Epigenetics: a molecular link between environmental factors and type 2 diabetes.

Department of Clinical Sciences, Lund University Diabetes Center, Lund University, Malmö, Sweden.
Diabetes (Impact Factor: 8.47). 12/2009; 58(12):2718-25. DOI: 10.2337/db09-1003
Source: PubMed
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    ABSTRACT: Diabetes is a major cause of cardiovascular morbidity and mortality and its prevalence is rapidly increasing worldwide. Despite clear advances in developing effective glucose-lowering drugs, clinical trials have recently shown that intensive glycemic control failed to reduce cardiovascular events in the diabetic population. These findings support the concept that the hyperglycemic environment may be remembered in the cardiovascular system. This phenomenon has been recently defined as “metabolic memory” and may contribute to explain the progression of diabetic vascular complications despite achievement of target HbA1c levels. In this regard, epigenetic changes of DNA/histone complexes are emerging as important modulators of oxidant and inflammatory genes, thus leading to persistent cardiac and vascular dysfunction. Over the last few years, the rapid development of many compounds (i.e. histone deacetylase and histone acetyltransferase inhibitors) able to erase adverse chromatin signatures led to the perception that reverting hyperglycemic damage might be possible and represents an attractive challenge. Here we critically discuss recent evidence supporting the concept that chromatin alterations are key drivers of cardiovascular disease and describe the emerging potential of chromatin modifying agents for the reprogramming of detrimental epigenetic signatures in patients with cardiometabolic disturbances.
    Current Pharmaceutical Biotechnology 01/2015; 16(6). · 2.51 Impact Factor
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    ABSTRACT: The International Diabetes Federation estimates that 316 million people are currently affected by impaired glucose tolerance (IGT). Most importantly, recent forecasts anticipate a dramatic IGT increase with more that 470 million people affected by the year 2035. Impaired insulin sensitivity is major feature of obesity and diabetes and is strongly linked with adverse cardiometabolic phenotypes. However, the etiologic pathway linking impaired glucose tolerance and cardiovascular disease remains to be deciphered. Although insulin resistance has been attributed to inflammatory programs starting in adipose tissue, emerging evidence indicates that endothelial dysfunction may represent the upstream event preceding peripheral impairment of insulin sensitivity. Indeed, suppression of reactive oxygen species-dependent pathways in the endothelium has shown to restore insulin delivery to peripheral organs by preserving nitric oxide (NO) availability. Here we describe emerging theories concerning endothelial insulin resistance, with particular emphasis on the role oxidative stress. Complex molecular circuits including endothelial nitric oxide synthase, prostacyclin synthase, mitochondrial adaptor p66(Shc), nicotinamide adenine dinucleotide phosphate-oxidase oxidase and nuclear factor kappa-B are discussed. Moreover, the review provides insights on the effectiveness of available compounds (i.e., ruboxistaurin, sildenafil, endothelin receptor antagonists, NO donors) in restoring endothelial insulin signalling. Taken together, these aspects may significantly contribute to design novel therapeutic approaches to restore glucose homeostasis in patients with obesity and diabetes.
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    ABSTRACT: Diabetes is increasing in epidemic proportions globally, exhibiting the most striking increase in third world countries with emerging economies. This phenomena is particularly evident in the Middle East and North Africa (MENA) region, which has the highest prevalence of diabetes in adults. The most concerning indirect cost of diabetes is the missed work by the adult population coupled with the economic burden of loss of productivity. The major drivers of this epidemic are the demographic changes with increased life expectancy and lifestyle changes due to rapid urbanization and industrialization. Our focus is to compare MENA region countries, particularly Egypt and Saudi Arabia, in terms of their economic development, labor force diversity and the prevalence of diabetes.
    03/2015; 6(2):304-11. DOI:10.4239/wjd.v6.i2.304

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Nov 11, 2014