6 20% with lactated Ringer′s solution for prevention of early postoperative vitreous hemorrhage following diabetic vitrectomy. Methods: In a prospective randomized clinical trial, 50 eyes undergoing diabetic vitrectomy were divided into two groups. At the conclusion of surgery, in one group the vitreous cavity was filled with SF6 20% while in the other group lactated Ringer′s solution was retained in the vitreous cavity. The two groups were compared for the rate of early postoperative vitreous hemorrhage. Results: The incidence of vitreous hemorrhage was lower in the SF6 group than the Ringer′s group 4 days (20% vs 68%, P=0.001, 7 days (24% vs 60%, P=0.01 and 4 weeks (16% vs 40%, P=0.059 after vitrectomy. Conclusion: In comparison with lactated Ringer′s solution, SF6 20% had a significant hemostatic effect especially in the early postoperative period after diabetic vitrectomy and reduced the incidence of vitreous hemorrhage.

  1. A Comparison of Screening Tools for the Early Detection of Peripheral Neuropathy in Adults with and without Type 2 Diabetes

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    Jennifer J. Brown

    2017-01-01

    Full Text Available Objective. Examine the effectiveness of the 128 Hz tuning fork, two monofilaments, and Norfolk Quality of Life Diabetic Neuropathy (QOL-DN questionnaire as tools for the early detection of diabetic peripheral neuropathy (DPN in overweight, obese, and inactive (OOI adults or those who have prediabetes (PD or type 2 diabetes (T2D. Research Design and Methods. Thirty-four adults (mean age 58.4 years ± 12.1 were divided by glycemia (10 OOI normoglycemic, 13 PD, and 11 T2D. Sural nerves were tested bilaterally with the NC-stat DPNCheck to determine sural nerve amplitude potential (SNAP and sural nerve conduction velocity (SNCV. All other testing results were compared to SNAP and SNCV. Results. Total 1 g monofilament scores significantly correlated with SNAP values and yielded the highest sensitivity and specificity combinations of tested measures. Total QOL-DN scores negatively correlated with SNAP values, as did QOL-DN symptoms. QOL-DN activities of daily living correlated with the right SNAP, and the QOL-DN small fiber subscore correlated with SNCV. Conclusions. The 1 g monofilament and total QOL-DN are effective, low-cost tools for the early detection of DPN in OOI, PD, and T2D adults. The 128 Hz tuning fork and 10 g monofilament may assist DPN screening as a tandem, but not primary, early DPN detection screening tools.

  2. Therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy

    Science.gov (United States)

    Liu, Hui-Hui; Xiong, Guo-Xin; Zhang, Li-Ping

    2017-06-01

    To investigate the therapeutic effect of the compound Danshen dripping pill combined with laser acupoint irradiation on early diabetic retinopathy, 19 patients with early diabetic retinopathy were randomly divided into a treatment group and a control group. The TaiYang, YangBai, YuYao and ZanZhu acupoints of patients in the treatment group were irradiated with a semiconductor laser combined with the oral compound Danshen dropping pills, while those in the control group only used the oral compound Danshen dropping pills. The indicators of vision, mean defect of light sensitivity in the visual field, renal function and fasting blood glucose, were examined to evaluate the efficacy. After treatment, the above indicators of patients in the two groups were significantly improved and there was a significant difference between the two groups. This showed that the compound Danshen dripping pills combined with the laser acupoint irradiation can improve the ischemic and anoxic state of early diabetic retinopathy and improve the visual field.

  3. Impact of high dose versus low dose atorvastatin on contrast induced nephropathy in diabetic patients with acute coronary syndrome undergoing early percutaneous coronary intervention

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    Haitham Galal

    2015-12-01

    Conclusion: No significant difference between high and low doses of atorvastatin in preventing CIN in diabetic patients with normal or mild renal impairment presenting with acute coronary syndrome who underwent early PCI.

  4. The Cost-Effectiveness of Three Screening Alternatives for People with Diabetes with No or Early Diabetic Retinopathy

    Science.gov (United States)

    Rein, David B; Wittenborn, John S; Zhang, Xinzhi; Allaire, Benjamin A; Song, Michael S; Klein, Ronald; Saaddine, Jinan B

    2011-01-01

    Objective To determine whether biennial eye evaluation or telemedicine screening are cost-effective alternatives to current recommendations for the estimated 10 million people aged 30–84 with diabetes but no or minimal diabetic retinopathy. Data Sources United Kingdom Prospective Diabetes Study, National Health and Nutrition Examination Survey, American Academy of Ophthalmology Preferred Practice Patterns, Medicare Payment Schedule. Study Design Cost-effectiveness Monte Carlo simulation. Data Collection/Extraction Methods Literature review, analysis of existing surveys. Principal Findings Biennial eye evaluation was the most cost-effective treatment option when the ability to detect other eye conditions was included in the model. Telemedicine was most cost-effective when other eye conditions were not considered or when telemedicine was assumed to detect refractive error. The current annual eye evaluation recommendation was costly compared with either treatment alternative. Self-referral was most cost-effective up to a willingness to pay (WTP) of U.S.$37,600, with either biennial or annual evaluation most cost-effective at higher WTP levels. Conclusions Annual eye evaluations are costly and add little benefit compared with either plausible alternative. More research on the ability of telemedicine to detect other eye conditions is needed to determine whether it is more cost-effective than biennial eye evaluation. PMID:21492158

  5. Cardiomyopathy

    Science.gov (United States)

    ... blood flow to the damaged or weakened heart muscle Heart transplant that may be tried when all other treatments have failed Recently, implantable artificial heart pumps have been developed. These may be ...

  6. Cardiomyopathy

    Science.gov (United States)

    ... Rounds Seminar Series & Daily Conferences Fellowships and Residencies School of Perfusion Technology Education Resources Library & Learning Resource Center CME Resources THI Journal THI Cardiac Society Register for the Cardiac Society ...

  7. Early-Life Origins of Type 2 Diabetes: Fetal Programming of the Beta-Cell Mass

    Directory of Open Access Journals (Sweden)

    Bernard Portha

    2011-01-01

    Full Text Available A substantial body of evidence suggests that an abnormal intrauterine milieu elicited by maternal metabolic disturbances as diverse as undernutrition, placental insufficiency, diabetes or obesity, may program susceptibility in the fetus to later develop chronic degenerative diseases, such as obesity, hypertension, cardiovascular diseases and diabetes. This paper examines the developmental programming of glucose intolerance/diabetes by disturbed intrauterine metabolic condition experimentally obtained in various rodent models of maternal protein restriction, caloric restriction, overnutrition or diabetes, with a focus on the alteration of the developing beta-cell mass. In most of the cases, whatever the type of initial maternal metabolic stress, the beta-cell adaptive growth which normally occurs during gestation, does not take place in the pregnant offspring and this results in the development of gestational diabetes. Therefore gestational diabetes turns to be the ultimate insult targeting the offspring beta-cell mass and propagates diabetes risk to the next generation again. The aetiology and the transmission of spontaneous diabetes as encountered in the GK/Par rat model of type 2 diabetes, are discussed in such a perspective. This review also discusses the non-genomic mechanisms involved in the installation of the programmed effect as well as in its intergenerational transmission.

  8. Administration of Zinc plus Cyclo-(His-Pro Increases Hippocampal Neurogenesis in Rats during the Early Phase of Streptozotocin-Induced Diabetes

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    Bo Young Choi

    2017-01-01

    Full Text Available The effects of zinc supplementation on hippocampal neurogenesis in diabetes mellitus have not been studied. Herein, we investigated the effects of zinc plus cyclo-(His-Pro (ZC on neurogenesis occurring in the subgranular zone of dentate gyrus after streptozotocin (STZ-induced diabetes. ZC (27 mg/kg was administered by gavage once daily for one or six weeks from the third day after the STZ injection, and histological evaluation was performed at 10 (early phase or 45 (late phase days after STZ injection. We found that the proliferation of progenitor cells in STZ-induced diabetic rats showed an increase in the early phase. Additionally, ZC treatment remarkably increased the number of neural progenitor cells (NPCs and immature neurons in the early phase of STZ-induced diabetic rats. Furthermore, ZC treatment showed increased survival rate of newly generated cells but no difference in the level of neurogenesis in the late phase of STZ-induced diabetic rats. The present study demonstrates that zinc supplementation by ZC increases both NPCs proliferation and neuroblast production at the early phase of diabetes. Thus, this study suggests that zinc supplemented with a histidine/proline complex may have beneficial effects on neurogenesis in patients experiencing the early phase of Type 1 diabetes.

  9. Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Posafalvi, Anna; van den Berg, Maarten P.; Hilfiker-Kleiner, Denise; Bollen, Ilse A. E.; Sliwa, Karen; Alders, Marielle; AlMomani, Rowida; van Langen, Irene M.; van der Meer, Peter; Sinke, Richard J.; van der Velden, Jolanda; Van Veldhuisen, Dirk J.; van Tintelen, J. Peter; Jongbloed, Jan D. H.

    2014-01-01

    Aim Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM. Methods and results We collected 18 families with PPCM and DCM cases from various countries. We studied

  10. Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Posafalvi, Anna; van den Berg, Maarten P.; Hilfiker-Kleiner, Denise; Bollen, Ilse A. E.; Sliwa, Karen; Alders, Mariëlle; Almomani, Rowida; van Langen, Irene M.; van der Meer, Peter; Sinke, Richard J.; van der Velden, Jolanda; van Veldhuisen, Dirk J.; van Tintelen, J. Peter; Jongbloed, Jan D. H.

    2014-01-01

    Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM. We collected 18 families with PPCM and DCM cases from various countries. We studied the clinical

  11. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

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    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  12. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Science.gov (United States)

    Gürke, Jacqueline; Hirche, Frank; Thieme, René; Haucke, Elisa; Schindler, Maria; Stangl, Gabriele I; Fischer, Bernd; Navarrete Santos, Anne

    2015-01-01

    During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

  13. Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.

    Directory of Open Access Journals (Sweden)

    Jacqueline Gürke

    Full Text Available During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2, branched chain ketoacid dehydrogenase (Bckdha and dehydrolipoyl dehydrogenase (Dld, were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.

  14. Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

    Science.gov (United States)

    Sokup, Alina; Góralczyk, Barbara; Góralczyk, Krzysztof; Rość, Danuta

    2012-02-01

    To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. Prospective postpregnancy cohort study. Polish university hospitals. Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. All women were studied 2-24 months (mean 12 ± 10 months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels. Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83 mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high-sensitivity C-reactive protein and triglyceride/high-density lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E-selectin was independently associated with triglyceride levels. Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2-24 months after an index pregnancy. Normalization of

  15. Diabetes and early postpartum methicillin-resistant Staphylococcus aureus infection in US hospitals

    NARCIS (Netherlands)

    Parriott, Andrea M.; Arah, Onyebuchi A.

    2013-01-01

    The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) infection in postpartum women is not well characterized. Because diabetes is a risk factor for some infections, we sought to characterize the relationship between diabetes and invasive MRSA infections in women admitted to US

  16. Prevention of early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    Czech Academy of Sciences Publication Activity Database

    Funda, David P.; Fundová, Petra; Hansen, A. K.; Buschard, K.

    2014-01-01

    Roč. 9, č. 4 (2014) E-ISSN 1932-6203 R&D Projects: GA ČR GA310/09/1640; GA MZd(CZ) NS10340 Institutional support: RVO:61388971 Keywords : gliadin * diabetes * diabetes 1 type * NOD mice Subject RIV: EC - Immunology Impact factor: 3.234, year: 2014

  17. Increased maternal plasma leptin in early pregnancy and risk of gestational diabetes mellitus.

    Science.gov (United States)

    Qiu, Chunfang; Williams, Michelle A; Vadachkoria, Surab; Frederick, Ihunnaya O; Luthy, David A

    2004-03-01

    Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk. Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals. GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. II-2

  18. Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria--possible effect of early antihypertensive treatment during pregnancy

    DEFF Research Database (Denmark)

    Nielsen, L R; Kragh-Müller, Claus; Damm, P

    2006-01-01

    In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine...... treatment in the prevalence of preterm delivery....... was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive...

  19. Reduced prevalence of early preterm delivery in women with Type 1 diabetes and microalbuminuria--possible effect of early antihypertensive treatment during pregnancy

    DEFF Research Database (Denmark)

    Nielsen, L R; Kragh-Müller, Claus; Damm, P

    2006-01-01

    In normotensive women with Type 1 diabetes and microalbuminuria we previously found preterm delivery (pregnancies. Antihypertensive treatment was initiated in late pregnancy when preeclampsia was diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine...... was changed and early antihypertensive treatment with methyldopa was initiated if antihypertensive treatment was given prior to pregnancy, if urinary albumin excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present study describes the impact of this more aggressive antiypertensive...

  20. Clinical-radiological experiences in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, A; Bonse, G; Beck, B; Sauter, E; Sundermeyer, R; Gunkel, L V

    1986-09-01

    The hypertrophic cardiomyopathy shows a series of interesting clinical and radiological problems, discussed in case of selected patients. A special difficult problem arises in the differential diagnosis of hypertrophic cardiomyopathy and cardiac disease secondary to systemic hypertension.

  1. Frequency and clinical genetics of familial dilated cardiomyopathy in ...

    African Journals Online (AJOL)

    Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: Implications for the evaluation of patients with unexplained cardiomyopathy. NBA Ntusi, A Wonkam, G Shaboodien, M Badri, BM Mayosi ...

  2. Pilot Study of an Individualised Early Postpartum Intervention to Increase Physical Activity in Women with Previous Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Harold David McIntyre

    2012-01-01

    Full Text Available Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined. We report a pilot study of a convenient, home based exercise program with telephone support, suited to the early post-partum period. Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week randomised controlled trial of Usual Care (n=13 versus Supported Care (individualised exercise program with regular telephone support; n=15. Baseline characteristics (Mean ± SD were: Age  33±4  years; Weight 80 ± 20 kg and Body Mass Index (BMI 30.0±9.7 kg/m2. The primary outcome, planned physical activity {Median (Range}, increased by 60 (0–540 mins/week in the SC group versus 0 (0–580 mins/week in the UC group (P=0.234. Walking was the predominant physical activity. Body weight, BMI, waist circumference, % body fat, fasting glucose and insulin did not change significantly over time in either group. This intervention designed to increase physical activity in post-partum women with previous gestational diabetes proved feasible. However, no measurable improvement in metabolic or biometric parameters was observed over a three month period.

  3. Chitosan-based dressings loaded with neurotensin--an efficient strategy to improve early diabetic wound healing.

    Science.gov (United States)

    Moura, Liane I F; Dias, Ana M A; Leal, Ermelindo C; Carvalho, Lina; de Sousa, Hermínio C; Carvalho, Eugénia

    2014-02-01

    One important complication of diabetes mellitus is chronic, non-healing diabetic foot ulcers (DFUs). This study aims to develop and use dressings based on chitosan derivatives for the sustained delivery of neurotensin (NT), a neuropeptide that acts as an inflammatory modulator in wound healing. Three different derivatives, namely N-carboxymethyl chitosan, 5-methyl pyrrolidinone chitosan (MPC) and N-succinyl chitosan, are presented as potential biomaterials for wound healing applications. Our results show that MPC has the best fluid handling capacity and delivery profile, also being non-toxic to Raw 264.7 and HaCaT cells. NT-loaded and non-loaded MPC dressings were applied to control/diabetic wounds to evaluate their in vitro/in vivo performance. The results show that the former induced more rapid healing (50% wound area reduction) in the early phases of wound healing in diabetic mice. A NT-loaded MPC foam also reduced expression of the inflammatory cytokine TNF-α (Pdiabetic skin (P<0.001), significantly increasing fibroblast migration and collagen (COL1A1, COL1A2 and COL3A1) expression and deposition. These results suggest that MPC-based dressings may work as an effective support for sustained NT release to reduce DFUs. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene.

    Science.gov (United States)

    Ripoll-Vera, Tomás; Gámez, José María; Govea, Nancy; Gómez, Yolanda; Núñez, Juana; Socías, Lorenzo; Escandell, Ángela; Rosell, Jorge

    2016-02-01

    Mutations in the troponin T gene (TTNT2) have been associated in small studies with the development of hypertrophic cardiomyopathy characterized by a high risk of sudden death and mild hypertrophy. We describe the clinical course of patients carrying mutations in this gene. We analyzed the clinical characteristics and prognosis of patients with mutations in the TNNT2 gene who were seen in an inherited cardiac disease unit. Of 180 families with genetically studied cardiomyopathies, 21 families (11.7%) were identified as having mutations in TNNT2: 10 families had Arg92Gln, 5 had Arg286His, 3 had Arg278Cys, 1 had Arg92Trp, 1 had Arg94His, and 1 had Ile221Thr. Thirty-three additional genetic carriers were identified through family assessment. The study included 54 genetic carriers: 56% were male, and the mean average age was 41 ± 17 years. There were 33 cases of hypertrophic cardiomyopathy, 9 of dilated cardiomyopathy, and 1 of noncompaction cardiomyopathy, and maximal myocardial thickness was 18.5 ± 6mm. Ventricular dysfunction was present in 30% of individuals and a history of sudden death in 62%. During follow-up, 4 patients died and 14 (33%) received a defibrillator (8 probands, 6 relatives). Mean survival was 54 years. Carriers of Arg92Gln had early disease development, high penetrance, a high risk of sudden death, a high rate of defibrillator implantation, and a high frequency of mixed phenotype. Mutations in the TNNT2 gene were more common in this series than in previous studies. The clinical and prognostic profiles depended on the mutation present. Carriers of the Arg92Gln mutation developed hypertrophic or dilated cardiomyopathy and had a significantly worse prognosis than those with other mutations in TNNT2 or other sarcomeric genes. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  5. Alterations in retinal nerve fiber layer thickness in early stages of diabetic retinopathy and potential risk factors.

