BACKGROUND Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic β cell function are limited.

OBJECTIVE We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR, and β cell function.

DESIGN We recruited 1080 nondiabetic Korean subjects [mean ± SD age: 49.5 ± 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test.

RESULTS Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (≥20 ng/mL), and the incidence of T2D at 32.3 ± 15.6 mo (±SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with ≥20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with ≥20 ng/mL.

CONCLUSION The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481.