Folic Acid: A Marker of Endothelial Function in Type 2 Diabetes?

OBJECTIVES: Endothelial dysfunction is a common feature of type 2 diabetes. Recent studies suggest that the B-vitamin folic acid exerts direct beneficial effects on endothelial function, beyond the well known homocysteine lowering effects. Therefore, folic acid might represent a novel “biomarker” of endothelial function. We sought to determine whether plasma levels of folic acid determine endothelial-dependent vasodilation in patients with type 2 diabetes. METHODS: Forearm arterial blood flow (FABF) was measured at baseline and during intrabrachial infusion of the endothelial-dependent vasodilator acetylcholine (15 μg/min) and the endothelial-independent vasodilator sodium nitroprusside (2 μg/min) in 26 type 2 diabetic patients (age 56.5 ± 0.9 years, means ± SEM) with no history of cardiovascular disease. RESULTS: FABF ratio (ie, the ratio between the infused and control forearm FABF) significantly increased during acetylcholine (1.10 ± 0.04 vs 1.52 ± 0.07, p < 0.001) and sodium nitroprusside (1.12 ± 0.11 vs 1.62 ± 0.06, p < 0.001) infusions. After correcting for age, gender, diabetes duration, smoking, hypertension, body mass index, microalbuminuria, glycated hemoglobin, low-density lipoprotein cholesterol, and homocysteine, multiple regression analysis showed that plasma folic acid concentration was the only independent determinant (p = 0.037, R(2) = 0.22) of acetylcholine-mediated, but not sodium nitroprusside-mediated, vasodilatation. CONCLUSIONS: Folic acid plasma concentrations determine endothelium-mediated vasodilatation in patients with type 2 diabetes. These results support the hypothesis of a direct effect of folic acid on endothelial function and the rationale for interventions aimed at increasing folic acid levels to reduce cardiovascular risk.