Endocrine Abstracts

Large randomized studies have established that early intensive glycemic control reduces the risk of diabetic complications, both micro and macrovascular. However, epidemiological and prospective data support a long-term influence of early metabolic control on clinical outcomes. This phenomenon has recently been defined as ‘Metabolic Memory.’ It was first hypothesized by Brownlee (Nature 2000), and since shown by many researchers that overproduction of free radicals, superoxide anion (O₂^−•) in particular, forms the unifying link between hyperglycemia and the complications of diabetes. It has also been shown that antioxidant molecules can at least partially reverse these complications both in the laboratory bench and clinically.

In this study we have confirmed in three different models (human endothelial cells, retinal cells and retina from diabetic animals) that, even normalizing glycemia, a persitent activation of many pathways involved in the pathogenesis of diabetic complications is still present. However, the major finding has been the demonstration that even normalizing glycemia an overproduction of free radicals is still evident and, overall, that inhibiting their production, particularly at the mitochondrial level, can switch off the memory’ effect of hyperglycemia.

These findings clearly open a new field of research, aiming to obtain specific compounds able of blocking the ‘Metabolic Memory’.