    Science.gov (United States)

    Shi, Rui; Guo, Zhonglan; Wang, Feng; Li, Rong; Zhao, Lei; Lin, Rong

    2018-02-01

    To investigate the loss of retinal nerve fiber layer (RNFL) in type-2 diabetic patients with early-stage diabetic retinopathy (DR) and to identify potential risk factors accounting for these alterations. In this cross-sectional study, 158 type-2 diabetic patients were divided into three groups based on their DR status. RNFL thickness and other optic disc parameters were obtained by optical coherence tomography (OCT) and then compared among different groups. We investigated the potential association between RNFL loss and systemic risk factors for DR, including diabetes duration, body mass index (BMI), serum lipids, hemoglobin A1c (HbA1c) and albumin-creatinine ratio (ACR). One-way ANOVA was carried out to compare RNFL thickness among different groups, Pearson correlation and multivariate linear regression analysis were performed to determine potential risk factors related to RNFL thickness in these patients. There were significant differences in the average (F = 8.872, P = 0.003), superior (F = 8.769, P = 0.004), and inferior (F = 8.857, P = 0.003) RNFL thickness of both eyes among the groups, but no obvious difference in optic disc parameters was found. Diabetic duration, BMI, TG, High density lipoprotein cholesterol (HDL), HbA1c, and ACR were found negatively related to the RNFL thickness in both or single eye according to Pearson correlation analysis. After controlling for age, gender, and axis length (AL) in multivariate linear regression analysis, the diabetic duration was associated significantly with RNFL thickness of superior in both eye (right eye: p = 0.016, left eye: p = 0.024), BMI was related to the nasal quadrant of the right eye (p = 0.034), and TG was related to the inferior of the right eye (p = 0.037), HbA1c (p = 0.026) was associated significantly with the average RNFL thickness of the right eye. In addition, ACR was found negatively related to average (p = 0.042) and inferior quadrant (p = 0.014) of the left eye

  6. Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism.

    Science.gov (United States)

    Mahmoud, Ayman M; Abd El-Twab, Sanaa M; Abdel-Reheim, Eman S

    2017-06-01

    Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated. Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks. Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina. These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

  7. Exercise as a provocative test in early renal disease in type 1 (insulin-dependent) diabetes

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, B; Baker, L; Deckert, T

    1985-01-01

    micrograms/min) and 14 Albustix-negative diabetics (group 2) with increased urinary albumin excretion (15-122 micrograms/min). Assignment to a study group was made on the basis of three 24-h urine collections, and the groups were well matched for age, weight, height, and serum creatinine concentration....... The two diabetic groups were similar with regard to duration of disease (13 +/- 6 versus 16 +/- 3 years), metabolic control (HbA1c: 8.4 +/- 1.4 versus 8.7 +/- 1.3%) and degree of diabetic complications (beat-to-beat variation and retinopathy). An exercise protocol of 450 and 600 kpm/min workloads...

  8. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kodera, Ryo, E-mail: kodera@cc.okayama-u.ac.jp [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Shikata, Kenichi [Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Usui, Hitomi Kataoka [Department of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan); Makino, Hirofumi [Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558 (Japan)

    2014-01-17

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose.

  9. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-inflammatory action in a rat model of type 1 diabetes

    International Nuclear Information System (INIS)

    Kodera, Ryo; Shikata, Kenichi; Takatsuka, Tetsuharu; Oda, Kaori; Miyamoto, Satoshi; Kajitani, Nobuo; Hirota, Daisho; Ono, Tetsuichiro; Usui, Hitomi Kataoka; Makino, Hirofumi

    2014-01-01

    Highlights: •DPP-4 inhibitor decreased urinary albumin excretion in a rat of type 1 diabetes. •DPP-4 inhibitor ameliorated histlogical changes of diabetic nephropathy. •DPP-4 inhibitor has reno-protective effects through anti-inflammatory action. •DPP-4 inhibitor is beneficial on diabetic nephropathy besides lowering blood glucose. -- Abstract: Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors are incretin-based drugs in patients with type 2 diabetes. In our previous study, we showed that glucagon-like peptide-1 (GLP-1) receptor agonist has reno-protective effects through anti-inflammatory action. The mechanism of action of DPP-4 inhibitor is different from that of GLP-1 receptor agonists. It is not obvious whether DPP-4 inhibitor prevents the exacerbation of diabetic nephropathy through anti-inflammatory effects besides lowering blood glucose or not. The purpose of this study is to clarify the reno-protective effects of DPP-4 inhibitor through anti-inflammatory actions in the early diabetic nephropathy. Materials and methods: Five-week-old male Sprague–Dawley (SD) rats were divided into three groups; non-diabetes, diabetes and diabetes treated with DPP-4 inhibitor (PKF275-055; 3 mg/kg/day). PKF275-055 was administered orally for 8 weeks. Results: PKF275-055 increased the serum active GLP-1 concentration and the production of urinary cyclic AMP. PKF275-055 decreased urinary albumin excretion and ameliorated histological change of diabetic nephropathy. Macrophage infiltration was inhibited, and inflammatory molecules were down-regulated by PKF275-055 in the glomeruli. In addition, nuclear factor-κB (NF-κB) activity was suppressed in the kidney. Conclusions: These results indicate that DPP-4 inhibitor, PKF275-055, have reno-protective effects through anti-inflammatory action in the early stage of diabetic nephropathy. The endogenous biological active GLP-1 might be beneficial on diabetic nephropathy besides lowering blood glucose

  10. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

    Directory of Open Access Journals (Sweden)

    Mehdi Peighambari

    2012-09-01

    Full Text Available Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  11. Role of Nutritional Factors at the Early Life Stages in the Pathogenesis and Clinical Course of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Yukiko Kagohashi

    2015-01-01

    Full Text Available Nutrition has been suggested as an important environmental factor other than viruses and chemicals in the pathogenesis of type 1 diabetes (T1D. Whereas various maternal dietary nutritional elements have been suggested and examined in T1D of both humans and experimental animals, the results largely remain controversial. In a series of studies using T1D model nonobese diabetic (NOD mice, maternal dietary n-6/n-3 essential fatty acid ratio during pregnancy and lactation period, that is, early life stages of the offspring, has been shown to affect pathogenesis of insulitis and strongly prevent overt T1D of the offspring, which is consistent with its preventive effects on other allergic diseases.

  12. Metabolic imaging of patients with cardiomyopathy

    International Nuclear Information System (INIS)

    Geltman, E.M.

    1991-01-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies

  13. Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes

    NARCIS (Netherlands)

    Kim, Yu-Sok; Immink, Rogier V.; Stok, Wim J.; Karemaker, John M.; Secher, Niels H.; van Lieshout, Johannes J.

    2008-01-01

    Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and cardiovascular autonomic neuropathy may affect cerebral autoregulation. In the present study, we tested the

  14. An improved early detection method of type-2 diabetes mellitus using multiple classifier system

    KAUST Repository

    Zhu, Jia; Xie, Qing; Zheng, Kai

    2015-01-01

    The specific causes of complex diseases such as Type-2 Diabetes Mellitus (T2DM) have not yet been identified. Nevertheless, many medical science researchers believe that complex diseases are caused by a combination of genetic, environmental

  15. Subaortic membrane mimicking hypertrophic cardiomyopathy.

    Science.gov (United States)

    Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

    2015-11-04

    A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. 2015 BMJ Publishing Group Ltd.

  16. Cardiac MRI in restrictive cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Singh Gulati, G., E-mail: gulatigurpreet@rediffmail.com [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Seth, S. [Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India); Sharma, S. [Department of Cardiovascular Radiology, All India Institute of Medical Sciences, Ansari Nagar, Delhi (India)

    2012-02-15

    Restrictive cardiomyopathy (RCM) is a specific group of heart muscle disorders characterized by inadequate ventricular relaxation during diastole. This leads to diastolic dysfunction with relative preservation of systolic function. Although short axis systolic function is usually preserved in RCM, the long axis systolic function may be severely impaired. Confirmation of diagnosis and information regarding aetiology, extent of myocardial damage, and response to treatment requires imaging. Importantly, differentiation from constrictive pericarditis (CCP) is needed, as only the latter is managed surgically. Echocardiography is the initial cardiac imaging technique but cannot reliably suggest a tissue diagnosis; although recent advances, especially tissue Doppler imaging and spectral tracking, have improved its ability to differentiate RCM from CCP. Cardiac catheterization is the reference standard, but is invasive, two-dimensional, and does not aid myocardial characterization. Cardiac magnetic resonance (CMR) is a versatile technique providing anatomical, morphological and functional information. In recent years, it has been shown to provide important information regarding disease mechanisms, and also been found useful to guide treatment, assess its outcome and predict patient prognosis. This review describes the CMR features of RCM, appearances in various diseases, its overall role in patient management, and how it compares with other imaging techniques.

  17. Fractalkine in human inflammatory cardiomyopathy.

    Science.gov (United States)

    Escher, F; Vetter, R; Kühl, U; Westermann, D; Schultheiss, H-P; Tschöpe, C

    2011-05-01

    Cardiac inflammation is important for the prognosis of patients with inflammatory cardiomyopathy (CMi), but the mechanisms leading to it are not fully elucidated. To study the role of fractalkine (CX3CL1) in chemotactic and adhesive properties of peripheral blood mononuclear cells (PBMCs) in patients with CMi. Patients with enterovirus (EV)-positive CMi, patients with virus-negative CMi, patients with parvovirus B19 (B19) genomes with low intramyocardial inflammation and patients without cardiac inflammation and viral infection in the endomyocardial biopsy (EMB) were enrolled (n=10/group). The expression of CX3CL1 and monocyte chemoattractant protein (MCP-1) in EMBs was significantly increased in EV-positive and virus-negative patients with CMi in contrast to controls and B19-positive patients (EV+ vs controls: CX3CL1-area fraction (AF) % 0.078±0.012 vs 0.009±0.003 pattenuated positive chronotropic response to β-adrenergic stimulation with isoproterenol. The cardiac and plasma CX3CL1/CX3CR1 system is upregulated in CMi and this affects the functional potential of PBMCs. Moreover, a direct cardiodepressive effect of CX3CL1 in cardiac tissue was demonstrated since neonatal cardiomyocytes exhibited an attenuated positive chronotropic response to β-adrenergic stimulation.

  18. Effect of chicory seed extract on glucose tolerance test (GTT and metabolic profile in early and late stage diabetic rats

    Directory of Open Access Journals (Sweden)

    Ali Ahadi

    2012-10-01

    Full Text Available Background and purpose of the study The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT and blood biochemical indices of experimentally-induced hyperglycemic rats.MethodsLate stage and early stage of Type 2 diabetes mellitus (T2DM were induced in rats by streptozotocin (STZ and a combination of STZ and niacinamide (NIA/STZ, respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days. Body weight and fasting blood sugar (FBS were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c and sera for alanine aminotransferase (ALT, aspartate aminotransferase (AST, nitric oxide (NO, triacylglycerol (TG, total cholesterol (TC, total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days.ResultsDuring 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05. Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated earlystage diabetic rats.ConclusionsChicory appeared to have short-term (about 2 hours, as far as GTT is concerned and longterm (28 days, in this study effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.

  19. Pathogenesis and prevention of type 2 diabetes: parental determinants, breastfeeding, and early childhood nutrition.

    Science.gov (United States)

    Bartz, Sarah; Freemark, Michael

    2012-02-01

    Among the factors predisposing to type 2 diabetes in children, adolescents, and young adults, the health and behavior of both the mother and father are critical. Prevention and treatment of parental nutritional disorders (including obesity and malnutrition), promotion of breastfeeding, and avoidance of overfeeding of young children are essential for childhood health and metabolic function. Focusing research and policy on parental influences on childhood health should reduce the risks of obesity and type 2 diabetes in future generations.

  20. Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Immanuel, Jincy; Simmons, David

    2017-10-02

    We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

  1. Early diagnostic predictors: useful in treatment and progression of diabetes associated nephropathy

    International Nuclear Information System (INIS)

    Nawab, S.N.; Shahid, S.M.; Azhar, A.; Ahmed, N.

    2013-01-01

    Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes mellitus (T2DM) characterized by frequent microalbuminuria, elevated arterial blood pressure, persistent decline in glomerular filtration rate and high risk of morbidity and mortality. It encompasses long-term duration of diabetes, which has an effect on the minute blood vessels of kidney. The biochemical parameters play a key role in the prediction of nephropathy in T2DM patients. Therefore, the present study was conducted to investigate the role of biochemical markers in the prediction of DN in T2DM patients. The aim of this study was addressed in case-control setting, 230 T2DM, 200 DN patients and 110 non diabetic healthy individuals were included in order to assess the biochemical parameters and risk of DN. Patients were recruited according to WHO's criteria from various hospitals of Karachi, Pakistan. After getting informed consent from patients and control subjects, clinical data was recorded. Five hundred and forty (n=540) samples were studied for their serum blood glucose, blood pressure, glycosylated hemoglobin (HbAlc), serum creatinine, serum urea, lipid profile and urinary albumin levels. The analysis showed that incidence and the progression of the DN increased with hyperglycemia, longer duration of diabetes, dyslipidemia, elevated level of serum urea, creatinine and urinary albumin levels in patients with T2DM. Therefore, these biochemical predictors can anticipate the occurrence of nephropathy in later stages of diabetes. (author)

  2. An automated retinal imaging method for the early diagnosis of diabetic retinopathy.

    Science.gov (United States)

    Franklin, S Wilfred; Rajan, S Edward

    2013-01-01

    Diabetic retinopathy is a microvascular complication of long-term diabetes and is the major cause for eyesight loss due to changes in blood vessels of the retina. Major vision loss due to diabetic retinopathy is highly preventable with regular screening and timely intervention at the earlier stages. Retinal blood vessel segmentation methods help to identify the successive stages of such sight threatening diseases like diabetes. To develop and test a novel retinal imaging method which segments the blood vessels automatically from retinal images, which helps the ophthalmologists in the diagnosis and follow-up of diabetic retinopathy. This method segments each image pixel as vessel or nonvessel, which in turn, used for automatic recognition of the vasculature in retinal images. Retinal blood vessels were identified by means of a multilayer perceptron neural network, for which the inputs were derived from the Gabor and moment invariants-based features. Back propagation algorithm, which provides an efficient technique to change the weights in a feed forward network, is utilized in our method. Quantitative results of sensitivity, specificity and predictive values were obtained in our method and the measured accuracy of our segmentation algorithm was 95.3%, which is better than that presented by state-of-the-art approaches. The evaluation procedure used and the demonstrated effectiveness of our automated retinal imaging method proves itself as the most powerful tool to diagnose diabetic retinopathy in the earlier stages.

  3. Early diagnostic predictors: useful in treatment and progression of diabetes associated nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nawab, S. N.; Shahid, S. M.; Azhar, A. [University of Karachi, Karachi (Pakistan). Dept. of Biotechnology and Genetic Engineering; Ahmed, N. [University of Karachi, Karachi (Pakistan). Dept. of Biochemistry

    2013-06-15

    Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes mellitus (T2DM) characterized by frequent microalbuminuria, elevated arterial blood pressure, persistent decline in glomerular filtration rate and high risk of morbidity and mortality. It encompasses long-term duration of diabetes, which has an effect on the minute blood vessels of kidney. The biochemical parameters play a key role in the prediction of nephropathy in T2DM patients. Therefore, the present study was conducted to investigate the role of biochemical markers in the prediction of DN in T2DM patients. The aim of this study was addressed in case-control setting, 230 T2DM, 200 DN patients and 110 non diabetic healthy individuals were included in order to assess the biochemical parameters and risk of DN. Patients were recruited according to WHO's criteria from various hospitals of Karachi, Pakistan. After getting informed consent from patients and control subjects, clinical data was recorded. Five hundred and forty (n=540) samples were studied for their serum blood glucose, blood pressure, glycosylated hemoglobin (HbAlc), serum creatinine, serum urea, lipid profile and urinary albumin levels. The analysis showed that incidence and the progression of the DN increased with hyperglycemia, longer duration of diabetes, dyslipidemia, elevated level of serum urea, creatinine and urinary albumin levels in patients with T2DM. Therefore, these biochemical predictors can anticipate the occurrence of nephropathy in later stages of diabetes. (author)

  4. Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1% was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-% served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

  5. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Schievink, B; Kröpelin, T; Mulder, S

    2016-01-01

    AIMS: To develop and validate a model to simulate progression of diabetic kidney disease (DKD) from early onset until end-stage renal disease (ESRD), and to assess the effect of renin-angiotensin system (RAS) intervention in early, intermediate and advanced stages of DKD. METHODS: We used data from...

  6. Detecting intrinsic muscle weakness of the hallux as an addition to early-stage screening of the feet in patients with diabetes

    NARCIS (Netherlands)

    Mahieu, R.; Coenen, M. N. O.; van Bemmel, T.; van der Zaag-Loonen, H. J.; Theuvenet, W. J.

