Effect of Vitamin D3 Supplementation on Insulin Resistance and β-Cell Function in Prediabetes: A Double-Blind Randomised Placebo Controlled Trial

Abstract

Background: Observational studies have suggested an inverse association between low serum 25(OH)D concentrations and development of type 2 diabetes. High-quality trials are required to test the hypothesis that vitamin D is a direct contributor to type 2 diabetes pathogenesis. The purpose of this double-blind randomised placebo controlled trial was to investigate the effect of vitamin D3 supplementation on insulin resistance and β-cell function in people with prediabetes and suboptimal vitamin D status(<50nmol/l). Methods: Sixty-six individuals were randomised to receive 3000IU(75µg) vitamin D3 or placebo daily for 26 weeks. Compliance was monitored by pill count and change in serum 25(OH)D concentration using liquid chromatography-mass spectrometry. The primary endpoint was between-group difference in change in insulin resistance assessed using a two-step euglycaemic hyperinsulinaemic clamp combined with infusion of tritiated glucose. An oral glucose tolerance test was performed pre and post-intervention to calculate indices of β-cell function. Between group comparisons were made using analysis of covariance(ANCOVA). Findings: 64 participants completed the study. Baseline serum 25(OH)D in the vitamin D3 and placebo group was 30.7 and 30.0nmol/l with status increasing by 70.5nmol/l and 5.3nmol/l respectively(between group difference in vitamin D=65.8nmol/l(95% CI 54.2, 77.3, p<0.01),after supplementation. There was no difference between groups in measures of whole-body,peripheral or hepatic insulin resistance or in any measure of glycaemic control or β-cell function. Interpretation: This study employed a robust assessment of insulin resistance and β-cell function and targeted a high-risk population with low 25(OH)D status at baseline and found that Vitamin D3 supplementation had no effect on insulin action in people with prediabetes. Trial Registration Number: This trial was registered on clinicaltrials.gov as NCT01889810. Funding Statement: This research was funded by a N.I. HSC R&D Fellowship, NI Chest, Heart & Stroke and The Royal Victoria Hospital Belfast Metabolic Unit Research Fund. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Ethical approval for this trial was obtained from the Office for Research Ethics Committee Northern Ireland (ORECNI) (Project ID 117728).