IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Background. Endothelium-dependent vasodilation is abnormal in experimental models of diabetes mellitus. We postulated that abnormalities of endothelial function are also present in patients with insulin-dependent diabetes mellitus and may contribute to the pathogenesis of vascular disease in these individuals. Methods and Results. Vascular reactivity was measured in the forearm resistance vessels of 15 patients with insulin-dependent diabetes mellitus and 16 age-matched normal subjects. No patient had hypertension or dyslipidemia. Each subject was pretreated with aspirin to inhibit endogenous production of prostanoids. Methacholine chloride (0.3 to 10 mu g/min) was administered via the brachial artery to assess endothelium-dependent vasodilation. Sodium nitroprusside (0.3 to 10 mu g/min) and verapamil (10 to 300 mu g/min) were infused intra-arterially to assess endothelium-independent vasodilation; phenylephrine (0.3 to 3 mu g/min) was administered to examine vasoconstrictor responsiveness. Forearm blood flow was determined by venous occlusion plethysmography, and dose-response curves were generated for each drug. Basal forearm blood flow in diabetic and normal subjects was comparable (2.6+/-0.2 versus 2.1+/-0.3 mL.100 mL(-1).min(-1), respectively; P=NS). The forearm vasodilative response to methacholine was less in diabetic than in normal subjects. At the highest dose of methacholine, the forearm blood flow increased 9.5+/-1.1 mL.100 mL(-1).min(-1) in diabetic subjects and 15.3+/-1.4 mL.100 mL(-1).min(-1) in normal subjects (P<.01). The forearm blood flow responses to nitroprusside and verapamil and the forearm vasoconstricter responses to phenylephrine were similar in diabetic and healthy subjects. In diabetic subjects, endothelium-dependent vasodilation correlated inversely with serum insulin concentration but not with glucose concentration, glycosylated hemoglobin, or duration of diabetes. Conclusions. Endothelium-dependent vasodilation is abnormal in forearm resistance vessels of patients with insulin-dependent diabetes mellitus. This abnormality may be relevant to the high prevalence of vascular disease that occurs in these individuals.