Effects of Acute Hyperglycemia on Endothelium-Dependent Vasodilation in Patients with Diabetes Mellitus or Impaired Glucose Metabolism

ABSTRACT

BACKGROUND: Although impaired endothelial function is well known in patients with diabetes mellitus, the precise mechanism and the factors that contribute to this dysfunction remain to be clarified. We examined the effect of acute hyperglycemia on patients with impaired glucose metabolism in vivo by plethysmography. METHODS: Seven patients with diabetes mellitus or impaired glucose metabolism were studied. In each patient, endothelial function was examined in the fasting state and at two levels of hyperglycemia, which were achieved by the infusion of glucose, insulin, and somatostatin. Forearm blood flow was measured while acetylcholine was infused in increasing concentrations(7.5, 15, and 30 microgram/min) through the brachial artery. RESULTS: Glucose concentrations increased accordingly at each stage, from 135.3+/-18.4 mg/dl at stage 1(the fasting state), to 239.0+/-15.2 mg/dl at stage 2(the first level of hyperglycemia), and to 378.3+/-25.3 at stage 3 (the second level of hyperglycemia) [p<0.01]. Maximal acetylcholine-dependent vasodilation achieved by infusion of acetylcholine at 30 microgram/min was significantly aftenuated during stages 2 and 3 compared with stage 1(p<0.05 by AVOVA; forearm blood flow ratio was 2.87+/-0.18 and 2.56+/-0.14 versus 3.58+/-0.21, respectively). This was also evident during the infusion of 15 microgram/min and 7.5 microgram/min of acetylcholine. CONCLUSIONS: Endothelium-dependent vasodilation is significantly aftenuated by acute hyperglycemia in patients with diabetes mellitus or impaired glucose metabolism. Our findings suggest that elevated glucose may contribute to the endothelial dysfunction observed in patients with diabetes mellitus or impaired glucose metabolism.