SPECIFIC IMPAIRMENT OF ENDOTHELIUM-DEPENDENT VASODILATION IN SUBJECTSWITH TYPE-2 DIABETES INDEPENDENT OF OBESITY

In subjects with type 2 diabetes in whom an impaired response to an en dothelial-dependent vasodilator has been characterized, the population s have also been at least moderately obese. Obesity has been character ized as an independent predictor of endothelial dysfunction in nondiab etic subjects. We hypothesized that in normotensive subjects with type 2 diabetes compared with age-matched control subjects, 1) endothelium -dependent vasodilation, as demonstrated by the forearm blood flow (FA BF) response to intraarterial acetylcholine, would be decreased; 2) en dothelium-independent vasodilation, as demonstrated by the FABF respon se to intraarterial nitroprusside, would be similar; 3) the degree of insulin resistance, as measured by the insulin sensitivity index (S-I) , would predict greater impairment in the FABF response to acetylcholi ne; and 4) these relationships would be independent of obesity. We mea sured FABF by venous occlusion plethysmography during brachial arteria l infusions of the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator nitroprusside in 20 control a nd 17 subjects with type 2 diabetes. We measured S-I using the frequen tly sampled iv glucose tolerance test. Among the diabetic relative to the control subjects we identified a decrease in the acetylcholine-med iated percent increase in FABF (P = 0.02). Using the absolute FABF res ponse to acetylcholine and including adjustments for body mass index a nd other covariates, the overall group difference remained and was not ed to be greatest in those subjects who had lower baseline FABFs. In c ontrast, no significant difference in the nitroprusside-mediated incre ase in the percent change FABF was identified between groups (P = 0.30 ). Finally, the degree of insulin resistance, as measured by S-I, did not independently predict greater impairment of the FABF response to a cetylcholine. This study is the first to identify specific endothelial cell dysfunction that remains significant after adjustment for obesit y in a population of normotensive subjects with type 2 diabetes.