    Aims: Present-day screening of the diabetic foot involves the Semmes Weinstein Monofilament Test for evaluating loss of sensibility, while testing for intrinsic muscle weakness is not implied. Just as with the early detection of sensibility loss, early detection of intrinsic muscle weakness might

  7. Development of an IoT early-warning temperature home-monitoring system for diabetic foot ulcer-or Charcot-feet patients

    DEFF Research Database (Denmark)

    Dittmann, Lars; Petersen, Martin Nordal; Yderstræde, Knud Bonnet

    2017-01-01

    In severe cases, diabetic patients can develop ulcers at the feet and lower leg regions.This,together with a condition called Charcot-foot, can lead to severe wounds, numbness and eventually amputation. There are ways to treat the condition, but the key element is early-warning and early treatment....

  8. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy and infiltrative cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Rebecca Schofield

    2016-11-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common inherited cardiac disease. Cardiac imaging plays a key role in the diagnosis and management, with cardiovascular magnetic resonance (CMR an important modality. CMR provides a number of different techniques in one examination: structure and function, flow imaging and tissue characterisation particularly with the late gadolinium enhancement (LGE technique. Other techniques include vasodilator perfusion, mapping (especially T1 mapping and extracellular volume quantification [ECV] and diffusion-weighted imaging with its potential to detect disarray. Clinically, the uses of CMR are diverse. The imaging must be considered within the context of work-up, particularly the personal and family history, Electrocardiogram (ECG and echocardiogram findings. Subtle markers of possible HCM can be identified in genotype positive left ventricular hypertrophy (LVH-negative subjects. CMR has particular advantages for assessment of the left ventricle (LV apex and is able to detect both missed LVH (apical and basal antero-septum, when the echocardiography is normal but the ECG abnormal. CMR is important in distinguishing HCM from both common phenocopies (hypertensive heart disease, athletic adaptation, ageing related changes and rarer pheno and/or genocopies such as Fabry disease and amyloidosis. For these, in particular the LGE technique and T1 mapping are very useful with a low T1 in Fabry’s, and high T1 and very high ECV in amyloidosis. Moreover, the tissue characterisation that is possible using CMR offers a potential role in patient risk stratification, as scar is a very strong predictor of future heart failure. Scar may also play a role in the prediction of sudden death. CMR is helpful in follow-up assessment, especially after septal alcohol ablation and myomectomy.

  9. Gfr estimation using 99mTc DTPA gates method for assessment of early diabetic nephropathy - a comparison with 24-hour creatinine clearance

    International Nuclear Information System (INIS)

    Ghafoor, S.; Ali, M.K.; Khan, G.

    2014-01-01

    To correlate Gates glomerular filtration rate (GGFR) using technetium-99m diethylene triaminepentacetic acid (99mTc DTPA) with 24-hour creatinine clearance (CRCL) and to establish relationship with duration of diabetes in patients with early diabetic nephropathy. Study Design: A cross-sectional comparative study carried out in Nuclear Medical Centre from Aug 2009 to Jan 2010 at Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. Patients and Methods: A total of eighty three subjects were enrolled, who were divided into three groups; group 1 comprised 31 normotensive diabetics, group 2 had 37 hypertensive diabetics while group 3 had 15 normal subjects. The DTPA GFR and creatinine clearance in healthy subjects as well as diabetic patients were compared using the unpaired student's t-test. The linear association between GFR, creatinine clearance and disease duration was expressed by Pearson's correlation coefficient 'r' along with their significance levels. Results: Gates GFR showed hyperfiltration in normotensive diabetics (96.6 +- 3.3 ml/min/1.73 m/sub 2/), significantly (p<0.05) higher than controls (85.5 +- 5 ml/min/1.73 m/sub 2/), whereas hypertensive diabetics had a significantly lower (p<0.05) Gates GFR (76.8 +- 3.7) than that of controls. Significant degree of correlation existed between GGFR and CRCL in hypertensive diabetics (p<0.05, r=0.716) and controls (r=0.546). Gates GFR also showed good correlation with duration of diabetes in both diabetic groups as compared to that of CRCL. GGFR also correlated well with duration of hypertension 0.37 (0.31-0.43) as compared to CRCL 0.155 (0.15-0.16) in all groups. Conclusions: The 99mTc-DTPA clearance correlates significantly with 24-hour creatinine clearance as well as with disease duration and can provide a simple and convenient index of kidney function in patients of early diabetic nephropathy. (author)

  10. [Diagnosis and therapy of arrhythmogenic right ventricular cardiomyopathy].

    Science.gov (United States)

    Zorzi, Alessandro; Rigato, Ilaria; Migliore, Federico; Perazzolo Marra, Martina; Basso, Cristina; Thiene, Gaetano; Bauce, Barbara; Corrado, Domenico

    2014-11-01

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that predisposes to the occurrence of ventricular arrhythmias and sudden death, particularly in the young and athlete. The classic variant of the disease predominantly affects the right ventricle, but phenotypic variants with early and prevalent left ventricular involvement ("left-dominant" ARVC) have also been described, supporting the concept that arrhythmogenic cardiomyopathy is a disease of both ventricles. The diagnosis is multiparametric and is based on a series of criteria, including ECG abnormalities, arrhythmic manifestations, morpho-functional abnormalities and genetic defects. The main goal of therapy is sudden death prevention. Implant of a cardioverter-defibrillator is the most effective strategy for prevention of sudden death, but it should be reserved to selected patients after accurate risk stratification, in view of the high complication rate over a long-term follow-up, the costs and the significant psychological impact of such therapy, especially in the young individual. The other therapies (either pharmacological or not) are palliative and aimed at relieving symptoms and preventing disease progression. The definitive cure of ARVC will be based on the discovery of the molecular mechanisms that are involved in the etiology and pathogenesis of the disease.

  11. Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy: Progress and Pitfalls.

    Science.gov (United States)

    Oomen, Ad W G J; Semsarian, Christopher; Puranik, Rajesh; Sy, Raymond W

    2018-04-04

    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that predominantly affects the right ventricle. With a prevalence in the range of 1:5000 to 1:2000 persons, ARVC is one of the leading causes of sudden cardiac death in young people and in athletes. Although early detection and treatment is important, the diagnosis of ARVC remains challenging. There is no single pathognomonic diagnostic finding in ARVC; rather, current international task force criteria specify diagnostic major and minor criteria in six categories: right ventricular imaging (including echocardiography and cardiac magnetic resonance imaging (MRI)), histology, repolarisation abnormalities, depolarisation and conduction abnormalities, arrhythmias and family history (including genetic testing). Combining findings from differing diagnostic modalities can establish a "definite", "borderline" or "possible" diagnosis of ARVC. However, there are limitations inherent in the current task force criteria, including the lack of specificity for ARVC; future iterations may be improved, for example, by enhanced imaging protocols able to detect subtle changes in the structure and function of the right ventricle, incorporation of electro-anatomical data, response to adrenergic challenge, and validated criteria for interpreting genetic variants. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  12. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    Science.gov (United States)

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  13. Controversies Surrounding Exercise in Genetic Cardiomyopathies.

    Science.gov (United States)

    Atteya, Gourg; Lampert, Rachel

    2018-04-01

    Exercise and sports are an integral part of daily life for millions of Americans, with 16% of the US population older than age 15 years engaged in sports or exercise activities (Bureau of Labor statistics). The physical and psychological benefits of exercise are well-recognized. However, high-profile cases of athletes dying suddenly on the field, often due to undiagnosed genetic cardiomyopathies, raise questions about the risks and benefits of exercise for those with cardiomyopathy. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. [Early invasive strategy in diabetic patients with non-ST-segment elevation acute coronary syndromes].

    Science.gov (United States)

    Baeza Román, Anna; Latour Pérez, Jaime; de Miguel Balsa, Eva; Pino Izquierdo, Karel; Coves Orts, Francisco Javier; García Ochando, Luis; de la Torre Fernández, Maria José

    2014-05-20

    In the management of non-ST-segment elevation acute coronary syndromes (NSTE-ACS), several studies have shown a reduction in mortality with the use of an invasive strategy in high-risk patients, including diabetic patients. Paradoxically, other studies have shown an under-utilization of this invasive strategy in these patients. The aim of this study is to determine the characteristics of patients managed conservatively and identify determinants of the use of invasive or conservative strategy. Retrospective cohort study conducted in diabetic patients with NSTE-ACS included in the ARIAM-SEMICYUC registry (n=531) in 2010 and 2011. We performed crude and adjusted unconditional logistic regression. We analyzed 531 diabetic patients, 264 (49.7%) of which received invasive strategy. Patients managed conservatively were a subgroup characterized by older age and cardiovascular comorbidity, increased risk of bleeding and the absence of high-risk electrocardiogram (ECG). In diabetic patients with NSTE-ACS, independent predictors associated with conservative strategy were low-risk ECG, initial Killip class>1, high risk of bleeding and pretreatment with clopidogrel. The fear of bleeding complications or advanced coronary lesions could be the cause of the underutilization of an invasive strategy in diabetic patients with NSTE-ACS. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  15. Role of glucagon in intestinal hyperemia associated with early experimental diabetes mellitus

    International Nuclear Information System (INIS)

    Yrle, L.F.; Smith, J.K.; Benoit, J.N.; Granger, D.N.; Korthuis, R.J.

    1988-01-01

    The role of glucagon as a blood-borne mediator of the intestinal hyperemia associated with experimental diabetes mellitus was assessed in anesthetized fasted (18-24 h) rats 4 wk after the administration of streptozotocin or its vehicle. Selective removal of pancreatic glucagon from the circulation was accomplished by the intravenous administration of a highly specific glucagon antiserum. Blood flow to the gastrointestinal tract and kidneys was measured with radioactive microspheres using the reference sample technique. Blood flows were increased by at least 60% in each segment of the gastrointestinal tract of diabetic animals compared with control rats. Glucagon antiserum had no effect on blood flows in the gastrointestinal tract of control animals. However, the antiserum produced a significant reduction in blood flow to the stomach (26%), duodenum (25%), jejunum (12%), and kidneys (16%) in diabetic rats. There was no change in blood flow to the ileum or colon of diabetic animals with antiserum administration. The results of this study support the hypothesis that glucagon mediates a portion of the hyperemia noted in the stomach, duodenum, and jejunum. However, glucagon does not appear to play a role in the genesis of the hyperemia noted in more distal segments of the gastrointestinal tract (ileum and colon). A possible role for glucagon in the maintenance of renal blood flow in diabetic rats is suggested

  16. Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

    Science.gov (United States)

    Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

    2009-12-01

    A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

  17. Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

    Directory of Open Access Journals (Sweden)

    Akadiri Yessoufou

    2011-01-01

    Full Text Available The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life.

  18. Vitamin B1 Analog Benfotiamine Prevents Diabetes-Induced Diastolic Dysfunction and Heart Failure Through Akt/Pim-1–Mediated Survival Pathway

    Science.gov (United States)

    Katare, Rajesh G.; Caporali, Andrea; Oikawa, Atsuhiko; Meloni, Marco; Emanueli, Costanza; Madeddu, Paolo

    2010-01-01

    Background The increasing incidence of diabetes mellitus will result in a new epidemic of heart failure unless novel treatments able to halt diabetic cardiomyopathy early in its course are introduced. This study aimed to determine whether the activity of the Akt/Pim-1 signaling pathway is altered at critical stages of diabetic cardiomyopathy and whether supplementation with vitamin B1 analog benfotiamine (BFT) helps to sustain the above prosurvival mechanism, thereby preserving cardiomyocyte viability and function. Methods and Results Untreated streptozotocin-induced type 1 or leptin-receptor mutant type 2 diabetic mice showed diastolic dysfunction evolving to contractile impairment and cardiac dilatation and failure. BFT (70 mg/kg−1/d−1) improved diastolic and systolic function and prevented left ventricular end-diastolic pressure increase and chamber dilatation in both diabetic models. Moreover, BFT improved cardiac perfusion and reduced cardiomyocyte apoptosis and interstitial fibrosis. In hearts of untreated diabetic mice, the expression and activity of Akt/Pim-1 signaling declined along with O-N-acetylglucosamine modification of Akt, inhibition of pentose phosphate pathway, activation of oxidative stress, and accumulation of glycation end products. Furthermore, diabetes reduced signal transducer and activator of transcription 3 phosphorylation independently of Akt. BFT inhibited these effects of diabetes mellitus, thereby conferring cardiomyocytes with improved resistance to high glucose-induced damage. The phosphoinositide-3-kinase inhibitor LY294002 and dominant-negative Akt inhibited antiapoptotic action of BFT and Pim-1 upregulation in high glucose-challenged cardiomyocytes. Conclusions These results show that BFT protects from diabetes mellitus-induced cardiac dysfunction through pleiotropic mechanisms, culminating in the activation of prosurvival signaling pathway. Thus, BFT merits attention for application in clinical practice. PMID:20107192

  19. Vitamin B1 analog benfotiamine prevents diabetes-induced diastolic dysfunction and heart failure through Akt/Pim-1-mediated survival pathway.

    Science.gov (United States)

    Katare, Rajesh G; Caporali, Andrea; Oikawa, Atsuhiko; Meloni, Marco; Emanueli, Costanza; Madeddu, Paolo

    2010-03-01

    The increasing incidence of diabetes mellitus will result in a new epidemic of heart failure unless novel treatments able to halt diabetic cardiomyopathy early in its course are introduced. This study aimed to determine whether the activity of the Akt/Pim-1 signaling pathway is altered at critical stages of diabetic cardiomyopathy and whether supplementation with vitamin B1 analog benfotiamine (BFT) helps to sustain the above prosurvival mechanism, thereby preserving cardiomyocyte viability and function. Untreated streptozotocin-induced type 1 or leptin-receptor mutant type 2 diabetic mice showed diastolic dysfunction evolving to contractile impairment and cardiac dilatation and failure. BFT (70 mg/kg(-1)/d(-1)) improved diastolic and systolic function and prevented left ventricular end-diastolic pressure increase and chamber dilatation in both diabetic models. Moreover, BFT improved cardiac perfusion and reduced cardiomyocyte apoptosis and interstitial fibrosis. In hearts of untreated diabetic mice, the expression and activity of Akt/Pim-1 signaling declined along with O-N-acetylglucosamine modification of Akt, inhibition of pentose phosphate pathway, activation of oxidative stress, and accumulation of glycation end products. Furthermore, diabetes reduced pSTAT3 independently of Akt. BFT inhibited these effects of diabetes mellitus, thereby conferring cardiomyocytes with improved resistance to high glucose-induced damage. The phosphoinositide-3-kinase inhibitor LY294002 and dominant-negative Akt inhibited antiapoptotic action of BFT-induced and Pim-1 upregulation in high glucose-challenged cardiomyocytes. These results show that BFT protects from diabetes mellitus-induced cardiac dysfunction through pleiotropic mechanisms, culminating in the activation of prosurvival signaling pathway. Thus, BFT merits attention for application in clinical practice.

  20. Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Klaassen, J.K.

    1986-01-01

    Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of ( 125 I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred

  1. Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

    Science.gov (United States)

    Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

    2015-10-01

    Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

  2. Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial.

    Science.gov (United States)

    Simmons, David; Hague, William M; Teede, Helena J; Cheung, N Wah; Hibbert, Emily J; Nolan, Christopher J; Peek, Michael J; Girosi, Federico; Cowell, Christopher T; Wong, Vincent W-M; Flack, Jeff R; McLean, Mark; Dalal, Raiyomand; Robertson, Annette; Rajagopal, Rohit

    2018-05-28

    Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.

  3. Dynamic cerebral autoregulatory capacity is affected early in Type 2 diabetes

    DEFF Research Database (Denmark)

    Kim, Y.S.; Immink, R.V.; Stok, W.J.

    2008-01-01

    Type 2 diabetes is associated with an increased risk of endothelial dysfunction and microvascular complications with impaired autoregulation of tissue perfusion. Both microvascular disease and cardiovascular autonomic neuropathy may affect cerebral autoregulation. In the present study, we tested...... the hypothesis that, in the absence of cardiovascular autonomic neuropathy, cerebral autoregulation is impaired in subjects with DM+ (Type 2 diabetes with microvascular complications) but intact in subjects with DM- (Type 2 diabetes without microvascular complications). Dynamic cerebral autoregulation...... and the steady-state cerebrovascular response to postural change were studied in subjects with DM+ and DM-, in the absence of cardiovascular autonomic neuropathy, and in CTRL (healthy control) subjects. The relationship between spontaneous changes in MCA V(mean) (middle cerebral artery mean blood velocity...

  4. Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases.

    Science.gov (United States)

    Martin, M W S; Stafford Johnson, M J; Celona, B

    2009-01-01

    To review the clinical and diagnostic findings and survival of dilated cardiomyopathy from a large population of dogs in England. A retrospective study of the case records of dogs with dilated cardiomyopathy collected between January 1993 and May 2006. There were 369 dogs with dilated cardiomyopathy of which all were pure-bred dogs except for four. The most commonly affected breeds were dobermanns and boxers. Over 95 per cent of dogs weighed more than 15 kg and 73 per cent were male. The median duration of signs before referral was three weeks with 65 per cent presenting in stage 3 heart failure. The most common signs were breathlessness (67 per cent) and coughing (64 per cent). The majority of dogs (89 per cent) had an arrhythmia at presentation and 74 per cent of dogs had radiographic signs of pulmonary oedema or pleural effusion. The median survival time was 19 weeks. Dilated cardiomyopathy occurs primarily in medium to large breed pure-bred dogs, and males are more frequently affected than females. The duration of clinical signs before referral is often short and the survival times are poor. Greater awareness of affected breeds, clinical signs and diagnostic findings may help in early recognition of this disease which often has a short clinical phase.

