Folic acid: a marker of endothelial function in type 2 diabetes?
OBJECTIVE
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 intra-brachial infusion of the endothelial-dependent vasodilator acetylcholine (15 microg/min) and the endothelial-independent vasodilator sodium nitroprusside (2 microg/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, R2 = 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.
Mangoni
Arduino A
AA
Department of Clinical Pharmacology, Centre for Neuroscience, School of Medicine, Flinders University, Adelaide, SA, Australia. arduino.mangoni@flinders.edu.au
Sherwood
Roy A
RA
Asonganyi
Belinda
B
Ouldred
Emma L
EL
Thomas
Stephen
S
Jackson
Stephen H D
SH
D000109:Acetylcholine; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009599:Nitroprusside; D012044:Regression Analysis; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D015415:Biomarkers; D014665:Vasodilator Agents; D009599:Nitroprusside; D005492:Folic Acid; D000109:Acetylcholine