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 patients with atherosclerosis as well as in patients with non-insulin-dependent diabetes mellitus (NIDDM) suggesting a role in the pathogenesis of these disorders. The aim of the present study was to ascertain the influence of the NIDDM on plasma ET-1 levels in patients with advanced 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. Twenty-two healthy subjects (43.1 +/- 18.3 years) served as controls. Circulating ET-1 levels were higher in NIDDM patients (6.8 +/- 2.8 pg/mL) than both controls (3.1 +/- 1 pg/mL; p < 0.001) and patients with vascular disease but without NIDDM (4.7 +/- 1.6 pg/mL; p < 0.04). No significant relationship was found between age and ET-1 concentrations, and no differences were noted between men and women in the control group. This study demonstrated that circulating ET-1 levels are increased in patients with atherosclerosis and that those with NIDDM showed the highest ET-1 levels. These observations strongly support a role for ET-1 in the pathogenesis of atherosclerosis and also suggest that this peptide may be involved in the development of atherosclerotic lesions in the NIDDM. We speculated that chronic exposure to hyperinsulinemia and hypertriglyceridemia in the diabetic patients could account for the increased ET-1 levels found in these patients.