  5. Causes of Diabetes

    Science.gov (United States)

    ... diabetes and maturity-onset diabetes of the young (MODY). Neonatal diabetes occurs in the first 6 months of life. Doctors usually diagnose MODY during adolescence or early adulthood, but sometimes the ...

  6. Segmentation of retinal blood vessels using artificial neural networks for early detection of diabetic retinopathy

    Science.gov (United States)

    Mann, Kulwinder S.; Kaur, Sukhpreet

    2017-06-01

    There are various eye diseases in the patients suffering from the diabetes which includes Diabetic Retinopathy, Glaucoma, Hypertension etc. These all are the most common sight threatening eye diseases due to the changes in the blood vessel structure. The proposed method using supervised methods concluded that the segmentation of the retinal blood vessels can be performed accurately using neural networks training. It uses features which include Gray level features; Moment Invariant based features, Gabor filtering, Intensity feature, Vesselness feature for feature vector computation. Then the feature vector is calculated using only the prominent features.

  7. Concomitant alteration in number and affinity of P2X and muscarinic receptors are associated with bladder dysfunction in early stage of diabetic rats.

    Science.gov (United States)

    Yoshizawa, Tsuyoshi; Hayashi, Yukio; Yoshida, Akira; Yoshida, Shohei; Ito, Yoshihiko; Yamaguchi, Kenya; Yamada, Shizuo; Takahashi, Satoru

    2018-03-01

    To investigate time course of bladder dysfunction and concurrent changes in number and affinity of the muscarinic and P 2 X receptor in the early stage of streptozotocin (STZ)-induced diabetic rats. Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle strip experiments with electrical field stimulation (EFS), carbachol, and α,β-methylene adenosine 5'-triphosphate (α,β-MeATP) were also performed at the same time-points. Additionally, concurrent changes in number and affinity of bladder muscarinic and P 2 X receptor were measured by a radioreceptor assay using [N-methyl- 3 H] scopolamine methyl chloride ([ 3 H]NMS) and α,β-methylene-ATP (2,8- 3 H) tetrasodium salt ([ 3 H]α,β-MeATP). In STZ-induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of 24-h voiding behavior from early stage. Also, the residual urine volume markedly increased in diabetic rats on cystometry. In the muscle strip experiment, the detrusor contractions induced by EFS, carbachol, and α,β-MeATP were enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the maximum number of sites (Bmax) for the specific binding of [ 3 H]NMS and [ 3 H]α,β-MeATP was concurrently increased in the bladder from diabetic rats. Increased bladder contractility is found in early stage of diabetic rats. Then, bladder dysfunction is associated with increased number of muscarinic and P 2 X receptors in STZ-induced diabetic rats.

  8. Association of hypertension and diastolic dysfunction with type-2 diabetes mellitus

    International Nuclear Information System (INIS)

    Ashraf, S.M.S.; Basir, F.

    2007-01-01

    To evaluate the prevalence of hypertension and diastolic dysfunction (LVDD) with normal ejection fraction in type-2 diabetes mellitus. Two hundred twelve diabetic patients (98 females and 114 males) from January 2005 to June 2006 were enrolled in this study. Their ages ranged from 35 to 65 years with mean age of 55 years. Patients with Diabetes Mellitus Type-2, Hypertension: BP/sup 3/140/90 (with or without medication) Body Mass Index/sub 3/30, Waist-Hip ratio>0.90. Left Ventricular Diastolic Dysfunction (LVDD) and Serum Triglyceride and HDL Cholesterol were included. Out of 212 patients, 104 (49%) were found to be hypertensive (both systolic and diastolic) and 12 patients (5.6%) were found to be suffering from isolated systolic hypertension. Hence total number of hypertensive patients was 116 (54.6%). Thirty two patients were found to be suffering from diastolic dysfunction. Hypertension and Diabetes are interlinked and show how micro and macrovascular complications of diabetes are increased when two conditions occur together. The LVDD is much more prevalent than previously suggested in patients with type-2 diabetes mellitus. Hence LVDD is an early marker of diabetic cardiomyopathy. (author)

  9. Prevalence of self-reported diagnosis of diabetes mellitus and associated risk factors in a national survey in the US population: SHIELD (Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes).

    Science.gov (United States)

    Bays, Harold E; Bazata, Debbra D; Clark, Nathaniel G; Gavin, James R; Green, Andrew J; Lewis, Sandra J; Reed, Michael L; Stewart, Walter; Chapman, Richard H; Fox, Kathleen M; Grandy, Susan

    2007-10-03

    Studies derived from continuous national surveys have shown that the prevalence of diagnosed diabetes mellitus in the US is increasing. This study estimated the prevalence in 2004 of self-reported diagnosis of diabetes and other conditions in a community-based population, using data from the Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD). The initial screening questionnaire was mailed in 2004 to a stratified random sample of 200,000 households in the US, to identify individuals, age > or = 18 years of age, with diabetes or risk factors associated with diabetes. Follow-up disease impact questionnaires were then mailed to a representative, stratified random sample of individuals (n = 22,001) in each subgroup of interest (those with diabetes or different numbers of risk factors for diabetes). Estimated national prevalence of diabetes and other conditions was calculated, and compared to prevalence estimates from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Response rates were 63.7% for the screening, and 71.8% for the follow-up baseline survey. The SHIELD screening survey found overall prevalence of self-reported diagnosis of diabetes (either type 1 or type 2) was 8.2%, with increased prevalence with increasing age and decreasing income. In logistic regression modeling, individuals were more likely to be diagnosed with type 2 diabetes if they had abdominal obesity (odds ratio [OR] = 3.50; p or =28 kg/m2 (OR = 4.04; p self-report only) to those from NHANES 1999-2002 (self-report, clinical and laboratory evaluations), the prevalence of diabetes was similar. SHIELD allows the identification of respondents with and without a current diagnosis of the illness of interest, and potential longitudinal evaluation of risk factors for future diagnosis of that illness.

  10. 2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis.

    Science.gov (United States)

    Kanter, Y; Gerson, J R; Bessman, A N

    1977-05-01

    The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA.

  11. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice : a position statement of the ESC working group on myocardial and pericardial diseases

    NARCIS (Netherlands)

    Pinto, Yigal M.; Elliott, Perry M.; Arbustini, Eloisa; Adler, Yehuda; Anastasakis, Aris; Boehm, Michael; Duboc, Denis; Gimeno, Juan; de Groote, Pascal; Imazio, Massimo; Heymans, Stephane; Klingel, Karin; Komajda, Michel; Limongelli, Giuseppe; Linhart, Ales; Mogensen, Jens; Moon, James; Pieper, Petronella G.; Seferovic, Petar M.; Schueler, Stephan; Zamorano, Jose L.; Caforio, Alida L. P.; Charron, Philippe

    2016-01-01

    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis

  12. Aortic superoxide production at the early hyperglycemic stage in a rat type 2 diabetes model and the effects of pravastatin.

    Science.gov (United States)

    Kikuchi, Chigusa; Kajikuri, Junko; Hori, Eisei; Nagami, Chie; Matsunaga, Tamihide; Kimura, Kazunori; Itoh, Takeo

    2014-01-01

    Endothelium-derived superoxide induces vascular dysfunctions. The aim of this study was to examine the activity of protein kinase C (PKC) isoforms and endothelial nitric oxide synthase (eNOS), which leads to vascular superoxide production in type 2 diabetes, in addition to the effects of pravastatin. We studied these mechanisms in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycemic stage (vs. non-diabetic Long-Evans Tokushima Otsuka [LETO] rats). Superoxide production and catalase activity were measured in aortas, as were the protein expressions of PKCδ and phospho-Ser(1177) eNOS. Superoxide production was increased in OLETF rats, and this increase was inhibited by the selective conventional PKC (cPKC) inhibitor Gö6976 and by the non-selective cPKC and novel PKC inhibitor GF109203X. Phospho-Ser(1177) eNOS was significantly increased in OLETF rats, whereas the protein expressions of PKCδ and phosopho-Thr(505) PKCδ and catalase activity were all greatly reduced. Pravastatin administration to OLETF rats in vivo had normalizing effects on all of these variables. The increment in superoxide production seen in OLETF rats (but not the production in pravastatin-treated OLETF rats) was abolished by high concentration of N(ω)-nitro-L-arginine methyl ester (electron transport inhibitor of eNOS), by sepiapterin (precursor of tetrahydrobiopterin), and by LY294002 (phosphatidylinositol 3-kinase [PI3-kinase] inhibitor). In OLETF rats at the early hyperglycemic stage, aortic superoxide production is increased owing to activation of uncoupled eNOS through phosphorylation by PI3-kinase/Akt. This may be related to the observed reduction in PKCδ/catalase activities. Pravastatin inhibited endothelial superoxide production via normalization of PKCδ/catalase activities.

  13. Early Malnutrition and Child Neurobehavioral Development: Insights from the Study of Children of Diabetic Mothers.

    Science.gov (United States)

    Rizzo, Thomas A.; And Others

    1997-01-01

    Studied whether disturbances in mothers' metabolism (N=139) during pregnancy may exert long-range effects on neurobehavioral development of singleton progeny. Examined detailed pregnancy and perinatal records of mothers who experienced diabetes in pregnancy and intelligence tests of their offspring, administered at ages 7 to 11 years. All…

  14. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

  15. Cathepsin L is crucial for the development of early experimental diabetic nephropathy

    NARCIS (Netherlands)

    Garsen, M.; Rops, A.; Dijkman, H.B.; Willemsen, B.K.; Kuppevelt, T.H. van; Russel, F.G.M.; Rabelink, T.J.; Berden, J.H.; Reinheckel, T.; Vlag, J. van der

    2016-01-01

    Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte

  16. Automated classifiers for early detection and diagnosis of retinopathy in diabetic eyes.

    Science.gov (United States)

    Somfai, Gábor Márk; Tátrai, Erika; Laurik, Lenke; Varga, Boglárka; Ölvedy, Veronika; Jiang, Hong; Wang, Jianhua; Smiddy, William E; Somogyi, Anikó; DeBuc, Delia Cabrera

    2014-04-12

    Artificial neural networks (ANNs) have been used to classify eye diseases, such as diabetic retinopathy (DR) and glaucoma. DR is the leading cause of blindness in working-age adults in the developed world. The implementation of DR diagnostic routines could be feasibly improved by the integration of structural and optical property test measurements of the retinal structure that provide important and complementary information for reaching a diagnosis. In this study, we evaluate the capability of several structural and optical features (thickness, total reflectance and fractal dimension) of various intraretinal layers extracted from optical coherence tomography images to train a Bayesian ANN to discriminate between healthy and diabetic eyes with and with no mild retinopathy. When exploring the probability as to whether the subject's eye was healthy (diagnostic condition, Test 1), we found that the structural and optical property features of the outer plexiform layer (OPL) and the complex formed by the ganglion cell and inner plexiform layers (GCL + IPL) provided the highest probability (positive predictive value (PPV) of 91% and 89%, respectively) for the proportion of patients with positive test results (healthy condition) who were correctly diagnosed (Test 1). The true negative, TP and PPV values remained stable despite the different sizes of training data sets (Test 2). The sensitivity, specificity and PPV were greater or close to 0.70 for the retinal nerve fiber layer's features, photoreceptor outer segments and retinal pigment epithelium when 23 diabetic eyes with mild retinopathy were mixed with 38 diabetic eyes with no retinopathy (Test 3). A Bayesian ANN trained on structural and optical features from optical coherence tomography data can successfully discriminate between healthy and diabetic eyes with and with no retinopathy. The fractal dimension of the OPL and the GCL + IPL complex predicted by the Bayesian radial basis function network provides better

  17. Celiac disease with pulmonary haemosiderosis and cardiomyopathy

    OpenAIRE

    Işikay, Sedat; Yilmaz, Kutluhan; Kilinç, Metin

    2012-01-01

    Celiac disease or pulmonary haemosiderosis can be associated with several distinguished conditions. Pulmonary haemosiderosis is a rare, severe and fatal disease characterised by recurrent episodes of alveolar haemorrhage, haemoptysis and anaemia. Association of pulmonary haemosiderosis and celiac disease is extremely rare. We describe a case of celiac disease presented with dilated cardiomyopathy and pulmonary haemosiderosis without gastrointestinal symptoms of celiac disease. In addition, vi...

  18. Clinical and molecular classification of cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Franco Cecchi

    2012-07-01

    Full Text Available The term “cardiomyopathies” was used for the first time 55 years ago, in 1957. Since then awareness and knowledge of this important and complex group of heart muscle diseases have improved substantially. Over these past five decades a large number of definitions, nomenclature and schemes, have been advanced by experts and consensus panel, which reflect the fast and continued advance of the scientific understanding in the field. Cardiomyopathies are a heterogeneous group of inherited myocardial diseases, which represent an important cause of disability and adverse outcome. Although considered rare diseases, the overall estimated prevalence of all cardiomyopathies is at least 3% in the general population worldwide. Furthermore, their recognition is increasing due to advances in imaging techniques and greater awareness in both the public and medical community. Cardiomyopathies represent an ideal translational model of integration between basic and clinical sciences. A multidisciplinary approach is therefore essential in order to ensure their correct diagnosis and management. In the present work, we aim to provide a concise overview of the historical background, genetic and phenotypic spectrum and evolving concepts leading to the various attempts of cardiomyopathy classifications produced over the decades.

  19. Pregnancy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Pieper, P. G.; Walker, F.

    Hypertrophic cardiomyopathy (HCM) is increasingly being diagnosed in pregnant women. Women with HCM generally tolerate pregnancy well. The risk is however higher in women who are symptomatic before pregnancy or in those with severe left ventricular outflow tract obstruction. The incidence of

  20. Tako-tsubo cardiomyopathy after a quarrel.

    African Journals Online (AJOL)

    Tako-tsubo cardiomyopathy after a quarrel. Dong-Mei Jiang1,a, Ze-Wei Sunc2,a, Jie Han2. 1. Department of Cardiology, Biomedical research (therapy) center, Sir Run Run Shaw Hospital,. College of ... acterized by (1) sudden onset of chest pain or shortness of breath; (2) ... In the present report, we de- scribe a case of ...

  1. Update in cardiomyopathies and congestive heart failure

    Directory of Open Access Journals (Sweden)

    The Heart Hospital, London, UK and Monaldi Hospital, Naples, Italy

    2012-05-01

    Full Text Available This abstract book contains four reports and all abstracts presented to the Joint Meeting: Update in cardiomyopathies and congestive heart failure, 22-23 September 2011 - Naples, Italy, endorsed by the Working Group on Myocardial and Pericardial Diseases (WG 21 of the European Society of Cardiology (ESC.

  2. Renal scintigraphy in insulin-dependent diabetes mellitus: Early glomerular and urologic dysfunction

    International Nuclear Information System (INIS)

    Poirier, J.Y.; Moisan, A.; Le Cloirec, J.; Siemen, C.; Yaouanq, J.; Edan, G.; Herry, J.Y.

    1990-01-01

    Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous injection of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-Hippuran in 115 insulin-dependent diabetic patients with albumin excretion rates (AER) less than 200 micrograms/min, and in 45 normal subjects. Separate kidney function and urinary elimination were estimated by renography. GFR was increased in the diabetic patients (152 +/- 24 ml/min/1.73 m2 vs. 128 +/- 15) and correlated significantly with RPF (r = 0.5; p less than 10(-9)). No relationship was found between GFR and the duration of diabetes, blood glucose, HbA1c, or AER. Fifty patients were hyperfiltering with RPF and filtration fraction higher than those in the normofiltering group. Slow intrarenal or pyeloureteral elimination, either unilateral or bilateral, was observed in 3 controls and 60 diabetic subjects (24 hyperfiltering; 36 normofiltering) and did not disappear with the patient in the standing position. In these 60 patients, mean age, duration of diabetes, blood glucose, HbA1c, 24 h albumin excretion rate, and frequency of peripheral or autonomic neuropathy did not differ from patients with normal scintigraphy; GFR was lower in the group with slow elimination, but not significantly so. 99mTc-DTPA renal uptake was symmetric in all the controls; asymmetric renal uptake with asymmetric GFR was observed in 13 patients (7 hyperfiltering; 6 normofiltering) and often associated with slower elimination. No evidence for renal stenotic atheroma or parenchymatous disease was found on the angiopyleoureterography. The results suggest that incipient uropathy is a very common phenomenon that occurs irrespective of glomerular dysfunction

  3. High interobserver variability in the assessment of epsilon waves : Implications for diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia

    NARCIS (Netherlands)

    Platonov, Pyotr G; Calkins, Hugh; Hauer, Richard N; Corrado, Domenico; Svendsen, Jesper H; Wichter, Thomas; Biernacka, Elżbieta Katarzyna; Saguner, Ardan M; Te Riele, Anneline S J M; Zareba, Wojciech

    BACKGROUND: Revision of the Task Force diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) has increased their sensitivity for the diagnosis of early and familial forms of the disease. The epsilon wave is a major diagnostic criterion in the context of ARVC/D,

  4. Evaluation of gestational diabetes mellitus risk factors using abdominal subcutaneous fat thickness for early pregnancy in the US imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Soo; Kim, Jung Hoon [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of); Yang, Sung Hee [Dept. of Radiology, Ilsin Christian Hospital, Busan (Korea, Republic of)

    2017-03-15

    The purpose of this study was to investigate the relationship between abdominal subcutaneous fat thickness(ASFT) and maternal gestational diabetes mellitus(GDM) measured by ultrasound at period of pregnancy. We compared maternal age, pre-pregnancy body mass index, and weight gain during pregnancy in 286 pregnant women who were diagnosed with early pregnancy ASFT and high GDM screening test(50 g OGTT) of more than 140 mg/dL. ROC curve analysis was used to determine the cut-off value of ASFT for GDM prediction. Maternal age and weight gain during pregnancy were not related to GDM in the mid-trimester and pre-pregnancy body mass index and early pregnancy ASFT were significantly different between normal and GDM high risk groups. The cut-off value of ASFT for GDM prediction was 2.23 cm(AUC 0.913. Sensitivity 76.19%, Specificity 93.72%). ASFT measured by ultrasound in early pregnancy was useful as an important index for predicting mid-trimester GDM prediction. Therefore, ASFT can be used as an auxiliary diagnostic index for early recognition of GDM.

