ENDOTHELIN-1 AND BIG ENDOTHELIN-1 IN NIDDM PATIENTS WITH AND WITHOUT MICROANGIOPATHY

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 an d big endothelin-1, a precursor peptide of endothelin-1, in 33 untreat ed patients with noninsulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentratio ns in 18 patients with microangiopathy, in 15 patients without microan giopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endoth elin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation be tween plasma levels of endothelin-1 or big endothelin-1 and fasting bl ood glucose, HbA(1c), mean blood pressure, or period of duration of di abetes mellitus in the patient groups. The results indicate that eleva tion of plasma big endothelin-1 levels with diminished conversion of b ig endothelin-1 to endothelin-1 is associated with diabetic microangio pathy, which may be the effect rather than the cause of endothelial dy sfunction.