Hyperhomocysteinemia and impaired vasomotor function in type 2 diabetes mellitus

Abstract

Background: Hyperhomocysteinemia has been shown to adversely affect vascular function. The aim of this study was to determine whether hyperhomocysteinemia was independently associated with changes in endothelium-dependent and -independent vasomotor functions in patients with type 2 diabetes mellitus. Materials and methods: Fasting homocysteine (tHcy) was measured in 123 patients with type 2 diabetes and in 61 nondiabetic controls. Endothelium-dependent and -independent vasodilation was measured using high-resolution vascular ultrasound. Results: Plasma tHcy concentration was increased in the diabetic patients (11.1 ± 3.7 μmol L-1 vs. 9.8 ± 2.9, P < 0.05). The prevalence of hyperhomocysteinemia (defined as tHcy > 15 μmol L-1) was higher in the diabetic patients (P < 0.05). Within group comparisons showed that both the abnormalities in endothelium-dependent and -independent vasodilation were significantly more severe in diabetic patients with tHcy 10-15 (P < 0.05) and tHcy > 15 μmol L-1 (P < 0.05) than in those patients with tHcy < 10 μmol L-1. When compared with nondiabetic controls matched for tHcy levels, impairment of endothelium-dependent and -independent vasodilation were already evident, even in patients with normal tHcy levels (P < 0.01). Despite significant univariate relationships between tHcy and endothelium-dependent (r = -0.24, P < 0.01) and -independent vasodilation (r = -0.33, P < 0.01) in patients with diabetes, only the relationship between tHcy and endothelium-independent vasodilation remained significant after adjusting for other cardiovascular risk factors in multiple regression analysis. Conclusions: Impairment of endothelium-dependent and -independent vasodilation was already present in diabetic patients with normal tHcy levels, and these abnormalities became more severe with increasing tHcy levels. Only the association between tHcy and endothelium-independent vasodilation was free of other cardiovascular risk factors.