  5. Evaluation of gestational diabetes mellitus risk factors using abdominal subcutaneous fat thickness for early pregnancy in the US imaging

    International Nuclear Information System (INIS)

    Kim, Chang Soo; Kim, Jung Hoon; Yang, Sung Hee

    2017-01-01

    The purpose of this study was to investigate the relationship between abdominal subcutaneous fat thickness(ASFT) and maternal gestational diabetes mellitus(GDM) measured by ultrasound at period of pregnancy. We compared maternal age, pre-pregnancy body mass index, and weight gain during pregnancy in 286 pregnant women who were diagnosed with early pregnancy ASFT and high GDM screening test(50 g OGTT) of more than 140 mg/dL. ROC curve analysis was used to determine the cut-off value of ASFT for GDM prediction. Maternal age and weight gain during pregnancy were not related to GDM in the mid-trimester and pre-pregnancy body mass index and early pregnancy ASFT were significantly different between normal and GDM high risk groups. The cut-off value of ASFT for GDM prediction was 2.23 cm(AUC 0.913. Sensitivity 76.19%, Specificity 93.72%). ASFT measured by ultrasound in early pregnancy was useful as an important index for predicting mid-trimester GDM prediction. Therefore, ASFT can be used as an auxiliary diagnostic index for early recognition of GDM

  6. STAT4 polymorphism is associated with early-onset type 1 diabetes, but not with late-onset type 1 diabetes.

    Science.gov (United States)

    Lee, Hye-Soon; Park, Hyewon; Yang, Seiwon; Kim, Dukhee; Park, Yongsoo

    2008-12-01

    In an effort to discover non-HLA genes affecting susceptibility to type 1 diabetes (T1D), we have investigated the association of polymorphisms in STAT4, an important signaling molecule of IL-12, gammaIFN, and IL-23, in a sample of 389 T1D patients and 152 nondiabetic controls in Korea. Four SNPs on chromosome 2q, which were recently found to be associated with rheumatoid arthritis, were examined for association and linkage disequilibrium. We found that neither alleles or genotypes among all four SNPs nor reconstructed haplotypes of the three SNPs within the same LD block (rs7574865, rs8179673, and rs10181656) were associated with susceptibility to T1D. When we stratified T1D patients into early-onset and late-onset subgroups on the basis of fewer or more than 7.8 years of age at diagnosis, however, the minor alleles of three SNPs (rs7574865, rs8179673, and rs10181656) showed a significant association with susceptibility to T1D in the early-onset subgroup (i.e., rs7574865, OR = 1.44 [1.03-2.01], P rs7574865, rs8179673, and rs10181656) showed very comparable degrees of risk for T1D. The age at diagnosis is lowest in the patients carrying the homozygotes of a minor allele, middle in the heterozygotes, and highest in the homozygotes of a major allele, suggesting the dosage effects of risk alleles on the age of onset of disease. Recognizing that only the early-onset cases might represent the true autoimmune T1D in Asian populations, we see that STAT4 alleles and haplotype might influence cytokine signaling and, therefore, development of T1D.

  7. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shuyuan [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Chen, Jiaxi [The University of Texas Southwestern Medical Center at Dallas, Medical School, 5235 Harry Hine Blvd., Dallas, TX (United States); Huang, Pintong [Department of Ultrasonography, The 2nd Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang Province (China); Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Grayburn, Paul A., E-mail: paulgr@baylorhealth.edu [Baylor Research Institute, Baylor University Medical Center, 3812 Elm Street, Dallas, TX (United States); Department of Internal Medicine, Division of Cardiology, Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall St, Suite H030, Dallas, TX (United States)

    2015-03-20

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.

  8. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    International Nuclear Information System (INIS)

    Chen, Shuyuan; Chen, Jiaxi; Huang, Pintong; Meng, Xing-Li; Clayton, Sandra; Shen, Jin-Song; Grayburn, Paul A.

    2015-01-01

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocation of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation

  9. A rare case of peripartum cardiomyopathy posted for caesarean section

    Directory of Open Access Journals (Sweden)

    Nalini Kotekar

    2007-01-01

    Full Text Available Post Partum Cardiomyopathy (PPCM is a relatively rare form of heart failure associated with pregnancy. It was recognized first in the 19th century by Ritchie and is defined as the onset of acute heart failure in the last trimester or early post partum period in the absence of infections, metabolic, toxic, ischaemic or valvular causes of myocardial dysfunction. Prognosis depends on the degree of cardiomegaly at presentation and in the following 6 months. Initial high risk period carries a mortality of 25 to 50%. Keeping in mind the reduced contractility and ejection fraction with ventricular dilatation proceeding to cardiac failure, the anesthesiologist managing a case of PPCM faces the challenge of avoiding myocardial depression, hypovolemia and increased SVR, all of which may be hazardous

  10. Peripartum Cardiomyopathy: Moving Towards a More Central Role of Genetics#

    Science.gov (United States)

    Cemin, Roberto; Janardhanan, Rajesh; Donazzan, Luca; Daves, Massimo

    2013-01-01

    Peripartum cardiomyopathy (PCM) is a relatively rare disease with potentially devasting consequences requiring prompt identification and correct treatment. Overall prognosis is good in majority of the cases, although some patients may progress to irreversible heart failure. Early diagnosis is important and effective treatment reduces mortality rates and increases the chance of complete recovery of ventricular systolic function. The aetiology and pathogenesis seems to be multifactorial and poorly understood, with the available literature rather conflicting. In recent years, there has been increased interest in the role played by genetic predisposition in the development of PCM. It probably develops as a result of a complex interaction of pregnancy-associated factors and genetic factors and recently there have been many observations pointing out the central role played by a genetic predisposition. The direct and indirect observations on genetic susceptibility may offer new insights into the pathogenesis of PCM. However, larger studies are needed before advising routine genetic testing in these patients. PMID:23909634

  11. Early Assessment of Cost-effectiveness of Gastric Electrical Stimulation for Diabetic Nausea and Vomiting

    DEFF Research Database (Denmark)

    Klinge, Mette Winther; Rask, Peter; Mortensen, Lene Sundahl

    2017-01-01

    stimulation (GES) may be offered in selected cases, as a minimally invasive, but expensive, therapeutic option. Our aims are to evaluate the clinical effect and the cost-utility of GES as a treatment for severe diabetic recurrent nausea and/or vomiting. Methods Among 33 diabetes patients implanted with GES...... to gastrointestinal dysfunction was calculated using hospital records 12 months prior to and 12 months after implantation. Results The surgical procedures were performed without mortality or major complications. Six months after surgery 78% of the respondents had at least 50% reduction in time with nausea and 48% had....../or vomiting. The procedure is supposed as cost-effective over a 2-year time horizon....

  12. The acidity of early pregnancy diet and risk of gestational diabetes mellitus.

    Science.gov (United States)

    Saraf-Bank, Sahar; Tehrani, Hotav; Haghighatdoost, Fahimeh; Moosavian, Seyedeh Parisa; Azadbakht, Leila

    2017-10-03

    Recently, an increasing interest has been addressed to the acid-base imbalance in the pathogenesis of diabetes while we are not aware of any study among patients affected by gestational diabetes mellitus (GDM). Therefore, the purpose of present study was to reveal the potential relation between dietary acid load (DAL) and glycemic indices, lipid profiles and GDM odds ratio among Iranian pregnant women with GDM. This case-control study (hospital-based setting) was performed in singleton fetus pregnant women; healthy (n = 263) and GDM (n = 200), aged 22-44 years, and between weeks 5-28 of pregnancy. Three-day 24-h dietary records were applied to determine usual intakes of women. The tertiles of protein to potassium ratio (Pr/K) and potential renal acid load (PRAL) were calculated and used for statistical analyses. Across tertiles of both DAL scores, fasting blood sugar, HbA1C, total cholesterol and LDL-C increased significantly. Diastolic blood pressure of participants significantly increased only across the tertiles of Pr/K ratio. Participants in the highest tertile of Pr/K and PRAL had more than 7 (OR = 7.60; 95% CI: 3.43-16.84) and 9 times (OR = 9.27; 95% CI: 4.00-21.46) increased odds of gestational diabetes mellitus, respectively. Women with higher scores of DAL were more likely to have gestational diabetes mellitus during pregnancy. Copyright © 2017. Published by Elsevier Ltd.

  13. Early central diabetes insipidus: An ominous sign in post-cardiac arrest patients.

    Science.gov (United States)

    Chae, Minjung Kathy; Lee, Jeong Hoon; Lee, Tae Rim; Yoon, Hee; Hwang, Sung Yeon; Cha, Won Chul; Shin, Tae Gun; Sim, Min Seob; Jo, Ik Joon; Song, Keun Jeong; Rhee, Joong Eui; Jeong, Yeon Kwon

    2016-04-01

    Central diabetes insipidus (CDI) after cardiac arrest is not well described. Thus, we aim to study the occurrences, outcomes, and risk factors of CDI of survivors after out-of-hospital cardiac arrest (OHCA). We retrospectively analyzed post-OHCA patients treated at a single center. Central diabetes insipidus was retrospectively defined by diagnostic criteria. One-month cerebral performance category (CPC) scores were collected for outcomes. Of the 169 patients evaluated, 36 patients (21.3%) were diagnosed with CDI. All CDI patients had a poor neurologic outcome of either CPC 4 (13.9%) or CPC 5 (86.1%), and CDI was strongly associated with mortality. Age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93-0.99), respiratory arrest (OR, 6.62; 95% CI, 1.23-35.44), asphyxia (OR, 9.26; 95% CI, 2.17-34.61), and gray to white matter ratio on brain computed tomogram (OR, 0.88; 95% CI, 0.81-0.95) were associated with the development of CDI. The onset of CDI was earlier (P diabetes insipidus patients with death or brain death had earlier occurrence of CDI and more maximum urine output. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Early changes in retinal structure and BMP2 expression in the retina and crystalline lens of streptozotocin-induced diabetic pigs.

    Science.gov (United States)

    Jeong, Jae Seung; Lee, Woon-Kyu; Moon, Yeon Sung; Kim, Na Rae

    2017-09-01

    This study aims to evaluate early changes in retinal structure and BMP2 expression in the retina and crystalline lens by comparing streptozotocin-induced diabetic pigs and normal control group pigs. Five eye samples from five diabetic Micro-pigs (Medikinetics, Pyeongtaek, Korea) and five eye samples from five control pigs bred in a specific pathogen-free area were used. Diabetes was developed through intravenous injection of nicotinamide and streptozotocin, and the average fasting glucose level was maintained at 250 mg/dL or higher for 16 weeks. To evaluate BMP2 expression in the retina and crystalline lens, Western blotting was performed. In Hematoxylin and Eosin staining, most diabetic pigs showed structural abnormalities in the inner plexiform layer. The number of nuclei in the ganglion cell layer within the range of 10 4 µm 2 was 3.78±0.60 for diabetic pigs and 5.57±1.07 for control group pigs, showing a statistically significant difference. In immunohistochemical staining, diabetic retinas showed an overall increase in BMP2 expression. In Western blotting, the average BMP2/actin level of diabetic retinas was 1.19±0.05, showing a significant increase compared to the 1.06±0.03 of the control group retinas ( P =0.016). The BMP2/actin level of diabetic crystalline lenses was similar to the control group crystalline lenses ( P =0.730). Compared to control group pigs, the number of nuclei in the inner nuclear layer of retinas from streptozotocin-induced diabetic pigs decreased, while an increase in BMP2 expression was observed in the retina of diabetic pigs.

  15. Small Molecule Inhibiting Nuclear Factor-kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan-Induced Diabetic Nephropathy in Rat.

    Science.gov (United States)

    Borgohain, Manash P; Lahkar, Mangala; Ahmed, Sahabuddin; Chowdhury, Liakat; Kumar, Saurabh; Pant, Rajat; Choubey, Abhinav

    2017-05-01

    Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. Nuclear factor kB (NF-kB)-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and NF-kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX). Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body-weight (b.w.) of ALX. Diabetic rats were treated with Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral treatment, PCTNL significantly restored blood sugar level, glomerular filtration rate, serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase and glutathione and the elevated levels of malondialdehyde and nitric oxide. Moreover, piceatannol-treated groups showed marked inhibition of renal pro-inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in terms of body-weight gain, PCTNL failed to effect significantly. However, overall findings clearly demonstrated that PCTNL provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF-kB activation - and might be helpful in early stage of diabetic nephropathy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  16. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

    Directory of Open Access Journals (Sweden)

    Poulton Joanna

    2009-04-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

  17. Serum ferritin concentration in early pregnancy and risk of subsequent development of gestational diabetes: A prospective study

    Directory of Open Access Journals (Sweden)

    Sedigheh Soheilykhah

    2017-08-01

    Full Text Available Background: Elevated serum ferritin concentration is associated with insulin resistance and diabetes. Recently it has also been described in gestational diabetes mellitus (GDM. Objective: A prospective study was done to determine whether there was a relationship between serum ferritin concentration in early pregnancy and the risk of GDM. Materials and Methods: A study was performed on 1,384 pregnant women with gestational age of 12-16 weeks. A blood sample was obtained for measurement of ferritin in the first trimester. Diagnosis of GDM was done by 75 gr oral glucose tolerance test between 24-28 wk. Results: Women who developed GDM had a higher concentration of serum ferritin than women who did not develop GDM (p=0.01. A ferritin concentration of 45 ng/ml was calculated to be the 75th percentile for healthy pregnant women. Considering this level 32% in the GDM group and 25.2%of normal subjects exhibited high ferritin levels (p=0.01. The risk of GDM with these high levels of ferritin was 1.4-fold higher than that for subjects with lower concentrations. The Odds Ratio was 1.4 (95% CI= 1-1.87 (p=0.01. After adjusted for age Odds Ratio was 1.38 (95% CI=1.02-1.86 (p=0.03 and after adjustment for pre-pregnancy Body Mass index, the adjusted odds ratio was 1.31 (CI= 0.96-1.79 (p=0.08. After multivariable adjustment (age and body mass index, the adjusted odds ratio was 1.3 (0.95-1.8 (p=0.09. Conclusion: High serum ferritin can be regarded as a significant risk factor for the development of gestational diabetes.

  18. Effect of chicory seed extract on glucose tolerance test (GTT and metabolic profile in early and late stage diabetic rats

    Directory of Open Access Journals (Sweden)

    Ghamarian Abdolreza

    2012-10-01

    Full Text Available Abstract Background and purpose of the study The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT and blood biochemical indices of experimentally-induced hyperglycemic rats. Methods Late stage and early stage of Type 2 diabetes mellitus (T2DM were induced in rats by streptozotocin (STZ and a combination of STZ and niacinamide (NIA/STZ, respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days. Body weight and fasting blood sugar (FBS were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c and sera for alanine aminotransferase (ALT, aspartate aminotransferase (AST, nitric oxide (NO, triacylglycerol (TG, total cholesterol (TC, total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days. Results During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p Conclusions Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned and long-term (28 days, in this study effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.

  19. Prevalence of early and late prematurity is similar among pediatric type 1 diabetes patients and the general population.

    Science.gov (United States)

    Adar, Adi; Shalitin, Shlomit; Eyal, Ori; Loewenthal, Neta; Pinhas-Hamiel, Orit; Levy, Milana; Dally-Gottfried, Orna; Landau, Zohar; Zung, Amnon; Levy-Khademi, Floris; Zangen, David; Tenenbaum-Rakover, Yardena; Rachmiel, Marianna

    2018-02-22

    The incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades, as has the incidence of preterm births (prematurity and early prematurity (prematurity and birth season were compared with the general population birth registry using Pearson Chi-square test. The study population included 1452 T1DM patients, 52.7% males, and 2 138 668 subjects in the general non-T1DM population, 51.2% males. The prevalence of late and early prematurity was similar between groups (6.1% and 2.2% in the T1DM group vs 5.6% and 2.0% in the general non-T1DM group, P = 0.25 and P = 0.38, respectively). OR for prematurity among T1DM patients was 1.15 (0.95-1.39), P = 0.16. No difference in birth season was demonstrated between preterm and term, in T1DM and general non-T1DM populations. Ethiopian descent was more prevalent among T1DM patients compared with the non-T1DM population, in both term and preterm born. This is the largest population-based study, and the first in the Middle East geographical area, indicating that prematurity, including early prematurity, is not associated with T1DM during childhood. The study was registered at https://clinicaltrials.gov/: NCT02929953. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Cushing's syndrome in pregnancy and neonatal hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Fayol, L; Masson, P; Millet, V; Simeoni, U

    2004-10-01

    Cushing's syndrome is rare in pregnancy but can cause spontaneous abortion, stillbirth or premature birth. We report a case of transient hypertrophic obstructive cardiomyopathy in a newborn whose mother had hypercortisolism due to a primary adrenal lesion. There was no family history of hypertrophic obstructive cardiomyopathy. Follow-up revealed complete resolution of the cardiac abnormalities in the infant. Cushing's syndrome in the mother resolved after delivery. Although maternal hypercortisolism seldom results in symptomatic hypercortisolism in the newborn, hypertrophic obstructive cardiomyopathy can occur.

