Impairment of insulin-induced vasodilation is associated with muscle insulin resistance in type 2 diabetes.

To clarify the association between the actions of insulin on the vascular wall and on the muscles in diabetes, we evaluated insulin-mediated vasodilation and muscle glucose uptake simultaneously using the euglycemic hyperinsulinemic glucose clamp technique and the calculation of total peripheral vascular resistance (TPR) from arterial pulse wave analysis in 19 Japanese patients with type 2 diabetes who had no signs of atherosclerosis. During the clamp study, the plasma norepinephrine (NE) level and plasma renin activity (PRA) increased without showing any significant correlation to the glucose infusion rate (GIR); a marker of muscle insulin sensitivity, and no changes of other plasma vasoactive hormone levels were observed. TPR decreased over time during the clamp study. The decrease of TPR from baseline was 0.88 +/- 0.02 at 1 h (mean +/- S.E.M., P < 0.01) and 0.79 +/- 0.03 at 2 h (P < 0.01), and the relative change in TPR from baseline was negatively correlated with GIR (r = -0.48 at 1 and 2 h; both P < 0.05). Our results suggest that there is also insulin resistance in the vascular wall, and this phenomenon may be associated with muscle insulin resistance in type 2 diabetes.