INFLUENCE OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS ON PLASMA ENDOTHELIN-1 LEVELS IN PATIENTS WITH ADVANCED ATHEROSCLEROSIS

Endothelin-1 (ET-1) is an endothelium-derived vasoactive peptide with mitogen properties. Increased circulating ET-1 levels were found in pa tients with atherosclerosis as well as in patients with non-insulin-de pendent diabetes mellitus (NIDDM) suggesting a role in the pathogenesi s of these disorders. The aim of the present study was to ascertain th e influence of the NIDDM on plasma ET-1 levels in patients with advanc ed atherosclerotic lesions. The circulating ET-1 levels were measured in 16 NIDDM patients (68.4 +/- 8.4 years) with macroangiopathy and in ten patients (65.3 +/- 11 years) with atherosclerosis without NIDDM. T wenty-two healthy subjects (43.1 +/- 18.3 years) served as controls. C irculating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8 pg/m L) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with v ascular disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No si gnificant relationship was found between age and ET-1 concentrations, and no differences were noted between men and women in the control gro up. This study demonstrated that circulating ET-1 levels are increased in patients with atherosclerosis and that those with NIDDM I showed t he highest ET-1 levels. These observations strongly support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest that thi s peptide may be involved in the development of atherosclerotic lesion s in the NIDDM. We speculated that chronic exposure to hyperinsulinemi a and hypertriglyceridemia in the diabetic patients could account for the increased ET-1 levels found in these patients. (C) 1998 Elsevier S cience Inc.