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]; I2 = 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]) (Pinteraction = 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]; I2 = 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.
Focusing on the major RCT in this analysis, the negative D2d, its accompanying editorial said in the NEJM, "The observed hazard ratio of 0.88 does not rule out a modest benefit... In contrast, in the Diabetes Prevention Program, the risk ...was lower by 58% with a lifestyle intervention...". Also in the D2d, post hoc benefit was found in the "small group of participants with a baseline serum 25-hydroxyvitamin D level of less than 12 ng per milliliter".