PLASMA ENDOTHELIN-1 CONCENTRATIONS IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND NONDIABETIC PATIENTS WITH CHRONIC ARTERIAL OBSTRUCTIVE DISEASE OF THE LOWER-LIMBS

Background. Endothelin-1 (ET-1), a vasoconstrictor and mitogenic endot helium-derived peptide, has been considered as a marker for endothelia l damage and potential contributor to the development of the atherogen ic process. Methods. To evaluate the pattern of plasma ET-1 secretion in non-insulin-dependent diabetes mellitus (NIDDM) and nondiabetic pat ients with chronic arterial obstructive disease (CAOD) of the lower li mbs, plasma levels of ET-1 were determined in 12 NIDDM patients (10 me n and 2 women; mean age 63+/-8 years) with CAOD of the lower limbs at Fontaine stage II and in 12 nondiabetic patients (11 men and 1 woman; mean age 62+/-4 years) with comparable arteriopathy. Ten normal subjec ts comprised the control population. Results. The plasma levels of ET- 1 in NIDDM patients with CAOD of the lower limbs were 5.7+/-0.3 pmol/L , which represented a significant (p<0.001) difference from the values in nondiabetic patients with comparable arteriopathy (4.1+/-0.6 pmol/ L) and those in the control group (2.7+/-0.7 pmol/L). Plasma levels of ET-1 showed a significant (p<0.0001) positive correlation with the le vels of fasting insulin in NIDDM patients with CAOD of the lower limbs . Increased plasma ET-1 could reflect a major and/or more diffuse endo thelial cell damage or dysfunction in NIDDM than in nondiabetic patien ts with comparable CAOD of the lower limbs. Augmented mitogenic ET-1 l evels could also have a role both in diabetic and nondiabetic angiopat hy. Conclusions. The positive correlation between ET-1 plasma levels a nd fasting insulin levels in NIDDM patients with CAOD of the lower lim bs suggests that the increased ET-1 release could be related to the au gmented insulin secretion in these patients. Insulin-related overprodu ction of ET-1 could promote the atherogenic process and enhance the va scular tone to a greater extent in NIDDM than in nondiabetic patients with CAOD of the lower limbs.