Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes
Authors' conclusion
This genetic association study of adults with prediabetes suggests that diabetes risk reduction after supplementation with 4000 IU/d of vitamin D3 was restricted to participants carrying the AC and CC alleles of the ApaI polymorphism. These findings support the potential role of ApaI genotyping in identifying individuals most likely to experience benefits from high-dose vitamin D3 treatment to reduce diabetes risk.
Study context
- Population
- Adults with prediabetes in the D2d trial with available intratrial 25(OH)D levels and genotyping; mean age 60.2 years, 55.7% men1,903 in discovery phase
- Participants
- 2,098 adults
- Comparison
- Vitamin D3 4000 IU/d vs placebo, by ApaI genotype
- Primary endpoint
- Incident diabetes with vitamin D3 vs placebo according to ApaI genotypes (test phase)
- Follow-up
- Median 2.5 years (IQR, 1.8-3.5 years)
Methodological detailssecondary analysis of the D2d randomised trial, vitamin D receptor (VDR) genotype analysis of ApaI, BsmI and FokI polymorphisms, discovery phase and test phase analyses, D2d trial conducted October 1, 2013, to November 28, 2018; analysis January 3 to November 30, 2025
- Secondary analysis of the D2d randomised trial
- VDR genotype analysis of ApaI, BsmI and FokI polymorphisms
- Discovery phase and test phase analyses
- D2d trial conducted October 1, 2013, to November 28, 2018; analysis January 3 to November 30, 2025
Primary result
As reported in the abstract
Incident diabetes by ApaI genotype
Vitamin D3 vs PlaceboHazard ratio (95% CI)
ApaI AA (n=618): no response
1.02(0.72–1.44)
ApaI AC and CC (n=1480): 19% decrease in risk
0.81(0.66–0.99)
Original publication
Vitamin D Receptor Polymorphisms and the Effect of Vitamin D Supplementation on Diabetes Risk Among Adults With Prediabetes. JAMA Netw Open. Published 1 April 2026. doi:10.
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