Plasma levels of endothelin, lipid peroxides and prostacyclin in diabetic patients with macroangiopathy

Abstract

The prevalence of macroangiopathy is increased in diabetes mellitus. Endothelial cell injury is thought to be an early event leading to atherosclerosis which may be initiated by several factors. We have investigated the relationship between plasma endothelin, lipid peroxide (measured as thiobarbituric acid reacting species (TBARS)) and 6-keto-prostaglandin-F 1A (6-keto-PG-F 1A) in Type 2 diabetic patients with macroangiopathy. Fifty-three diabetic subjects with macroangiopathy were investigated, together with 50 diabetic and 50 control subjects without evidence of vascular disease. Both the endothelin and TBARS levels were significantly higher in diabetic patients with macroangiopathy (10.8 (8.0–14.4) pmol/l and 5.6 (3.2–9.7) μmol/l, respectively) compared with control subjects (7.6 (5.0–11.0) pmol/l and 4.5 (3.0–6.4) μmol/l, P<0.001) and with diabetic subjects without macroangiopathy (7.4 (4.9–11.2) pmol/l ( P<0.001) and 4.9 (3.0–8.0) μmol/l ( P<0.05)). 6-Keto-PG-F 1A levels were significantly decreased in diabetic subjects with macroangiopathy 209 (123–355) pg/ml than in normal subjects 241 (137–425) pg/ml, ( P<0.05) and diabetic subjects without macroangiopathy 224 (162–309) pg/ml, ( P<0.05). Comparison of levels of endothelin with those of TBARS in macroangiopathy group, showed that endothelin is a more consistent marker of the atherogenic process ( P<0.01). In conclusion, we have shown that there are abnormalities of endothelium-derived factors in diabetic patients with macroangiopathy, mainly in endothelin. Furthermore, in this group there was a positive correlation between endothelin and fasting insulin levels.