Vitamin D supplementation has no effect on insulin sensitivity or secretion in Vitamin D-deficient, overweight or obese adults: A randomized placebo-controlled trial

Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of Vitamin D, variability in participants' Vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion. Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether Vitamin D supplementation that is provided in a sufficient dose and duration to Vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of goldstandard methods. We hypothesized that Vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo. Design: Sixty-five overweight or obese, Vitamin D-deficient (25-hydroxyVitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)]. Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m²): 30.9 ± 4.4]. 25(OH)D increased with Vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with 20.03 ± 2.8 mg • kg^-1 • min^-1, respectively; P = 0.9) or firstphase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary Vitamin D intake (P>0.1). Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in Vitamin D-deficient, overweight or obese adults, despite using high-dose Vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that Vitamin D supplementation would be an effective strategy for reducing diabetes risk even in Vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721. Am J Clin Nutr 2017;105:1372-81.