Epigenetics: deciphering its role in diabetes and its chronic complications

1. Increasing evidence suggests that epigenetic factors might regulate the complex interplay between genes and the environment, and affect human diseases, such as diabetes and its complications. 2. Clinical trials have underscored the long lasting beneficial effects of strict glycaemic control for reducing the progression of diabetic complications. They have also shown that diabetic complications, such as diabetic nephropathy, a chronic kidney disorder, can continue even after blood glucose normalization, suggesting a metabolic memory of the prior glycaemic state. 3. Dysregulation of epigenetic post-transcriptional modifications of histones in chromatin, including histone lysine methylation, has been implicated in aberrant gene regulation associated with the pathology of diabetes and its complications. Genome-wide studies have shown cell-type specific changes in histone methylation patterns under diabetic conditions. In addition, studies in vascular cells have shown long lasting changes in epigenetic modifications at key inflammatory gene promoters after prior exposure to diabetic conditions, suggesting a possible mechanism for metabolic memory. 4. Recent studies have shown roles for histone methylation, DNA methylation, as well as microRNA in diabetic nephropathy. Whether these epigenetic factors play a role in metabolic memory of diabetic kidney disease is less well understood. 5. The incidence of diabetes is growing rapidly, as also the cost of treating the resulting complications. A better understanding of metabolic memory and the potential involvement of epigenetic mechanisms in this phenomenon could enable the development of new therapeutic targets for the treatment and/or prevention of sustained diabetic complications.