Effect of the postprandial state on nontraditional risk factors

Hyperglycemia is the cause of chronic microvascular complications in diabet es. Increased macrovascular disease occurring in diabetes is multifactorial , with hyperglycemia being only 1 of the factors responsible. A major defic iency in our understanding of the role of hyperglycemia in the pathogenesis of chronic diabetic complications is the contribution made by exaggerated postprandial glycemic excursions, in contrast to that made by chronic fasti ng hyperglycemia. Hyperglycemia is thought to cause chronic diabetic compli cations through greater than or equal to1 of the following biochemical mech anisms: (1) an exaggerated polyol pathway, (2) protein glycation and the fo rmation of advanced glycation end products, (3) excessive activation of pro tein kinase C (PKC) isoenzymes in vascular and mesangial cells, and (4) gre ater oxidative stress. The focus of this article is how postprandial hyperg lycemia and glucose excursions might specifically activate greater than or equal to1 of these mechanisms and how they might contribute to the developm ent of the chronic complications of diabetes by causing endothelial dysfunc tion, a procoagulant state, carbonyl stress, and/or vascular and oxidative effects secondary to PKC activation. (C) 2001 by Excerpta Medica, Inc.