  1. Early Detection of Atrophy of Foot Muscles in Chinese Patients of Type 2 Diabetes Mellitus by High-Frequency Ultrasonography

    Directory of Open Access Journals (Sweden)

    Xiaohui Wang

    2014-01-01

    Full Text Available The aim of this study was to evaluate the diagnostic value of high-frequency ultrasonography in detecting atrophy of foot muscles in Chinese patients of type 2 diabetes mellitus (T2DM. Chinese patients of T2DM with (n=56 or without (n=50 diabetic peripheral neuropathy (DPN and the control subjects (n=50 were enrolled. The nondominant foot of all subjects was examined with high-frequency ultrasonography. The transverse diameter, thickness, and cross-sectional area of the extensor digitorum brevis muscle (EDB and the thickness of the muscles of the first interstitium (MILs were measured. The results showed that the ultrasonographic transverse diameter, thickness, and cross-sectional area of EDB and the thickness of MILs in patients of T2DM with DPN were significantly smaller than those in patients of T2DM without DPN (all P<0.01 and those in the control subjects (all P<0.01. The transverse diameter and cross-sectional area of the EDB and thickness of MILs in patients of T2DM without DPN were significantly smaller than those of the control subjects (all P<0.01. In conclusion, the atrophy of foot muscle in Chinese T2DM patients can be detected by high-frequency ultrasonography. Notably, ultrasonography may detect early atrophy of foot muscles in patients without DPN.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  3. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pørksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule...... children. The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated...... for mutations of INS gene....

  4. Intrafamilial Variability of Early-Onset Diabetes due to an INS Mutation

    DEFF Research Database (Denmark)

    Fredheim, Siri; Svensson, Jannet; Pörksen, Sven

    2011-01-01

    Aim. The objective of this study was to describe the clinical characteristics of two siblings and their father carrying a C95Y mutation in the insulin (INS) gene. Methods/Results. A Danish patient, his sister, and his father were identified to carry the C95Y mutation in the preproinsulin molecule....... The father, insulin treated for over 40 years, has bilateral preproliferative retinopathy. Conclusions. These three cases further confirm the essential features of diabetes caused by INS mutations with proteotoxic effect. We conclude that patients with similar features must be investigated for mutations...

  5. Assessment of hypertrophic cardiomyopathy by ECG gated cardiac computed tomography

    International Nuclear Information System (INIS)

    Takeuchi, Kazuhide; Tanaka, Chujiro; Oku, Hisao

    1981-01-01

    The applicability of ECG gated cardiac computed tomography (CT) in 12 patients with hypertrophic cardiomyopathy was examined. Six of the 12 patients had hypertrophic obstructive cardiomyopathy, including one patient with mid-ventricular obstruction. Three of the 12 patients had hypertrophic non-obstructive cardiomyopathy, and three had apical hypertrophic cardiomyopathy. The diagnosis of hypertrophic cardiomyopathy was confirmed by the angiocardiogram in all patients. Cardiac CT was performed after intravenous administration of contrast media usually given as a bolus injection. The gantry was set with positive 20 0 tilt angle. In all patients with hypertrophic obstructive cardiomyopathy except for mid-ventricular obstruction, the hypertrophied interventricular septum in the basal and mid portions was observed, and the left ventricular cavity was narrowed in systole. In a patient with mid-ventricular obstruction, the marked hypertrophied interventricular septum and antero-lateral papillary muscle were observed. In diastole, the left ventricular cavity was narrow and divided into two parts. The apical cavity was completely disappeared in systole. In all patients with hypertrophic non-obstructive cardiomyopathy, the diffuse hypertrophied interventricular septum was observed in diastole. In systole, the apical portion of the left ventricular cavity was markedly narrow and antero-lateral papillary muscle was hypertrophic. In all patients with apical hypertrophic cardiomyopathy, the marked apical hypertrophy of the left ventricular wall was observed in diastole. It is concluded that ECG gated cardiac CT could estimate myocardial wall motion and thickness and differentiate the types of hypertrophic cardiomyopathy each other. (author)

  6. Body mass index in early and middle adult life: prospective associations with myocardial infarction, stroke and diabetes over a 30-year period: the British Regional Heart Study.

    Science.gov (United States)

    Owen, Christopher G; Kapetanakis, Venediktos V; Rudnicka, Alicja R; Wathern, Andrea K; Lennon, Lucy; Papacosta, Olia; Cook, Derek G; Wannamethee, S Goya; Whincup, Peter H

    2015-09-15

    Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks. A prospective cohort study. 7735 men with BMI measured in middle age (40-59 years) and BMI ascertained at 21 years from military records or participant recall. 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status. Among 4846 (63%) men (with complete data), a 1 kg/m(2) higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m(2) higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk. Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Serum uric acid concentration is associated with early changes of glomerular filtration rate in patients with diabetes type 1 without increased albumin excretion.

    Science.gov (United States)

    Spaleniak, Sebastian; Korzeniewska-Dyl, Irmina; Moczulski, Dariusz

    2014-10-01

    The early loss of renal function in patients with type 1 diabetes may begin before proteinuria. Only 30% of patients with diabetes manifest overt proteinuria. According to the previous studies, increased urinary albumin excretion, which is considered a classic marker of progression of diabetic kidney disease, can regress to normal urine albumin excretion. The current studies conducted in patients with type 1 diabetes without increased urine albumin excretion showed that the uric acid concentration was an independent factor for the development of diabetic kidney disease. The aim of study was to assess the impact of uric acid concentration and to identify risk factors of the early glomerular filtration loss in patients with type 1 diabetes and normal urinary albumin excretion. 147 patients (61 women and 86 men) with type 1 diabetes without increased urine albumin excretion were analysed. GFR (gromerular filtration rate) was estimated based on the serum cystatin C concentration. Centile charts were used to determine the variation of uric acid concentration depending on GFR and gender. The mean value of the filtration rate for the study group was 117 ml/min/m2. The uric acid level above 90th percentile in relation to GFR was diagnosed in 8.2% of women and 0% of men, between 90th and 50th percentile in 44.3 % of women and 5.8% of men and below 50th percentile in 47.5% of women and 94.2% of men. Contrary to men in women higher serum acid concentration was strongly associated with higher glomerular filtration rate. Hyperfiltraion was diagnosed in 15 of women and 19 of men. The high normal uric acid concentration in women with type 1 diabetes might play a crucial role in development of hyperfiltration.

  8. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    Science.gov (United States)

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Shiozaki, Afonso Akio; Parga, Jose Rodrigues; Arteaga, Edmundo; Rochitte, Carlos Eduardo; Tassi, Eduardo Marinho

    2007-01-01

    Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease that causes sudden death in young people, with an incidence of 1:500 adults. The routinely used criteria for worst prognosis have limited sensitivity and specificity. Thus, the estimated risk of evolving to dilated cardiomyopathy or sudden death is somewhat inaccurate, leading to management uncertainty of HCM patients. Therefore, an accurate noninvasive method for the diagnosis of HCM with prognostic value is of great importance. In the last years, Cardiovascular Magnetic Resonance (CMR) emerged not only as a diagnostic tool, but also as a study with prognostic values, by characterizing myocardial fibrosis with great accuracy in HCM patients. Additionally, CMR identifies the types of hypertrophy, analyses the ventricular function, estimates the intraventricular gradient and allows the determination of differential diagnosis. Moreover, CMR can uniquely access myocardial fibrosis in HCM. (author)

  10. Magnetic resonance imaging in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Ichida, Fukiko; Hamamichi, Yuuji; Hashimoto, Ikuo; Tsubata, Shinichi; Miyazaki, Ayumi; Okada, Toshio; Futatsuya, Ryuusuke; Okada, Eikichi

    1994-01-01

    To evaluate the capability of magnetic resonance imaging (MRI) in the anatomical diagnosis and tissue characterization, 8 children with hypertrophic cardiomyopathy were studied comparing with echocardiography and 201 Tl myocardial imaging. The severity and distribution of hypertrophy were comparable on echocardiography and MRI. MRI was superior to echocardiography to demonstrate the apical hypertrophy. In 4 patients with severe hypertrophy, heterogenous high signal intensity was demonstrated in the site of hypertrophy, which was enhanced by T 2 weighted imaging. In the patient with decreased cardiac performance and progressed cardiac failure, the heterogeneity and high signal intensity progressed in one year interval. Simultaneously performed 201 Tl myocardial imaging showed patchy perfusion defect. Histological findings of the left ventricle demonstrated hypertrophy, degeneration and marked dysarray of the myocytes and fibrosis. MRI has the potential ability for the evaluation and sequential monitoring of myocardial tissue characterization as well as cardiac anatomy in childhood hypertrophic cardiomyopathy. (author)

  11. Magnetic resonance imaging in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ichida, Fukiko; Hamamichi, Yuuji; Hashimoto, Ikuo; Tsubata, Shinichi; Miyazaki, Ayumi; Okada, Toshio; Futatsuya, Ryuusuke; Okada, Eikichi [Toyama Medical and Pharmaceutical Univ. (Japan)

    1994-02-01

    To evaluate the capability of magnetic resonance imaging (MRI) in the anatomical diagnosis and tissue characterization, 8 children with hypertrophic cardiomyopathy were studied comparing with echocardiography and [sup 201]Tl myocardial imaging. The severity and distribution of hypertrophy were comparable on echocardiography and MRI. MRI was superior to echocardiography to demonstrate the apical hypertrophy. In 4 patients with severe hypertrophy, heterogenous high signal intensity was demonstrated in the site of hypertrophy, which was enhanced by T[sub 2] weighted imaging. In the patient with decreased cardiac performance and progressed cardiac failure, the heterogeneity and high signal intensity progressed in one year interval. Simultaneously performed [sup 201]Tl myocardial imaging showed patchy perfusion defect. Histological findings of the left ventricle demonstrated hypertrophy, degeneration and marked dysarray of the myocytes and fibrosis. MRI has the potential ability for the evaluation and sequential monitoring of myocardial tissue characterization as well as cardiac anatomy in childhood hypertrophic cardiomyopathy. (author).

  12. Retinal Vascular Fractals Correlate With Early Neurodegeneration in Patients With Type 2 Diabetes Mellitus

    DEFF Research Database (Denmark)

    Frydkjaer-Olsen, Ulrik; Soegaard Hansen, Rasmus; Pedersen, Knud

    2015-01-01

    . In a randomly selected eye of each patient, Fd was calculated using SIVA-Fractal, a specialized semiautomatic software. Retinal neurodegeneration was evaluated by Topcon 3D OCT-2000 spectral-domain optical coherence tomography (OCT) and by a RETI-scan multifocal ERG (mf-ERG) system in rings one to six. Level...... were 10 (42.7%), 20 (35.0%), and 35 (22.3%), respectively. Fd correlated inversely with mf-ERG implicit time of ring one (r = -0.25, P = 0.01) and present diabetic neuropathy (P = 0.02), and positively with OCT ganglion cell layer (GCL) thickness (r = 0.20, P = 0.04). In a multivariable linear...... regression model, Fd was associated with mf-ERG implicit time of ring one (coefficient -0.0021/ms, P = 0.040) and the presence of diabetic neuropathy (coefficient -0.0209 for neuropathy present versus absent, P = 0.041). Conclusions: In patients with T2DM and no or minimal DR, independent correlations were...

  13. Activin a is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes

    NARCIS (Netherlands)

    Chen, Weena J. Y.; Greulich, Sabrina; van der Meer, Rutger W.; Rijzewijk, Luuk J.; Lamb, Hildo J.; de Roos, Albert; Smit, Johannes W. A.; Romijn, Johannes A.; Ruige, Johannes B.; Lammertsma, Adriaan A.; Lubberink, Mark; Diamant, Michaela; Ouwens, D. Margriet

    2013-01-01

    Activin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic

  14. Apical ballooning with mid-ventricular obstruction: the many faces of Takotsubo cardiomyopathy

    Science.gov (United States)

    Spadotto, Veronica; Elmaghawry, Mohamed; Zorzi, Alessandro; Migliore, Federico; Marra, Martina Perazzolo

    2013-01-01

    Takotsubo cardiomyopathy (TTC) is a transient left ventricular dysfunction due to akinesia of the left-ventricular (LV) mid-apical segments (apical ballooning), which can cause severe reduction in LV systolic function. The typical clinical picture of TTC include chest pain, electrocardiographic changes consisting of mild ST-segment elevation followed by diffuse deep T-wave inversion, QTc interval prolongation and mild troponin release in the absence of significant coronary stenoses. The syndrome often affects post-menopausal women and is triggered by sympathetic overstimulation, like intense physical or emotional stress, so that it is called the “broken heart syndrome”. Although left-ventricular systolic dysfunction usually fully recovers within few days, heart failure can still complicate the early phase. We report a case of stress-induced cardiomyopathy that had full recovery after 4 weeks of follow up. The main electrocardiographic, angiographic and imaging features are discussed. PMID:24689016

  15. Magnetic resonance imaging of dilated cardiomyopathy; MRT bei dilatativen Kardiomyopathien

    Energy Technology Data Exchange (ETDEWEB)

    D' Anastasi, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Greif, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Medizinische Klinik und Poliklinik I, Muenchen (Germany); Reiser, M.F.; Theisen, D. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Deutsches Zentrum fuer Herzkreislaufforschung (DZHK), Muenchen (Germany)

    2013-01-15

    Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy with a prevalence of 1 out of 2,500 in adults. Due to mild clinical symptoms in the early phase of the disease, the true prevalence is probably even much higher. Patients present with variable clinical symptoms ranging from mild systolic impairment of left ventricular function to congestive heart failure. Even sudden cardiac death may be the first clinical symptom of DCM. The severity of the disease is defined by the degree of impairment of global left ventricular function. Arrhythmias, such as ventricular or supraventricular tachycardia, atrioventricular (AV) block, ventricular extrasystole and atrial fibrillation are common cardiac manifestations of DCM. Magnetic resonance imaging (MRI) plays an important role in the exact quantification of functional impairment of both ventricles and in the evaluation of regional wall motion abnormalities. With its excellent ability for the assessment of myocardial structure, it is becoming increasingly more important for risk stratification and therapy guidance. (orig.) [German] Die dilatative Kardiomyopathie (DCM) ist die haeufigste Form der Kardiomyopathie mit einer Praevalenz von 1/2500 Erwachsenen. Aufgrund der zunaechst milden klinischen Symptomatik ist jedoch von einer relativ hohen Dunkelziffer auszugehen. Die klinische Praesentation ist variabel, die Schwere der Erkrankung wird vom Ausmass der systolischen Funktionseinschraenkung bestimmt. Herzrhythmusstoerungen, wie ventrikulaere oder supraventrikulaere Tachykardien, AV-Blockierungen, ventrikulaere Extrasystolen und Vorhofflimmern sind moegliche klinische Manifestationen. Bei manchen Patienten ist der ploetzliche Herztod die erste klinische Manifestation der Erkrankung. Die kardiale MRT spielt eine bedeutende Rolle fuer die Beurteilung des Ausmasses der ventrikulaeren Dilatation, Dysfunktion und fuer die Beurteilung regionaler Wandbewegungsstoerungen. Darueber hinaus kann sie zur Anwendung kommen

  16. Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy in TYpe 2 diabetic patients with normoalbuminuria (PRIORITY)

    DEFF Research Database (Denmark)

    Lindhardt, Morten; Persson, Frederik; Currie, Gemma

    2016-01-01

    INTRODUCTION: Diabetes mellitus affects 9% of the European population and accounts for 15% of healthcare expenditure, in particular, due to excess costs related to complications. Clinical trials aiming for earlier prevention of diabetic nephropathy by renin angiotensin system blocking treatment...... AND DISSEMINATION: The study will be conducted under International Conference on Harmonisation - Good clinical practice (ICH-GCP) requirements, ethical principles of Declaration of Helsinki and national laws. This first new biomarker-directed intervention trial aiming at primary prevention of diabetic nephropathy...

