Who Really Benefits from Vitamin D? VDR Genotype Points to a 19% Diabetes Risk Reduction

ApaI Genotype and Vitamin D Diabetes Benefit High-dose vitamin D has shown mixed results for preventing type 2 diabetes in people with prediabetes, raising the question of whether only certain genetic subgroups derive real benefit. This genetic association analysis of 2,098 adults with prediabetes nested within the D2d randomized trial re‑examined the effect of 4,000 IU/day vitamin D₃ versus placebo over a median 2.5‑year follow‑up, focusing on three common vitamin D receptor (VDR) polymorphisms (ApaI, BsmI, FokI) and achieved intratrial 25‑hydroxyvitamin D (25[OH]D) levels.

In a discovery phase (n = 1,903), higher intratrial 25(OH)D ( 40–49.9 and ≥50 ng/mL ) was associated with markedly lower diabetes risk in carriers of ApaI CC and AC genotypes—hazard ratios for incident diabetes fell to 0.29 and 0.17 for CC, and 0.51 and 0.26 for AC, compared with 20–29.9 ng/mL as the reference—while…