Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery

OBJECTIVES We examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading. BACKGROUND Endothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially. METHODS With ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with, normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate. RESULTS Flow-mediated vasodilation decreased after glucose loading (NGT: 7.53 +/- 0.40, 4.24 +/- 0.28 and 6.35 +/- 0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50 +/- 0.48, 1.40 +/- 0.41** and 4.00 +/- 0.47*, respectively;, DM: 4.77 +/- 0.37, 1.35 +/- 0.38** and 1.29 +/- 0.29%**, respectively; *p < 0.01 vs. fasting, **p < 0.005 vs, fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43 +/- 0.07, 2.03 +/- 0.12 and 1.80 +/- 0.12, respectively; IGT: 1.65 +/- 0.11, 2.46 +/- 0.12** and 1.94 +/- 0.08*, respectively; DM: 1.73 +/- 0.07, 2.34 +/- 0.08** and 2.47 +/- 0.09** nmol/ml, respectively; *p < 0.05 vs. fasting, **p < 0.01 vs, fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups. CONCLUSIONS Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis. (C) 1999 by the American College of Cardiology.