  17. Screening for Microalbuminuria in the early detection of diabetic nephropathy: A cheap and simple method

    Directory of Open Access Journals (Sweden)

    "Larijani B

    2002-06-01

    Full Text Available Prompt detection of renal involvement through evaluation of microalbuminuria can both reduce mortality in diabetic patients and significantly reduce the cost of managing these patients. To this end, Micral test strips have been used as a screeing tool in this group of patients though not yet in our country. The present study aimed to evaluate this test and to abtain a simpler and less expensive method of screening for microlbuminuria. In this study, 200 type 1 and type 2 diabetic patients referred to the Endocrine & Metabolims Research Center of the Tehran university of medical Sciences were evaluated for microabluminuria. Entry criteria consisted of a history of recognized diabetes longer than or equal to 5 years. Exclusion criteria included development of urinary tract infection, pyrexia, and a history of uncontrolled hypertension. Every patient first completed a data questionnaire and then provided a first-void urine sample, which was tested for microalbuminuria with a urinary protein test strip (an Iranian-made Uri-Yab and a German-made BM-test-GP strip and the sulphasalicylic acid chemical method. Negative samples were tested further using Micral test strips (based on gold-lable immunochromatograpy and the microalbumin measurement kit manufactured by Dako. Germany (based on turbidometry using a Hitachi autoanalyser. 126 women and 74 men were recruited into the study. The average age of the sample was 40.7 years (range=16 to 63 years; 17 patients had IDDM and 173, NIDDM. Average duration of recognized diabetes was 8.75 years. Based on results obtained using chemical analysis and foreign-made tests strips, 46 patients (23% had macroalbuminuria, though the detection rate using Iranian-made test strips was 18 percent (36 patients. A further 16.2 percent of patients had microalbuminuria, with an average urinary albumin excertion of 28.7 mg per liter. Compared with colorimetric methos, the Micral test yieled a sensitivity of 93% and a specificity

  18. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

    Science.gov (United States)

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H.; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-01-01

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2. PMID:28233855

  19. Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Chun Zhao

    Full Text Available BACKGROUND: Gestational diabetes mellitus (GDM is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM. METHODOLOGY/PRINCIPAL FINDINGS: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222 were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222 were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1 expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2 in HepG2 cell lines. CONCLUSIONS/SIGNIFICANCE: Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.

  20. Early retirement and the influence on healthcare budgets and insurance premiums in a diabetes population.

    Science.gov (United States)

    Walzer, Stefan

    2007-01-01

    To contribute to current discussions about budget impact modeling, two different approaches for the impact of a new pharmaceutical product were analyzed: firstly considering the impact on annual healthcare expenditures only, and secondly additional inclusion of lost insurance premiums due to possible early retirement in patients with chronic diseases. The dynamic model calculates the budget impact from two different perspectives: (a) the impact on healthcare expenditures and (b) on expenditures as well as on health insurance revenues due to premiums. The latter approach could especially be useful for patients with chronic diseases who have higher probabilities of early retirement. Early retirement rates and indirect costs were derived from published data. Healthcare premiums were calculated based on an average premium and a mean income. Epidemiological input data were obtained from the literature. Time horizon was 10 years. Results in terms of reimbursement decisions of the budget impact analysis varied depending on the assumptions made for the insurance premiums, costs, and early retirement rate. Sensitivity analyses revealed that in extreme cases the decision for accepting a new pharmaceutical product would probably be negative using approach (a), but positive using approach (b). Depending on the disease and population of interest in a budget impact analysis, not only the healthcare expenditures for a health insurance have to be considered but also the revenue side for an insurance due to retirement should be included.

  1. Early Onset of Type 1 Diabetes and Educational Field at Upper Secondary and University Level: Is Own Experience an Asset for a Health Care Career?

    Science.gov (United States)

    Steen Carlsson, Katarina

    2017-01-01

    Ill health in early life has a significant negative impact on school grades, grade repetition, educational level, and labor market outcomes. However, less is known about qualitative socio-economic consequences of a health shock in childhood or adolescence. We investigate the relationship between onset of type 1 diabetes up to age 15 and the probability of choosing and completing a health-oriented path at upper secondary and university level of education. We analyze the Swedish Childhood Diabetes Register, the National Educational Register, and other population registers in Sweden for 2756 people with type 1 diabetes and 10,020 matched population controls. Educational decisions are modeled as unsorted series of binary choices to assess the choice of educational field as a potential mechanism linking early life health to adult outcomes. The analyses reject the hypothesis of no systematic differences in choice of educational field between people with and without type 1 diabetes at both levels. The results are robust to selection on ability proxies and across sensitivity analysis. We conclude that the observed pro health-oriented educational choices among people with type 1 diabetes in our data are consistent with disease onset in childhood and adolescence having qualitative impact on life-course choices. PMID:28665347

  2. Early Onset of Type 1 Diabetes and Educational Field at Upper Secondary and University Level: Is Own Experience an Asset for a Health Care Career?

    Science.gov (United States)

    Lovén, Ida; Steen Carlsson, Katarina

    2017-06-30

    Ill health in early life has a significant negative impact on school grades, grade repetition, educational level, and labor market outcomes. However, less is known about qualitative socio-economic consequences of a health shock in childhood or adolescence. We investigate the relationship between onset of type 1 diabetes up to age 15 and the probability of choosing and completing a health-oriented path at upper secondary and university level of education. We analyze the Swedish Childhood Diabetes Register, the National Educational Register, and other population registers in Sweden for 2756 people with type 1 diabetes and 10,020 matched population controls. Educational decisions are modeled as unsorted series of binary choices to assess the choice of educational field as a potential mechanism linking early life health to adult outcomes. The analyses reject the hypothesis of no systematic differences in choice of educational field between people with and without type 1 diabetes at both levels. The results are robust to selection on ability proxies and across sensitivity analysis. We conclude that the observed pro health-oriented educational choices among people with type 1 diabetes in our data are consistent with disease onset in childhood and adolescence having qualitative impact on life-course choices.

  3. Lifestyle patterns in early pregnancy linked to gestational diabetes mellitus diagnoses when using IADPSG criteria. The St Carlos gestational study.

    Science.gov (United States)

    Ruiz-Gracia, Teresa; Duran, Alejandra; Fuentes, Manuel; Rubio, Miguel A; Runkle, Isabelle; Carrera, Evelyn F; Torrejón, María J; Bordiú, Elena; Valle, Laura Del; García de la Torre, Nuria; Bedia, Ana R; Montañez, Carmen; Familiar, Cristina; Calle-Pascual, Alfonso L

    2016-06-01

    Early-pregnancy lifestyle (EPL) could influence the development of gestational diabetes mellitus(GDM), depending on the diagnostic criteria used. We studied EPL in 1750 pregnant women using Carpenter-Coustan criteria(CCc), and in 1526 with the International Association of Diabetes and Pregnancy Study Groups criteria(IADPSGc). GDM risk factors were assessed in women between 24 and 28 weeks of gestational age during two consecutive years. A semiquantitative frequent-food-consumption questionnaire was used to evaluate lifestyle during pregnancy. Multiple logistic regression analysis was conducted to assess GDM risk with different lifestyle patterns. Using IADPSGc, the GDM ORs (95%CI) for intake/week were: nuts >3 times: 0.59 (0.39-0.91; p < 0.015), refined cereals ≤1 serving: 0.72(0.58-0.89; p < 0.003), juices <4 servings: 0.77 (0.62-0.95; p < 0.017), cookies and pastries <4 servings: 0.71(0.57-0.89; p < 0.003) as compared to opposite habits. No significant nutritional patterns were found to be significant using CCc. The OR (95%CI) for GDM with none of the four risk patterns as compared to having three-four risk factors was 0.21(0.07-0.62; p < 0.005), remaining significant after stratification by BMI, age, obstetric events, parity and family history. The multiple logistic regression model including nutritional categories and pregestational BMI, age, obstetric history, parity, personal/family history, had an area under the curve(AUC) of the receiver operating curve(ROC) for the probability to predict GDM of 0.66 (CI 95%: 0.63-0.69; p < 0.001). Our study is the first to identify four early-pregnancy nutritional patterns associated with the GDM when using IADPSGc. Adherence to a low-risk nutritional pattern from early pregnancy on could be an effective strategy for GDM prevention. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  4. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

    Science.gov (United States)

    Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P; Lang, Gabriele E; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, Rafael

    2017-09-01

    This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes. © 2017 by the American Diabetes Association.

  5. Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

    Science.gov (United States)

    Tanamas, Stephanie K; Reddy, Sanil P; Chambers, Melissa A; Clark, Elena J; Dunnigan, Diana L; Hanson, Robert L; Nelson, Robert G; Knowler, William C; Sinha, Madhumita

    2017-12-28

    The risk of early-onset type 2 diabetes associated with the severity of obesity in youth is not well understood. This study aims to determine metabolic alterations and type 2 diabetes risk among American Indian children who are obese or severely obese. Incidence rates of diabetes before 20 years (youth-onset) and 45 years were computed in 2728 children who were from 5 to Obesity was defined as age-sex-adjusted body mass index (BMI) ≥95th percentile, and its severity was quantified as the percentage of the 95th percentile (%BMI p95 ). In the younger cohort, 0.9% of those non-obese and 2.9% of those with 100% to obese and 9.8% of those with 100% to youth-onset diabetes was 3.8 and 4.9/1000 person-years in the child and adolescent cohorts, respectively, and before the age of 45 was 12.3 and 16.8/1000 person-years, respectively. Incidence rates of youth-onset diabetes in those with the most severe obesity (≥140%BMI p95 ) were 2.3 to 5.1 times as high as in those with the least severe obesity (100 to obesity in an American Indian population is a major driver of type 2 diabetes developing in adolescents and young adults. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  6. Risk factors and direct medical cost of early versus late unplanned readmissions among diabetes patients at a tertiary hospital in Singapore.

    Science.gov (United States)

    Png, May Ee; Yoong, Joanne; Chen, Cynthia; Tan, Chuen Seng; Tai, E Shyong; Khoo, Eric Y H; Wee, Hwee Lin

    2018-02-20

    To examine the risk factors and direct medical costs associated with early (≤30 days) versus late (31-180 days) unplanned readmissions among patients with type 2 diabetes in Singapore. Risk factors and associated costs among diabetes patients were investigated using electronic medical records from a local tertiary care hospital from 2010 to 2012. Multivariable logistic regression was used to identify risk factors associated with early and late unplanned readmissions while a generalized linear model was used to estimate the direct medical cost. Sensitivity analysis was also performed. A total of 1729 diabetes patients had unplanned readmissions within 180 days of an index discharge. Length of index stay (a marker of acute illness burden) was one of the risk factors associated with early unplanned readmission while patient behavior-related factors, like diabetes-related medication adherence, were associated with late unplanned readmission. Adjusted mean cost of index admission was higher among patients with unplanned readmission. Sensitivity analysis yielded similar results. Existing routinely captured data can be used to develop prediction models that flag high risk patients during their index admission, potentially helping to support clinical decisions and prevent such readmissions.

  7. Takotsubo cardiomyopathy in a snake bite victim: a case report ...

    African Journals Online (AJOL)

    Takotsubo cardiomyopathy occurs in patients with severe emotional or physiologic stress. The prognosis is usually favorable, and the left ventricular wall motion dyskinesis normalizes within days to weeks. In this paper we report a case of snake bite complicated by takotsubo cardiomyopathy. We advise physicians to ...

  8. Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy. Cross-sectional Analyses of Baseline Data of the EUROCONDOR project

    DEFF Research Database (Denmark)

    Santos, Ana Rita; Ribeiro, Luisa; Bandello, Francesco

    2017-01-01

    Cross-sectional study evaluating the relationship between: a) functional and structural measurements of neurodegeneration in initial stages of diabetic retinopathy (DR); and b) presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of patients with type 2...... diabetes (n=449) enrolled in the EUROCONDOR study (NCT01726075). Functional studies by multifocal ERG (mfERG) evaluated neurodysfunction and structural measurements using spectral domain optical-coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1...

  9. Short-term inhibition of prostaglandin synthesis has no effect on the elevated glomerular filtration rate of early insulin-dependent diabetes

    DEFF Research Database (Denmark)

    Christiansen, J S; Feldt-Rasmussen, B; Parving, H H

    1985-01-01

    Glomerular filtration rate and renal plasma flow (constant infusion technique using 125I-iothalamate and 131I-hippuran) were measured twice within a 1-week interval in nine young males with insulin-dependent diabetes of short duration (2-5 years). The study was performed in a randomized double...... +/- 43 versus 560 +/- 52 ml/min X 1.73 m2), when measured during placebo or indomethacin treatment, respectively. It is concluded that the steady-state enhancement of glomerular filtration rate and renal plasma flow found in early insulin-dependent diabetes is not due to an excessive activity...

  10. Associations between gestational diabetes mellitus and elevated HbA1c early postpartum in a multi-ethnic population.

    Science.gov (United States)

    Waage, Christin; Jenum, Anne Karen; Mdala, Ibrahimu; Berg, Jens Petter; Richardsen, Kåre; Birkeland, Kåre

    2017-04-01

    To investigate the prevalence of elevated HbA 1c 14 weeks postpartum in different ethnic groups and in women with and without gestational diabetes mellitus (GDM) in the index pregnancy and to explore demographic and biological factors from early pregnancy associated with elevated HbA 1c (HbA 1c ≥5.7% (≥39mmol/mol)) postpartum. From a cohort study in Oslo, Norway, we included 570 pregnant women, examined in gestational week 15, 28, and 14 weeks postpartum. The association between elevated HbA 1c and demographic and biological factors were assessed by logistic regression analyses. The prevalence of elevated HbA 1c postpartum was 23% in the total population, 15% among Western Europeans and 28% among women with ethnic minority background (p<0.01). In ethnic minorities elevated HbA 1c was found in 39% of women with recent GDM diagnosed by the World Health Organization 2013 criteria and in 21% of women without GDM (p<0.01), compared to 22% and 13% in Western Europeans (p=0.11). We found independent associations between elevated HbA 1c and ethnic minority background (OR 2.0, 95% CI 1.27, 3.18), and GDM (OR 2.04, 95% CI 1.35, 3.10) (p<0.01). The prevalence of elevated HbA 1c postpartum was 23%, and significantly higher among women with ethnic minority background irrespective of GDM. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  11. Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth.

    Science.gov (United States)

    Vehik, Kendra; Cuthbertson, David; Boulware, David; Beam, Craig A; Rodriguez, Henry; Legault, Laurent; Hyytinen, Mila; Rewers, Marian J; Schatz, Desmond A; Krischer, Jeffrey P

    2012-09-01

    The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects TrialNet Natural History (TrialNet) studies and had an HbA(1c) within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140-199 mg/dL defined IGT, and an OGTT with 2-hPG ≥200 mg/dL or fasting plasma glucose ≥126 mg/dL defined diabetes. HbA(1c) ≥5.7% defined IGT, and HbA(1c) ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA(1c) compared with OGTT. There were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA(1c) sensitivity was very low across the studies (8-42%), and specificity was variable (64-95%). With HbA(1c) ≥6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA(1c) ≥6.5% for the development of T1D was variable (50-94%) across the four studies. HbA(1c) ≥6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA(1c) threshold is recommended if used as an alternative criterion in diagnosing T1D.

  12. An improved early detection method of type-2 diabetes mellitus using multiple classifier system

    KAUST Repository

    Zhu, Jia

    2015-01-01

    The specific causes of complex diseases such as Type-2 Diabetes Mellitus (T2DM) have not yet been identified. Nevertheless, many medical science researchers believe that complex diseases are caused by a combination of genetic, environmental, and lifestyle factors. Detection of such diseases becomes an issue because it is not free from false presumptions and is accompanied by unpredictable effects. Given the greatly increased amount of data gathered in medical databases, data mining has been used widely in recent years to detect and improve the diagnosis of complex diseases. However, past research showed that no single classifier can be considered optimal for all problems. Therefore, in this paper, we focus on employing multiple classifier systems to improve the accuracy of detection for complex diseases, such as T2DM. We proposed a dynamic weighted voting scheme called multiple factors weighted combination for classifiers\\' decision combination. This method considers not only the local and global accuracy but also the diversity among classifiers and localized generalization error of each classifier. We evaluated our method on two real T2DM data sets and other medical data sets. The favorable results indicated that our proposed method significantly outperforms individual classifiers and other fusion methods.

  13. Cushing’s Disease Presented by Reversible Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Berna İmge Aydoğan

    2015-01-01

    Full Text Available Introduction. Dilated cardiomyopathy is rarely reported among CS patients especially without hypertension and left ventricular hypertrophy. Materials and Methods. We hereby report a Cushing’s syndrome case presenting with dilated cardiomyopathy. Results. A 48-year-old female patient was admitted to our clinic with severe proximal myopathy and dilated cardiomyopathy without ventricular hypertrophy. Cushing’s disease was diagnosed and magnetic-resonance imaging of the pituitary gland revealed a microadenoma. Under diuretic and ketoconazole treatments, she underwent a successful transnasal/transsphenoidal adenomectomy procedure. Full recovery of symptoms and echocardiographic features was achieved after six months of surgery. Conclusion. Cushing’s syndrome must be kept in mind as a reversible cause of dilated cardiomyopathy. Recovery of cardiomyopathy is achieved with successful surgery.

  14. Radiology and pathology correlation in common infiltrative cardiomyopathies

    International Nuclear Information System (INIS)

    Varzeshi, Neda; Hansen, Mark; Rezaee, Amir; Slaughter, Richard; Dixon, Natalie; Duhig, Edwina

    2012-01-01

    Infiltrative cardiomyopathies generally pose a diagnostic dilemma as current diagnostic tools are imprecise. Invasive endomyocardial biopsy is considered as the gold standard however it has some limitations. Recently cardiovascular magnetic resonance (CMR) is emerging as an excellent technique in diagnosing infiltrative cardiomyopathies and is increasingly being used. Characteristic pathologic and radiologic findings in most common infiltrative cardiomyopathies (amyloid, sarcoid and Fabry's) are discussed and correlated with relative CMR and histologic examples. There is fairly good correlation between the non-invasive radiologic and the invasive histologic findings in common infiltrative cardiomyopathies. Non-invasive CMR with its high sensitivity and specificity has an excellent role in establishing the diagnosis and improving the prognosis of common infiltrative cardiomyopathies.

