Acute Hyperhomocysteinemia Impairs Endothelium Function in Subjects with Type 2 Diabetes Mellitus

The objective of the present study was to examine the effect of acute, methionine-induced hyper-homocysteinemia (HHCY) on endothelial function and indices of arterial stiffness in subjects with type 2 diabetes mellitus (T2DM). A total of 30 subjects with T2DM, free of macrovascular disease were examined in a crossover study. L-methionine (M) (0.1 g/kg) and water (W) load were given in random order with an interval of about 1 week in between. Endothelial function was assessed by flow-mediated vasodilation (FMD). Arterial stiffness was assessed by determination of augmentation index (AI). Measurements were performed in the fasting state, 1, 2 and 3 h after the M or the W load. Total plasma homocysteine (HCY) levels did not change after W administration, while M administration resulted in a significant increase in HCY concentrations at 3 h. FMD throughout the experiment expressed as area under the curve (AUC) was significantly lower after the M than after the W load. Consistent with impairment in endothelial function, the AUC of AI was significantly higher after the M than after the W administration. Acute HHCY impairs endothelial function and increases arterial stiffness in patients with T2DM. This effect is probably mediated by a reduction of nitric oxide bioavailability in endothelium.