Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis

BACKGROUND While observational studies have shown an association between vitamin D insufficiency and diabetes, it is unclear whether intervention with vitamin D supplements can lower the risk of type 2 diabetes mellitus (T2DM). PURPOSE To assess whether vitamin D supplementation reduces the risk of T2DM in people with prediabetes. DATA SOURCES We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 5 July 2019. STUDY SELECTION We included randomized controlled trials assessing vitamin D supplementation versus placebo in relation to new-onset T2DM in people with prediabetes. DATA EXTRACTION We screened studies and extracted data from published trials independently. DATA SYNTHESIS We identified eight eligible trials with a total of 4,896 subjects. Vitamin D supplementation significantly reduced the risk of T2DM (risk ratio [RR] 0.89 [95% CI 0.80-0.99];I-2= 0%). Benefit was found in nonobese subjects (RR 0.73 [95% CI 0.57-0.92]) but not in obese subjects (RR 0.95 [95% CI 0.84-1.08]) (P-interaction= 0.048). The reversion of prediabetes to normoglycemia occurred in 116 of 548 (21.2%) participants in the vitamin D group and 75 of 532 (14.1%) in the control group. Vitamin D supplementation increased reversion rate of prediabetes to normoglycemia (RR 1.48 [95% CI 1.14-1.92];I-2= 0%.) LIMITATIONS Definitions of prediabetes and new-onset diabetes in eligible studies were different, and long-term data on outcomes of T2DM prevention were lacking. CONCLUSIONS In persons with prediabetes, vitamin D supplementation reduces the risk of T2DM and increases the reversion rate of prediabetes to normoglycemia. The benefit of the prevention of T2DM could be limited to nonobese subjects. Individual participant data meta-analyses are needed to confirm these findings.