The Role of Metabolic Memory in Diabetes Mellitus

Abstract

Diabetes Mellitus, is an important public health problem that causes increased morbidity and mortality. Hyperglycemia, specific sign of diabetes; tried to be controlled clinically exogenous insulin administration or various drugs however, despite developments treatment and follow-up, development of vascular complications hasn’t been completely prevented in many diabetic patients. Several epidemiological, comprehensive studies have shown that early-intensive control of hyperglycemia reduces risk of diabetes-related complications. These studies emphasize need for early glycemic control. Early control of hyperglycemia has recently been defined as "metabolic memory". Different mechanisms, such as overproduction of free oxygen radicals in mitochondria and endothelial cells, mitochondrial deoxyribonucleic acid (DNA) damage, protein kinase C activation, polyol-hexosamine pathway activation, increased production of advanced glycation end products (AGEs) and AGE receptor overexpression play an important role in metabolic memory pathogenesis. These mechanisms induce gene expression permanently and causing epigenetic changes. Metabolic memory occurs through epigenetic changes such as histone modification, DNA methylation and micro-ribonucleic acid (RNA)-related mechanisms. From a clinical point of view, metabolic memory theory emphasizes necessity of an early-intensive treatment regimen to achieve metabolic control as soon as possible. In addition to early intensive hyperglycemia control, therapeutic agents or epigenetic therapy can reduce reactive oxygen species and glycosylation also be used in order to minimize long-term diabetic complications. In this review, metabolic memory theory, definition and pathogenesis of metabolic memory, epigenetic mechanisms and therapeutic approaches are evaluated.