Published online July 3, 2006
PEDIATRICS Vol. 118 No. 1 July 2006, pp. 242-253 (doi:10.1542/peds.2005-2143)
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Folate and Vitamin B6 Rapidly Normalize Endothelial Dysfunction In Children With Type 1 Diabetes Mellitus

Karen E. MacKenzie, MBChB, FRACPa,b, Esko J. Wiltshire, MD, FRACPc, Roger Gent, DMUd, Craig Hirte, BSc(Hons)e, Lino Piotto, DMUd and Jennifer J. Couper, MD, FRACPa,b

a Department of Diabetes and Endocrinology
d Department of Paediatric Ultrasonography
e Public Health Research Unit, Children, Youth, and Women's Health Service, Adelaide, Australia
b Department of Paediatrics, University of Adelaide, Adelaide, Australia
c Department of Paediatrics, Wellington School of Medicine and Health Sciences, Wellington, New Zealand

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.

Key Words: type 1 diabetes • endothelial function • folate • pyridoxine • randomized • controlled trial

Abbreviations: FMD—flow-mediated dilation • HbA1c—hemoglobin A1c • Hs-CRP—high-sensitivity C-reactive protein • LDL—low-density lipoprotein • HDL—high-density lipoprotein • RCF—red blood cell folate • WCH—Women's and Children's Hospital

Accepted Feb 15, 2006.




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