Mini-review. Vitamin D for the prevention of type 2 diabetes: Evidence and implications.

Prediabetes is common worldwide and offers a critical opportunity for interventions to prevent type 2 diabetes. Vitamin D has biologically plausible effects on beta cell function, insulin sensitivity, and the immune system, and observational studies consistently associate higher 25-hydroxyvitamin D (25[OH]D) levels with a lower risk of developing diabetes. Three randomized, double-blind, placebo-controlled trials designed specifically for adults with prediabetes tested moderate-to-high doses of vitamin D3 (Tromsø, D2d) or an active analog (DPVD). Each study showed a modest reduction in progression to type 2 diabetes. An individual participant data meta-analysis of these trials (n = 4190) demonstrated a 15% relative risk reduction, with greater benefit among those with low baseline 25(OH)D levels or a body mass index less than 30 kg/m2. Vitamin D supplementation also increased the likelihood of regression to normal glucose regulation. These findings are further supported by multiple aggregate-data meta-analyses showing a consistent benefit of vitamin D supplementation in adults with prediabetes. Compared with intensive lifestyle interventions, metformin, and incretin-based therapies, vitamin D is inexpensive, safe, accessible, and easy to implement, with an estimated number needed to treat of ∼30. The 2024 Endocrine Society Guideline now recommends vitamin D supplementation for adults with prediabetes at doses above the recommended dietary allowance without requiring routine 25(OH)D testing. Achieving and maintaining a blood 25(OH)D level above 40 ng/mL may confer additional benefit, but the hypothesis needs to be tested in clinical trials.