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In this issue

This paper proposes a new hypothesis according to which the prolonged impact of the early metabolic environment on the development and progression of diabetes-related complications is modulated by a process of metabolic memory. The authors suggest that long before the advent of hyperglycemia, events occur that permanently alter cells, such as endothelial cells, and thus lay the groundwork for the development of both the microvascular and macrovascular complications of diabetes. Large-scale clinical trials have demonstrated that metabolic control achieved early in the course of diabetes substantially reduces development and progression of diabetes and the associated microvascular complications. Additionally, prospective observational studies have demonstrated that concentrations of atherogenic and inflammatory mediators are raised even before the onset of diabetes and contribute significantly to subsequent development of macrovascular complications. Collectively, these data suggest that metabolic memories are stored early in the course of diabetes. The authors believe that insulin suppresses inflammation, glucotoxicity and lipotoxicity and thus plays a pivotal and beneficial role. Comprehensive metabolic control, especially when instituted early, may alter the natural history of diabetic complications by affecting this metabolic memory.