Pathogenesis and pathophysiology of accelerated atherosclerosis in the diabetic heart.

It has been established that atherosclerotic coronary artery disease is more frequent and more severe in diabetic compared to non-diabetic subjects, but the reason for the excess risk of developing coronary macroangiopathy in diabetes remains incompletely characterized. Various biochemical mechanisms speculated to being at the "heart" of diabetic cardiac and coronary macroangiopathy are reviewed in the present article. In doing so, this article presents evidence that the labyrinthine interactions of hyperglycemia, insulin resistance, and dyslipidemia in diabetes result in a pro-atherogenic phenotype. Furthermore, the diabetic milieu yields a complex (dys)metabolic environment characterized by chronic inflammation, procoagulability, impaired fibrinolysis, neovascularization abnormalities, and microvascular defects that cumulatively alter blood rheology, artery structure, and homeostasis of the endothelium. The contributory influences of these factors in the pathophysiology of coronary artery disease in diabetes are also discussed.