Relationship between Plasma Endothelin-1 and Glycemic Control in Type 2 Diabetes Mellitus

Abstract

The pathogenesis of the vascular complications of diabetes is controversial, micro- and macroangiopathy being the most common cause of morbidity and mortality in diabetic patients. Endothelial cell damage, thought to occur in diabetic patients, may be an important factor in development of angiopathy . For the last few years, considerable evidence has connected endothelin-1 (ET-1), a strong endothelial-derived vasoconstrictor mitogenic peptide, with various cardiovascular disease states . Plasma ET-1 concentrations were found to be abnormally high in patients with conditions associated with endothelial cell injury, as well as in those with hypertension , congestive heart failure , coronary artery disease, and uremia . Contradictory findings regarding ET-1 levels have been reported in patients suffering from diabetes mellitus . Bertello et al. and Kanno et al. described similar plasma ET-1 levels in both healthy controls and patients with non-insulin-dependent diabetes mellitus (Type 2 diabetes) with and without complications. However, the influence of Type 2 diabetes on plasma endothelin levels was definitely established in patients with advanced atherosclerosis . Recent clinical studies have indicated that the normalization of glycemic control cannot only prevent diabetic microangiopathies, but might possibly avert cardiovascular complications , thus pointing to hyperglycemia as the major causal factor in the development of diabetic vascular complications. Moreover, there are indications that high blood glucose is involved in the pathogenesis of coronary heart disease, being a significant factor in cardiovascular mortality . However, in spite of the significant effects of hyperglycemia, very few studies have dealt with the possible influence of glucose metabolic control on endothelial reactivity in Type 2 diabetic patients. The aims of the present paper were a) to establish the possible relationship between plasma ET-1 levels and Type 2 diabetes by comparing plasma ET-1 concentrations in healthy subjects with those in patients with uncomplicated Type 2 diabetes and b) to determine whether ET-1 levels were related to glucose metabolic control in diabetic patients.