The early effects of elevated glucose on endothelial function as a target in the treatment of type 2 diabetes.

As predicted by the World Health Organization, the worldwide increase in the incidence of both type 1 and type 2 diabetes will result in a global increase in the impact of cardiovascular disease on human health. Both type 1 and type 2 diabetes are associated with the inability of the body to maintain appropriate levels of blood glucose. Hyperglycemia occurs when blood levels of glucose rises significantly above 5.5 mM and has been clearly linked, in particular, to microvascular complications such as retinopathy and nephropathy. Both acute and chronic hyperglycemia can result in the activation of a number of pro-oxidative and pronitrosoactive pathways. These events are activated by nuclear factor-kappa B (NF-kappabeta), protein kinase C (PKC) and nuclear enzyme poly (ADP-ribose) polymerase. Chronic hyperglycemia also results in the formation of advanced-glycation end products (AGEs). Data also indicates that repetitive postprandial hyperglycemia may have greater pathophysiological consequences than persistent hyperglycemia thus emphasizing the importance of preventing, or rapidly reducing, prandial-induced rises in blood glucose. The recognition that the prediabetic state reflects a postprandial disorder can help identify people with prediabetes and reduce the impact of diabetes-related cardiovascular morbidity and mortality. This review emphasizes strategies designed to minimize the impact of acute effects of hyperglycemia on vascular function.