JAMA Netw Open
Could vitamin D prevent diabetes? Your patient’s genes may hold the answer
Clinical Takeaway: High-dose vitamin D supplementation (4000 IU/day) reduced progression to diabetes in patients with prediabetes who carried specific vitamin D receptor genotypes; benefits were not seen across all genetic profiles.
Prediabetes affects more than 115 million U.S. adults, yet prevention strategies remain limited. A new genetic analysis of the large D2d randomized clinical trial suggests that vitamin D supplementation may reduce diabetes risk in adults with prediabetes—but only in those with certain vitamin D receptor (VDR) gene variants.
Researchers examined data from 2,098 U.S. adults with prediabetes who were assigned to vitamin D3 (4000 IU daily) or placebo for a median of 2.5 years. While the original D2d trial showed no significant reduction in diabetes incidence overall, this secondary analysis focused on common VDR polymorphisms.
Participants with the ApaI AC or CC genotypes experienced a 19% lower risk of progressing to type 2 diabetes when taking vitamin D (hazard ratio, 0.81), compared with placebo. In contrast, those with the ApaI AA genotype—about 30% of participants—derived no measurable benefit from supplementation.
The findings help explain why prior studies of vitamin D and diabetes prevention have produced mixed results. Prior D2d analyses also showed that maintaining serum 25-hydroxyvitamin D levels of 40 to 50 ng/mL or higher was associated with progressively greater risk reductions.
“Could vitamin D still benefit some people?” asked lead author Bess Dawson-Hughes, MD, of Tufts University. “If we can delay the time period that an individual will spend living with diabetes, we can stop some of those harmful side effects or lessen their severity.”
Investigators emphasize that routine genetic testing is not yet recommended but say the results point toward a future of more personalized preventive care, where simple supplementation strategies could be matched to patients most likely to benefit.
Source: Dawson-Hughes B, et al. (2026, April 23). JAMA Netw Open. Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes