Effect of vitamin D3 supplementation on insulin resistance and β-cell function in prediabetes: a double-blind, randomized, placebo-controlled trial

Background: Observational studies have suggested an inverse association between low serum 25-hydroxyvitamin D [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. Objective: The purpose of this double-blind randomized placebo-controlled trial was to investigate the effect of vitamin D-3 supplementation on insulin resistance (IR) and beta-cell function in people with prediabetes and suboptimal vitamin D status (<50 nmol/L). Methods: Sixty-six individuals were randomly assigned to receive 3000 IU (75 mu g) vitamin D-3 or placebo daily for 26 wk. Compliance was monitored by pill count and change in serum 25(OH)D concentration using LC-MS. The primary endpoint was between-group difference in change in IR assessed using a 2-step euglycemic-hyperinsulinemic clamp combined with infusion of tritiated glucose. An oral-glucose-tolerance test was performed pre- and postintervention to calculate indices of beta-cell function. Between-group comparisons were made using ANCOVA. Results: In total, 64 participants completed the study. Baseline serum 25(OH)D concentrations in the vitamin D-3 and placebo group were 30.7 and 30.0 nmol/L, with status increasing by 70.5 nmol/L and 5.3 nmol/L, respectively (between-group difference in vitamin D: 65.8 nmol/L; 95% CI: 54.2, 77.3 nmol/L; P < 0.01), after supplementation. There was no difference between groups in measures of whole-body, peripheral, or hepatic IR or in any measure of glycemic control or beta-cell function. Conclusion: This study employed a robust assessment of IR and beta-cell function and targeted a high-risk population with low 25(OH)D status at baseline and found that vitamin D-3 supplementation had no effect on insulin action in people with prediabetes.