Effect of Vitamin D3 Supplementation on Improving Glucose Homeostasis and Preventing Diabetes: A Systematic Review and Meta-Analysis

Context: Observational studies report consistent associations between low vitamin D concentration and increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are mixed. Objective: The objective of the study was to systematically review RCTs that report on the effects of vitamin D supplementation on glucose homeostasis or diabetes prevention. Data Sources: Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013. Study Selection: Study selection was trials that compared vitamin D-3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes. Data Extraction and Synthesis: Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences (MDs) and odds ratios. The main outcomes of interest were homeostasis model assessment of insulin resistance, homeostasis model assessment of beta-cell function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and adverse events. Data Synthesis: Thirty-five trials (43 407 patients) with variable risk of bias were included. Vitamin D had no significant effects on insulin resistance [homeostasis model assessment of insulin resistance: MD -0.04; 95% confidence interval (CI) -0.30 to 0.22, I-squared statistic (I-2) = 45%], insulin secretion (homeostasis model of beta-cell function: MD 1.64; 95% CI -25.94 to 29.22, I-2 = 40%), or hemoglobin A1c (MD -0.05%; 95% CI -0.12 to 0.03, I-2 = 55%) compared with controls. Four RCTs reported on the progression to new diabetes and found no effect of vitamin D(odds ratio 1.02; 95% CI 0.94 to 1.10, I-2 = 0%). Adverse events were rare, and there was no evidence of publication bias. Conclusions: Evidence from available trials shows no effect of vitamin D-3 supplementation on glucose homeostasis or diabetes prevention. Definitive conclusions may be limited in the context of the moderate degree of heterogeneity, variable risk of bias, and short-term follow-up duration of the available evidence to date.