Pathophysiology of vascular disease in diabetes: effects of gliclazide.

Diabetes mellitus is a major risk factor for coronary heart disease, peripheral vascular disease, and cardiovascular disease. The prevalence of these complications is increased about two- to four-fold in people with diabetes in the United States, and they contribute substantially to morbidity, mortality, and healthcare costs. The pathogenesis of macrovascular disease in diabetes is multifactorial. Endothelial injury is an early event, followed by macrophage adherence and uptake of lipids to produce a fatty streak. Platelet adherence, aggregation, and release of thromboxane and platelet-derived growth factors may then occur. Quantitative and qualitative alterations of lipoproteins are seen, particularly in uncontrolled insulin-dependent and non-insulin-dependent diabetes. Hyperinsulinemia may be contributory, as may elevated plasma proinsulin levels. Glycation of plasma proteins and of components of the vascular wall occurs, and altered coagulation and/or fibrinolysis may lead to thrombosis. The process is accelerated by hypertension, smoking, and hypercholesterolemia. Gliclazide is an oral sulfonylurea agent that has been reported to have actions on platelet function and fibrinolysis in addition to its effects on glycemia. The evidence for this is reviewed, and recommendations for future studies are made.