Vitamin D Supplementation and Prevention of Type 2 Diabetes.

The New England journal of medicine

Jun 2019

DOI: 10.1056/NEJMoa1900906

Citations:525

Influential Citations:32

Interventional (Human) Studies

COI

Enhanced Details

Methods

Multicenter randomized, double-blind, placebo-controlled trial in adults at high risk for type 2 diabetes with prediabetes by ADA criteria (mean age 60.0 years; BMI 32.1; 44.8% female; baseline 25-hydroxyvitamin D ~28 ng/mL).

Intervention

Vitamin D3 (cholecalciferol), 4000 IU daily, taken orally as a soft-gel capsule, for a median follow-up of 2.5 years.

Results

Vitamin D supplementation did not significantly reduce the risk of new-onset diabetes compared with placebo over a median 2.5-year follow-up (293/1211 vs 323/1212 events; hazard ratio 0.88; 95% CI 0.75–1.04; P = 0.12). Adverse events were similar between groups. Conclusion: In adults at high risk for type 2 diabetes not selected for vitamin D deficiency, 4000 IU/day vitamin D did not meaningfully prevent diabetes.

Limitations

Participants largely had adequate baseline vitamin D (mean 25-hydroxyvitamin D ~28 ng/mL), which may limit detection of benefit in deficient individuals. Not powered to detect smaller risk reductions; population was older and overweight, potentially limiting generalizability. Adherence and use of outside-of-trial vitamin D varied by group; potential residual confounding. Trial did not assess long-term safety beyond the study period.

Abstract

BACKGROUND Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (0.95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.). show less