8564 Vitamin D Supplementation And Incident Type 2 Diabetes In The Vitamin D And Omega-3 Trial

Abstract Disclosure: D.K. Tobias: None. A. Pradhan: None. E. Duran: None. C. Li: None. Y. Song: None. J. Buring: None. N. Cook: None. S. Mora: None. J.E. Manson: None. Background: Observational and experimental evidence suggest a role for vitamin D in the prevention of type 2 diabetes (T2D). However, prior randomized trials in high-risk populations of vitamin D supplementation for T2D are inconclusive and efficacy in the general population is unknown. Objective: To evaluate whether vitamin D supplementation reduces risk of T2D in a general population of older US adults. Design: The Vitamin D and Omega-3 Trial (VITAL) is a completed five-year randomized, double-blind, placebo-controlled 2x2 supplementation trial of vitamin D3 (cholecalciferol; 2000 IU per day) and omega-3 fatty acids (1 g per day) for the primary prevention of cancer and cardiovascular disease. VITAL-T2D, a pre-specified ancillary study initiated prior to trial enrollment, tested the efficacy of vitamin D supplementation on incident T2D risk. We also conducted a pre-registered systematic review and random effects meta-analysis of vitamin D trials (≥1000 IU/d cholecalciferol) reporting effects on T2D risk. Participants: We analyzed 22,220 VITAL participants without T2D at baseline in 2011-2014. Mean age and body mass index (BMI) were 67.2 years (SD=7.1) and 27.5 kg/m2 (SD=5.3), respectively, with 51% female and 17% African American. In addition, we analyzed change in glycemic traits at 2 years in a subcohort of 918 participants attending in-person clinic visits. Results: The cumulative incidence of T2D at median follow-up of 5.3 years was 3.98 cases/1000 PY among the vitamin D group and 4.37 cases/1000 person years (PY) for placebo (intention-to-treat hazard ratio [HR]=0.91 [0.76, 1.09]). Results were not significantly modified by age, sex, race, BMI, or baseline 25-hydroxyvitamin D levels. In a meta-analysis of three eligible randomized trials (N=25,154 participants), the relative risk (RR) for T2D with vitamin D vs. placebo was 0.89 (0.80, 1.00); p=0.049. In a meta-analysis the RR was 0.75 (0.60, 0.94) among participants with BMI <30 kg/ m2 at baseline, but was 0.99 (0.84, 1.17 among those with obesity (BMI≥30.0 kg/m2) (p-interaction=0.19). There were minimal effects of vitamin D vs. placebo on glycemic traits in the clinic subcohort overall. In analyses stratifying by baseline BMI, we observed increased HOMA-β and insulin response during oral glucose challenge at 2y for BMI<30 kg/m2 with vitamin D vs. placebo, but no benefit for participants with obesity. We did not observe effect modification by other variables. Conclusions: Vitamin D supplementation of 2000 IU/d did not significantly reduce T2D risk in a general population of US adults, but the updated meta-analysis supports potential benefits among adults without obesity. Trial and Systematic Review Registration:ClinicalTrials.gov NCT01169259 and NCT01633177; PROSPERO: CRD42019147562. Presentation: 6/1/2024