Teaching Topic 

Vitamin D and Prevention of Type 2 Diabetes 

ORIGINAL ARTICLE

Vitamin D Supplementation and Prevention of Type 2 Diabetes

A.G. Pittas and Others

  

Over the past decade, a low blood 25-hydroxyvitamin D level has emerged as a possible risk factor for type 2 diabetes, and vitamin D supplementation has been proposed as a potential intervention to lower diabetes risk. Pittas et al. conducted a double-blind, placebo-controlled trial which evaluated whether vitamin D supplementation, regardless of the baseline serum 25-hydroxyvitamin D level, reduced the risk of new-onset type 2 diabetes among adults at high risk for diabetes.

Clinical Pearls

  Why would vitamin D status influence the risk of type 2 diabetes?

The hypothesis that vitamin D status may influence the risk of type 2 diabetes is biologically plausible, because both impaired pancreatic beta-cell function and insulin resistance have been reported with low blood 25-hydroxyvitamin D levels. Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of diabetes. In short-term mechanistic studies, vitamin D supplementation improved the disposition index, a measure of pancreatic beta-cell function, by 40%.

  How much vitamin D supplementation was used in the trial by Pittas et al.?

Participants were randomly assigned to take a single, once-daily soft-gel pill containing either 4000 IU of vitamin D₃ or matching placebo. The vitamin D dose of 4000 IU per day is the recommended upper intake level to avert potential toxicity, although data from large trials on the safety on this dose have been scant. There is concern that 25-hydroxyvitamin D levels above 50 ng per milliliter (125 nmol per liter) may be associated with adverse effects.

Morning Report Questions

Q. Does vitamin D supplementation decrease the risk of new-onset type 2 diabetes among adults at high risk of diabetes?

A. In the trial by Pittas et al., vitamin D₃ supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo after a median follow-up of 2.5 years. New-onset diabetes (the primary outcome) occurred in 293 participants (273 cases diagnosed by trial-specific laboratory testing and 20 diagnosed by adjudication) in the vitamin D group and 323 patients (305 cases diagnosed by trial-specific laboratory testing and 18 diagnosed by adjudication) in the placebo group (9.39 events and 10.66 events per 100 person-years, respectively). The hazard ratio in the vitamin D group was 0.88 (95% confidence interval [CI], 0.75 to 1.04; P=0.12).

Q. What influenced the decision to exclude serum 25-hydroxyvitamin D level as an eligibility criterion in the trial by Pittas et al.?

A. Owing to ethical and practical considerations, a lack of consensus on the preferred 25-hydroxyvitamin D level, and the desire to maximize the external validity of the trial, the authors specifically did not include serum 25-hydroxyvitamin D as an eligibility criterion. Because vitamin D supplements are used increasingly in the U.S. adult population, approximately 8 of 10 participants had a baseline serum 25-hydroxyvitamin D level that was considered to be sufficient according to current recommendations (≥20 ng per milliliter) to reduce the risk of many outcomes, including diabetes. The high percentage of participants with adequate levels of vitamin D may have limited the ability of the trial to detect a significant effect.