Metabolic memory in diabetes--focus on insulin.

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 atherogenic and inflammatory mediators are elevated even prior to the onset of diabetes and significantly contribute to subsequent development of macrovascular complications. Collectively, these data suggest that metabolic memories are stored early in the course of diabetes. We believe that insulin suppresses inflammation and also suppresses glucotoxicity and lipotoxicity (and the consequences thereof, such as the formation of advanced glycation end products and epigenetic phenomena), and thus has 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. Thus, our overall goal is to understand in more detail the molecular mechanisms involved in these changes, thereby affording us opportunities to reduce the long-term effects of diabetes. Copyright 2005 John Wiley & Sons, Ltd.