A recent review compiled three trials that tested cholecalciferol or eldecalcitol against matching placebos in 4,190 participants with prediabetes and a mean body mass index (BMI) of at least 30 kg/m2. The primary outcome of new-onset diabetes occurred in 22.7% of those taking vitamin D versus 25.0% of those on placebo, for an unadjusted hazard ratio of 0.88 and an adjusted hazard ratio of 0.85 with vitamin D supplementation.
The review was published by Annals of Internal Medicine online Feb. 7 and in the March print issue and summarized in the February ACP Diabetes Monthly. The following commentary by Darren Lau, MD, PhD, was published in the ACP Journal Club section of Annals of Internal Medicine on May 2.
Vitamin D affects insulin secretion and sensitivity. The systematic review and meta-analysis by Pittas and colleagues show that vitamin D lowers the risk for diabetes. The dose–response finding that higher achieved 25-hydroxyvitamin D levels were associated with better treatment-related reductions in diabetes increases the credibility of the findings.
The review found that adults with obesity had less response to cholecalciferol, but a comparable benefit for those with and without obesity was seen in the single trial (DPVD study) that used an activated vitamin D metabolite, eldecalcitol. The authors suggest that higher doses of cholecalciferol or the use of activated metabolites may be needed for adults with obesity. Activated metabolites come with their own challenges, including increased cost and, possibly, hypercalcemia. Given the small number of studies and low statistical power in the included DPVD trial, conclusions regarding activated metabolites for adults with obesity remain speculative.
The benefit of vitamin D, with a 13% relative risk reduction and number needed to treat (NNT) of 31, applies to the adults with prediabetes enrolled in the included trials, who tended to be those with the highest risk for progression. Absolute benefit will be lower if applied to unselected adults with prediabetes in the real world. The benefit of vitamin D is smaller than seen with other interventions, such as the intensive lifestyle intervention (NNT = 7) and metformin (NNT = 14) in the Diabetes Prevention Program. The downstream microvascular and macrovascular benefits we can expect from vitamin D are unclear but not more so than for any other diabetes prevention intervention.
Although vitamin D at doses of 3200 to 4000 IU has been associated with hypercalcemia and falls, it does not appear to increase the risk for kidney stones, and the risk for vitamin D–associated hypercalcemia is <1%.
Supplementation of ≤4000 IU daily is widely considered safe and costs mere cents. Although other preventive treatments may be more effective, vitamin D has comparative advantages of convenience, tolerability, availability, and lower cost. For adults with high-risk prediabetes (i.e., multiple biomarkers indicating prediabetes, additional risk factors for progression, or risk factors for vitamin D deficiency), vitamin D (cholecalciferol) at a dose of ≤4000 IU/d offers an additional preventive option.