Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus.
BACKGROUND
Endothelial dysfunction, a precursor of vascular disease, begins early in type 1 diabetes mellitus and is associated with folate status.


METHODS
A randomized, double-blind, placebo-controlled study of folate (5 mg daily) and vitamin B6 (100 mg daily) in 124 children with type 1 diabetes determined the immediate and 8-week effects of these vitamins, alone and in combination, on endothelial function. Endothelial function, assessed as flow-mediated dilation and glyceryltrinitrate-induced dilation with high-resolution ultrasound of the brachial artery, was measured at baseline, at 2 and 4 hours after the first dose (n = 35), and at 4 and 8 weeks of treatment (n = 122).


RESULTS
Flow-mediated dilation normalized in all treatment groups. From baseline to 8 weeks, flow-mediated dilation improved with folate from 2.6% +/- 4.3% (mean +/- SD) to 9.7% +/- 6.0%, with vitamin B6 from 3.5% +/- 4.0% to 8.3% +/- 4.2%, and with folate/vitamin B6 from 2.8% +/- 3.5% to 10.5% +/- 4.4%. This improvement in flow-mediated dilation occurred within 2 hours and was maintained at 8 weeks for each treatment. Flow-mediated dilation in the placebo group, and glyceryltrinitrate-induced dilation in all groups, did not change. Increases in serum folate, red cell folate, and serum vitamin B6 levels related to increases in flow-mediated dilation. Improvement in flow-mediated dilation was independent of changes in total plasma homocyst(e)ine, glucose, hemoglobin A1c, and high-sensitivity C-reactive protein levels. Baseline red cell folate levels and baseline diastolic blood pressure were related inversely to improvement in flow-mediated dilation. Serum triglyceride and low-density lipoprotein cholesterol inversely related to baseline flow-mediated dilation.


CONCLUSIONS
High-dose folate and vitamin B6 normalized endothelial dysfunction in children with type 1 diabetes. This effect was maintained over 8 weeks, with no additional benefit from combination treatment.
MacKenzie
Karen E
KE
Department of Diabetes and Endocrinology, Children, Youth, and Women's Health Service, Adelaide, Australia. karen.mackenzie@adelaide.edu.au
Wiltshire
Esko J
EJ
Gent
Roger
R
Hirte
Craig
C
Piotto
Lino
L
Couper
Jennifer J
JJ
D000293:Adolescent; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006397:Hematinics / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D012039:Regional Blood Flow; D012107:Research Design; D014463:Ultrasonography; D025101:Vitamin B 6 / Q000008:administration & dosage / Q000494:pharmacology*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000494:pharmacology*
D006397:Hematinics; D014803:Vitamin B Complex; D025101:Vitamin B 6; D005492:Folic Acid