Defective vasodilation response to exercise in cutaneous precapillary vessels in diabetic humans

Although anatomic abnormalities in capillary structure are well described in diabetes mellitus, physiologic responses of diabetic microcirculation are less clear. This study addresses whether cutaneous vasodilation occurs normally in diabetic subjects in response to a standard exercise of underlying muscle. The methods involve a washout analysis from forearm skin of the fast-moving isotope 133Xe and the diffusion-limited marker 111In-diethylenetriamine pentaacetic acid. Twenty-four normotensive type II diabetic patients of age (mean +/- SE) 59 +/- 1.4 yr were age and weight matched with 24 controls. Control subjects increased flow 50.6 +/- 6.4%, which was not different from the increase in diabetic subjects of 52.7 +/- 7.6%. Permeability-surface-area product (PS) increased in control subjects from 1.77 +/- 0.20 ml.min-1.100 g-1 to 3.79 +/- 0.50 (2P = .0001), whereas diabetic subjects did not show a change in PS (3.29 +/- 0.35 to 2.69 +/- 0.31). Resting PS was higher in diabetic than control subjects (P = .0003), perhaps indicating an already recruited capillary bed. During repetitive exercise, control subjects increased capillary density 125 +/- 27% (2P = .0001) above basal with a nonsignificant 14 +/- 8.4% decrease in mean capillary blood flow. Diabetic subjects responded with a nonsignificant decrease in capillary density and a significant 139 +/- 38% increase in capillary blood flow (2P = .001). It is concluded that, although overall vasodilation occurs normally in diabetic cutaneous circulation, the mechanism is different from the normal response in that flow increases by augmentation of capillary flow rather than by recruitment. This is consistent with the thesis promulgated by others that diabetic precapillary vessels have depressed vasodilatory responses or are already maximally vasodilated. The ability of diabetic subjects to vasodilate by augmentation was not correlated with years of diabetes or use of insulin and only slightly negatively correlated with random blood glucose levels (r = -.423, P less than .05).