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

Am J Clin Nutr. 2019 Nov 1;110(5):1138-1147. doi: 10.1093/ajcn/nqz171.


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 D3 supplementation on insulin resistance (IR) and β-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 µg) vitamin D3 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 β-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 D3 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 β-cell function.

Conclusion: This study employed a robust assessment of IR 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.This trial was registered on clinicaltrials.gov as NCT01889810.

Keywords: euglycemic–hyperinsulinemic clamp; insulin resistance; prediabetes; vitamin D; β-cell function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholecalciferol / administration & dosage*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Insulin Resistance*
  • Insulin-Secreting Cells / physiology*
  • Male
  • Middle Aged
  • Prediabetic State / physiopathology*


  • Cholecalciferol

Associated data

  • ClinicalTrials.gov/NCT01889810