Postprandial hyperglycemia induces vascular endothelial dysfunction by increasing lipid peroxidation and asymmetric dimethylarginine in healthy men.

Abstract

Acute hyperglycemia (AH) increases cardiovascular disease risk by generating reactive oxygen species and disrupting nitric oxide (NO) homeostasis. We hypothesized that AH induces vascular endothelial dysfunction (VED) by increasing oxidative stress and asymmetric dimethylarginine (ADMA), a methylated metabolite of arginine (ARG) that competitively inhibits ARG from binding to NO synthase (NOS). A randomized, crossover study was conducted in healthy men (n = 16; 21.6 ± 0.8 y; 28.9 ± 2.0 kg/m2) who ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma ARG, ADMA, malondialdehyde (MDA), and antioxidants were measured during the 3 h postprandial period. Only glucose ingestion caused AH (P<0.05). FMD decreased at 30–90 min following glucose, but not fructose ingestion. MDA was exacerbated by glucose ingestion (AUC0–3 h 180±8.3 vs. 220±7.4 μM•min). Ascorbic acid and tocopherols were unaffected by both treatments. ARG decreased time-dependently in both trials and to a greater extent in the glucose trial. ADMA/ARG AUC0–3 h was greater in the glucose trial compared to fructose trial. ADMA/ARG was not correlated with MDA, suggesting that NOS inhibition by ADMA is independent of AH-mediated oxidative stress. Thus, AH induces VED by increasing lipid peroxidation and possibly inhibiting NO synthesis from NOS by ADMA. Support provided by ILSI. Grant Funding Source: Internation Life Science Institute