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

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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.




Kawano, H., Motoyama, T., Hirashima, O., Hirai, N., Miyao, Y., Sakamoto, T., … Yasue, H. (1999). Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. Journal of the American College of Cardiology, 34(1), 146–154. https://doi.org/10.1016/S0735-1097(99)00168-0

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