  15. Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood

    DEFF Research Database (Denmark)

    Samuelsson, Ulf; Anderzén, Johan; Gudbjörnsdottir, Soffia

    2016-01-01

    AIMS: To compare metabolic control between males and females with type 1 diabetes during adolescence and as young adults, and relate it to microvascular complications. METHODS: Data concerning 4000 adolescents with type 1 diabetes registered in the Swedish paediatric diabetes quality registry, an...

  16. Takotsubo Cardiomyopathy Associated with Thyrotoxicosis: A Case Report and Review of the Literature

    OpenAIRE

    Eliades, Myrto; El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D.

    2014-01-01

    Background: Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease.

  17. Influence of diabetes mellitus on heart failure risk and outcome

    Directory of Open Access Journals (Sweden)

    Van Belle Eric

    2003-01-01

    Full Text Available Abstract Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. The studies linking diabetes mellitus (DM with heart failure (HF The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. Treatment of heart failure in diabetic patients The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

  18. Basal wall hypercontraction of Takotsubo cardiomyopathy in a patient who had been diagnosed with dilated cardiomyopathy: a case report.

    Science.gov (United States)

    Ichihara, Noboru; Fujita, Shuichi; Kanzaki, Yumiko; Fujisaka, Tomohiro; Ozeki, Michishige; Ishizaka, Nobukazu

    2017-12-12

    Takotsubo cardiomyopathy is characterized by the basal hypercontractility and apical ballooning of the left ventriculum and T-wave inversion in the electrocardiogram. It has been suggested that Takotsubo cardiomyopathy might underlie the pathogenesis of persistent cardiac dysfunction; however, few reports are present demonstrating the advent of Takotsubo cardiomyopathy in patients with idiopathic cardiomyopathy. A 64-year-old women was admitted due to dyspnea on effort and lower extremity edema. She had been diagnosed with idiopathic dilated cardiomyopathy 2.5 years before owing to the reduced left ventricular ejection fraction (24%), normal coronary artery, and interstitial fibrosis of the myocardial samples. On admission, her electrocardiogram showed giant negative T wave in II, III, aVF, and precordial leads. Echocardiography showed dyskinesis of the left ventricular apex and hypercontraction of the basal wall, which had not been observed in the previous examinations. Coronary angiography showed normal coronary arteries, and apical ballooning and basal hypercontractility was confirmed by left ventriculography. On day 15 of admission, contraction of apical wall was recovered, and basal hypercontraction was disappeared. The present case is the first report demonstrating appearance the transient basal wall hypercontraction along with the advent of Takotsubo cardiomyopathy in a patient diagnosed with dilated cardiomyopathy. Whether such findings are indicative of fair prognosis and have the utility of understanding the pathogenesis of dilated cardiomyopathy needs further investigation.

  19. Deferiprone attenuates inflammation and myocardial fibrosis in diabetic cardiomyopathy rats

    International Nuclear Information System (INIS)

    Zou, Chunbo; Liu, Xiaogang; Xie, Rujuan; Bao, Yushi; Jin, Qing; Jia, Xibei; Li, Li; Liu, Ruichan

    2017-01-01

    We attempted to investigate the therapeutic effects of deferiprone on DC rats and explore the underlying mechanism. Total 24 6-week-old male Wistar rats (weighing from 180 g to 220 g) were subjected to DC model construction and then randomly divided to three groups (8 rats per group): DC group, DC + 50 mg, and DC + 100 mg deferiprone treatment group. The 8 normal rats were considered as controls. After deferiprone treatment for 20 weeks, the blood samples were collected for the biochemical parameters test, including fasting glucose, HOMA-IR (homeostasis model assessment of the insulin resistance), serum iron, ferritin and transferrin saturation (TS). The oxidative stress was assessed by detecting the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Histopathologic changes were determined by Masson's trichrome staining and electron microscopy imaging. The expression levels of NF-κB (nuclear factor kappa B), COX2 (cytochrome c oxidase), tenascin C, collagen IV were measured by RT-PCR and western blotting. The expression of nitrotyrosine and MCP-1 (monocyte chemotactic protein 1) were determined by immunohistochemistry. Deferiprone treatment reduced iron deposition and IR in DC rats except for blood glucose. After deferiprone treatment, MDA level was significantly decreased and SOD level was increased significantly. The level of NF-κB, cyclooxygenase-2, tenascin C, collagen IV MCP-1 and nitrotyrosine were significantly reduced. There was no significant difference in the effect of deferiprone at 50 and 100 mg doses. Deferiprone showed therapeutic effects on DC by regulating the pro-inflammatory and pro-fibrotic factors. - Highlights: • The expression of serum iron, ferritin and TS were elevated in DC rats. • Oxidative stress related MDA and SOD were upregulated in DC rats. • NF-κB, COX2, tenascin C, collagen IV were accumulated in DC rats. • All the changes were reversed by deferiprone treatment.

  20. Stress Induced Cardiomyopathy Triggered by Acute Myocardial Infarction: A Case Series Challenging the Mayo Clinic Definition.

    Science.gov (United States)

    Christodoulidis, Georgios; Kundoor, Vishwa; Kaluski, Edo

    2017-08-28

    BACKGROUND Various physical and emotional factors have been previously described as triggers for stress induced cardiomyopathy. However, acute myocardial infarction as a trigger has never been reported. CASE REPORT We describe four patients who presented with an acute myocardial infarction, in whom the initial echocardiography revealed wall motion abnormalities extending beyond the coronary distribution of the infarct artery. Of the four patients identified, the mean age was 59 years; three patients were women and two patients had underlying psychiatric history. Electrocardiogram revealed ST elevation in the anterior leads in three patients; QTc was prolonged in all cases. All patients had ≤ moderately elevated troponin. Single culprit lesion was found uniformly in the proximal or mid left anterior descending artery. Initial echocardiography revealed severely reduced ejection fraction with relative sparing of the basal segments, whereas early repeat echocardiography revealed significant improvement in the left ventricular function in all patients. CONCLUSIONS This is the first case series demonstrating that acute myocardial infarction can trigger stress induced cardiomyopathy. Extensive reversible wall motion abnormalities, beyond the ones expected from angiography, accompanied by modest elevation in troponin and marked QTc prolongation, suggest superimposed stress induced cardiomyopathy.

  1. Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.

    Directory of Open Access Journals (Sweden)

    Rocio Toro

    Full Text Available Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations.Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64 in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased, 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment.We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.

  2. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...... asymmetrical, and had similar late gadolinium enhancement patterns. Ischemic stroke and severe white matter lesions were more frequent among family A men, but neither family A nor family B men had overt renal disease. Family A and family B heterozygotes had less severe or no clinical manifestations...

  3. Genetics of Human and Canine Dilated Cardiomyopathy

    OpenAIRE

    Siobhan Simpson; Jennifer Edwards; Thomas F. N. Ferguson-Mignan; Malcolm Cobb; Nigel P. Mongan; Catrin S. Rutland

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In th...

  4. Genetic basis of early-onset, MODY-like diabetes in Japan and features of patients without mutations in the major MODY genes: dominance of maternal inheritance.

    Science.gov (United States)

    Yorifuji, Tohru; Higuchi, Shinji; Kawakita, Rie; Hosokawa, Yuki; Aoyama, Takane; Murakami, Akiko; Kawae, Yoshiko; Hatake, Kazue; Nagasaka, Hironori; Tamagawa, Nobuyoshi

    2018-06-21

    Causative mutations cannot be identified in the majority of Asian patients with suspected maturity-onset diabetes of the young (MODY). To elucidate the genetic basis of Japanese patients with MODY-like diabetes and gain insight into the etiology of patients without mutations in the major MODY genes. 263 Japanese patients with early-onset, nonobese, MODY-like diabetes mellitus referred to Osaka City General Hospital for diagnosis. Mutational analysis of the four major MODY genes (GCK, HNF1A, HNF4A, HNF1B) by Sanger sequencing. Mutation-positive and mutation-negative patients were further analyzed for clinical features. Mutations were identified in 103 (39.2%) patients; 57 mutations in GCK; 29, HNF1A; 7, HNF4A; and 10, HNF1B. Contrary to conventional diagnostic criteria, 18.4% of mutation-positive patients did not have affected parents and 8.2% were in the overweight range (BMI >85 th percentile). HOMA-IR at diagnosis was elevated (>2) in 15 of 66 (22.7%) mutation-positive patients. Compared with mutation-positive patients, mutation-negative patients were significantly older (p = 0.003), and had higher BMI percentile at diagnosis (p = 0.0006). Interestingly, maternal inheritance of diabetes was significantly more common in mutation-negative patients (p = 0.0332) and these patients had significantly higher BMI percentile as compared with mutation-negative patients with paternal inheritance (p = 0.0106). Contrary to the conventional diagnostic criteria, de novo diabetes, overweight, and insulin-resistance are common in Japanese patients with mutation-positive MODY. A significant fraction of mutation-negative patients had features of early-onset type 2 diabetes common in Japanese, and non-Mendelian inheritance needs to be considered for these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Impact of early detection and treatment of diabetes on the 6-year prevalence of cardiac autonomic neuropathy in people with screen-detected diabetes

    DEFF Research Database (Denmark)

    Charles, Morten; Fleischer, J; Witte, Daniel Rinse

    2013-01-01

    Baggrund: Der er begrænset viden om hvordan tidlig multifaktoriel behandling forbedrer konsekvenser af diabetes. Kardiel autonom neuropati (KAN) hos personer med diabetes indikerer omfattende skade på det autonome nervesystem og er relateret til mortalitet og livskvalitet. I dette studie fra...... ADDITION Danmark undersøgte vi effekten af tidlig opsporing og efterfølgende intensive behandling af type 2 diabetes i almen praksis på hyppigheden af kardiel autonom neuropati 6 år efter diagnose. Resultater: Prævalensen af tidlig KAN var 15,1% i rutine behandlingsgruppen (RG) og 15.5% i intensive...... kardiovaskulære risikofaktorer er således ikke nok til at forebygge at mange diabetes patienter udvikler KAN....

  6. High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation.

    Directory of Open Access Journals (Sweden)

    Baerbel Klauke

    Full Text Available Cardiomyopathies might lead to end-stage heart disease with the requirement of drastic treatments like bridging up to transplant or heart transplantation. A not precisely known proportion of these diseases are genetically determined. We genotyped 43 index-patients (30 DCM, 10 ARVC, 3 RCM with advanced or end stage cardiomyopathy using a gene panel which covered 46 known cardiomyopathy disease genes. Fifty-three variants with possible impact on disease in 33 patients were identified. Of these 27 (51% were classified as likely pathogenic or pathogenic in the MYH7, MYL2, MYL3, NEXN, TNNC1, TNNI3, DES, LMNA, PKP2, PLN, RBM20, TTN, and CRYAB genes. Fifty-six percent (n = 24 of index-patients carried a likely pathogenic or pathogenic mutation. Of these 75% (n = 18 were familial and 25% (n = 6 sporadic cases. However, severe cardiomyopathy seemed to be not characterized by a specific mutation profile. Remarkably, we identified a novel homozygous PKP2-missense variant in a large consanguineous family with sudden death in early childhood and several members with heart transplantation in adolescent age.

  7. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    International Nuclear Information System (INIS)

    Liu, Chih-Wei; Bramer, Lisa; Computational Modeling); Webb-Robertson, Bobbie-Jo; Computational Modeling); Waugh, Kathleen; Rewers, Marian J.; Zhang, Qibin; Biochemistry)

    2017-01-01

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.

  8. Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran

    Directory of Open Access Journals (Sweden)

    Mitra Javanmardi

    2015-01-01

    Full Text Available Background: Diabetic nephropathy (DN is one of the most important complications of diabetes mellitus. Now-a-days, cystatin C (CysC is introduced as a new marker for diagnosis of renal damages; however, use of this marker in clinical laboratories is still controversial. The present study was aimed to evaluate the diagnostic value of serum CysC for early detection or monitoring treatment of kidney damages in the Kurdish people with type 2 diabetes mellitus. Materials and Methods: Glomerular filtration rate (GFR was estimated by Modification of Diet in Renal Disease formula. Serum CysC and urine microalbumin were also measured in 126 diabetic and healthy subjects. Blood glycated hemoglobin (Hb also measured in all healthy and diabetic patients. Two independent samples t-test, Mann-Whitney U-test, one-way ANOVA, and Kruskal-Wallis test, as well as Pearson/Spearman correlation coefficient statistical tests were used as appropriate. Results: Serum CysC was higher (1312.41 ng/ml in diabetic patients with GFR <60 ml/min than other subjects (993.25 ng/ml (patients with normal kidney function and healthy subjects. A borderline significant correlation between CysC and estimating GFR (rs = −0.16, P = 0.05 but highly significant with microalbumin (rs = 0.22, P = 0.014 was observed. Serum CysC sensitivity, negative and positive predictive values were 100 and 4%. Conclusion: CysC cover variation of GFR and urine microalbumin, but it cannot be used as a surrogating marker of glycated Hb. According to our results, it seems that serum CysC is a useful marker for screening of DN; but it cannot be used for monitoring of treatment in diabetic patients.

  9. Change in cardiovascular risk factors following early diagnosis of type 2 diabetes: a cohort analysis of a cluster-randomised trial

    OpenAIRE

    Black, James A; Sharp, Stephen J; Wareham, Nicholas J; Sandbæk, Annelli; Rutten, Guy EHM; Lauritzen, Torsten; Khunti, Kamlesh; Davies, Melanie J; Borch-Johnsen, Knut; Griffin, Simon J; Simmons, Rebecca K

    2014-01-01

    Background There is little evidence to inform the targeted treatment of individuals found early in the diabetes disease trajectory. Aim To describe cardiovascular disease (CVD) risk profiles and treatment of individual CVD risk factors by modelled CVD risk at diagnosis; changes in treatment, modelled CVD risk, and CVD risk factors in the 5 years following diagnosis; and how these are patterned by socioeconomic status. Design and setting Cohort analysis of a cluster-randomised trial (ADDITION-...

  10. Evidence that children born at early term (37-38 6/7 weeks) are at increased risk for diabetes and obesity-related disorders.

    Science.gov (United States)

    Paz Levy, Dorit; Sheiner, Eyal; Wainstock, Tamar; Sergienko, Ruslan; Landau, Daniella; Walfisch, Asnat

    2017-11-01

    Prematurity is known to be associated with high rates of endocrine and metabolic complications in the offspring. Offspring born early term (37-38 6/7 weeks' gestation) were also shown to exhibit long-term morbidity resembling that of late preterm, in several health categories. We aimed to determine whether early term delivery impacts on the long-term endocrine and metabolic health of the offspring. A population-based cohort analysis was performed, including all term singleton deliveries occurring from 1991 through 2013 at a single regional tertiary medical center. Congenital malformations and multiple pregnancies were excluded. Gestational age upon delivery was subdivided into early term deliveries and deliveries occurring at full term and later (≥39 weeks' gestation, comparison group). Endocrine and metabolic morbidity (including diabetes, obesity, hypoglycemia, hyperlipidemia, and hypothyroidism) of the offspring, up to the age of 18 years, was evaluated according to hospitalization files. Kaplan-Meier survival curves were used to compare cumulative morbidity incidence. A Weibull parametric survival model was used to control for time to event, siblings, and other confounders. During the study period 225,260 term deliveries met the inclusion criteria. Of them, 24% (n = 54,073) occurred at early term. Endocrine and metabolic morbidity was significantly more common in the early term group (0.51% vs 0.41%, P = .003). Specifically, overweight and obesity were more common among the early term group (P = .002). Differences were more prominent among children >5 years, who exhibited higher rates of type 1 diabetes mellitus, as well as obesity, when born at early term (P diabetes, hypertension, labor induction, and Apgar score, early term delivery exhibited an independent association with long-term childhood endocrine and metabolic morbidity of the offspring (adjusted hazard ratio, 1.17; 95% confidence interval, 1.01-1.34) and more so for age >5 years (adjusted hazard

  11. Characterization of phosphorus metabolism in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Auffermann, W.; Chew, W.; Tavares, N.J.; Donnelly, T.; Parmley, W.W.; Chatterjee, K.; Wolfe, C.; Higgins, C.B.

    1988-01-01

    Five patients with dilated cardiomyopathy (ejection fraction, ∼25%) and six normal volunteers were studied with localized, gated P-31 MR spectroscopy at 1.5 T. The typical peaks of adenogine triphosphate (ATP[, phosphocreatine (PCr), phosphodiesters (PD), and peaks attributable to 2,3 diphosphoglycerate, inorganic phosphate, and phosphomonoesters were identified and the areas under each peak numerically integrated after baseline correction. PCr/β-ATP was not significantly lower (1.42 +- 0.06 vs 1.54 +- 0.04), but PD/PCr (1.1 +- 0.02 vs 0.6 +- 0.1) (P ≤ .01) and PD/β-ATP (1.50 +- 0.04 vs 0.97 +- 0.17) (P ≤ .05) were significantly higher in patients with dilated cardiomyopathy compared with normal volunteers. Thus, localized, gated P-31 MR spectroscopy in cardiomyopathic patients identifies abnormal myocardial phosphorus metabolism, which might become useful to monitor noninvasively the response to positive inotropic therapy

  12. The Mutations Associated with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ruti Parvari

    2012-01-01

    Full Text Available Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM. The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes.

  13. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    Science.gov (United States)

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and pr