Clinical Factors Associated With Resistance to Microvascular Complications in Diabetic Patients of Extreme Disease Duration: The 50-year Medalist Study

Harvard University, Cambridge, Massachusetts, United States
Diabetes care (Impact Factor: 8.42). 09/2007; 30(8):1995-7. DOI: 10.2337/dc06-2222
Source: PubMed
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Available from: Lloyd Paul Aiello
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    • "There is also an increasing body of evidence to suggest that memory of early hyperglycaemic exposure can be retained in target cells that could subsequently alter gene expression patters even under euglycaemic conditions [27,31-35]. As broadly shown in epidemiological studies and trials, good glycaemic control could not prevent diabetes progression and associated vascular complications in most diabetic patients and early prevention of hyperglycaemia is more important in prevention of diabetes complications [36-39]. Our results, which are consistent with these studies, indicate that aberrant DNA methylation alterations might occur in response to a chronic hyperglycaemic environment rather than glucose fluctuations that arisen by glycaemic control. "
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    ABSTRACT: The aim of this study was to evaluate whether global levels of DNA methylation status were associated with albuminuria and progression of diabetic nephropathy in a case-control study of 123 patients with type 2 diabetes- 53 patients with albuminuria and 70 patients without albuminuria. The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood mononuclear cells to determine individual global DNA methylation status in two groups. Global DNA methylation levels were significantly higher in patients with albuminuria compared with those in normal range of albuminuria (p = 0.01). There were significant differences in global levels of DNA methylation in relation to albuminuria (p = 0.028) and an interesting pattern of increasing global levels of DNA methylation in terms of albuminuria severity. In patients with micro- and macro albuminuria, we found no significant correlations between global DNA methylation levels and duration of diabetes (p > 0.05). In both sub groups, there were not significant differences between global DNA methylation levels with good and poor glycaemic control (p > 0.05). In addition, in patients with albuminuria, no differences in DNA methylation levels were observed between patients with and without other risk factors including age, gender, hypertension, dyslipidaemia and obesity. These data may be helpful in further studies to develop novel biomarkers and new strategies for clinical care of patients at risk of diabetic nephropathy.
    Full-text · Article · Jun 2014 · Journal of Diabetes and Metabolic Disorders
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    • "The strongest risk factors for diabetic micro vascular complications are poor glycemic control and diabetes duration. It is notified, despite good glycemic control, vascular complications remain in most diabetic patients [1,2]. In addition, diabetic complications may develop before diagnosis [3,4]. "
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    ABSTRACT: Background The aim of this study was assessment of predictive factors of diabetic retinopathy. Methods A cross-sectional study was designed by recruiting 1228 type 2 diabetic patients from a diabetes referral clinic over a six-month period (from July to December, 2012). Diabetes risk factors, complications, laboratory results have been recorded. Results Of the 1228 diabetic patients (54% women, mean age 58.48 ± 9.94 years), prevalence of diabetes retinopathy was 26.6%. There were significant associations between retinopathy and family history of diabetes (p = 0.04), hypertension (p = 0.0001), diabetic duration (p = 0.0001), poor glycemic control (p = 0.0001) and age of onset of diabetes (p = 0.0001). However, no significant associations were found between retinopathy with dyslipidemia and obesity. In logistic regression model, poor glycemic control (p = 0.014), hypertension (p = 0.0001), duration of diabetes (p = 0.0001) and family history of diabetes (p = 0.012) independently predicted retinopathy after adjustment for age and sex. Conclusions Diabetic complications are resulting from an interaction from genes and environmental factors. A family history of diabetes is pointing toward a possible genetic and epigenetic basis for diabetic retinopathy. Our findings suggest the role of epigenetic modifications and metabolic memory in diabetic retinopathy in subjects with family history of diabetes.
    Full-text · Article · May 2014 · Journal of Diabetes and Metabolic Disorders
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    • "Beside this, it is important to note that hyperglycemia alone may not be sufficient to trigger diabetic complications . Significant numbers of type 1 diabetic patients live without severe complications regardless of their classical markers thought to be predictive for diabetic vascular complications suggesting that some genetic factors can neutralize the adverse effects of hyperglycemia [21]. Oxidative stress is recognized as a key participant in the development of vascular diabetic complications [13]. "
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    ABSTRACT: Diabetes mellitus (DM) is a complex syndrome which leads to multiple dysfunctions including vascular disorders. Hyperglycemia is considered to be a key factor responsible for the development of diabetic vascular complications and can mediate their adverse effects through multiple pathways. One of those mechanisms is the activation of protein kinase C (PKC). This important regulatory enzyme is involved in a signal transduction of several vascular functions including vascular smooth muscle contractility. Many studies have shown that hyperglycemia in DM results in oxidative stress. Overproduction of reactive oxygen species (ROS) by different oxidases and the mitochondrial electron transport chain (ETC), advanced glycation end products, polyol pathway flux, and hyperglicemia-induced rising in diacylglycerol (DAG) contribute to the activation of PKC. Activation of endothelial PKC in DM leads to endothelium-dependent vasodilator dysfunction. The main manifestations of this are inhibition of vasodilatation mediated by nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin, and activation of vasoconstriction mediated by endothelin-1 (ET-1), prostaglandin E2 (PGE2) and thromboxane A2 (TXA2). Activated PKC in DM also increases vascular endothelial growth factor (VEGF) expression and activates NADPH oxidases leading to raised ROS production. On the other hand, PKC in DM is involved in enhancement of vascular contractility in an endothelium-independent manner by inactivation of K(+) channels and Ca(2+) sensitization of myofilaments in vascular smooth muscle cells. This shows that PKC is a potential therapeutic target for treating vascular diabetic complications.
    Full-text · Article · Apr 2014 · International journal of cardiology
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