Carotid Atherosclerosis in Type 2 Diabetes Mellitus: Potential Role of Endothelin-1, Lipoperoxides, and Prostacyclin

Abstract

Factors were studied that may initiate macroangiopathy or enhance or aggravate its patho genesis in patients with type 2 diabetes mellitus. A total of 151 diabetics were compared with healthy controls (n = 50); all patients and subjects were normotensive and without renal failure. Plasma endothelin-1 and free radical levels were measured. In addition, plasma prosta cyclin levels were assessed by assaying its stable, spontaneous, breakdown product 6-keto prostaglandin-F1a. Diabetics were divided into three groups: those with clinically evident macroangiopathy and those with early or without atherosclerosis (as determined by the carotid intima-media thickness. Plasma endothelin-1 levels were increased in all diabetics with atherosclerosis. Plasma free radical levels were increased in diabetics with macroan giopathy when compared with control subjects. The plasma levels of 6-keto-prostaglandin-F 1a were slightly, but significantly, decreased in the diabetics with macroangiopathy when compared with control subjects. The carotid intima-media thickness was significantly greater in diabetics without macroangiopathy when compared with the controls. Furthermore, the intima-media thickness increased significantly in this group of diabetics but not in the controls over a 30-month follow-up period. Several factors may contribute to atherogenesis in diabetics. These include increased plasma endothelin-1 and free radical levels as well as a defi ciency of prostacyclin. These factors may become targets for intervention as well as markers of disease progression.