Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial

Background: A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking. Objective: We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes. Design: Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic beta cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia. Results: Participants had a mean age of 57 y, a body mass index (BMI; in kg/m(2)) of 32, and glycated hemoglobin (HbA(1c)) of 5.9%. There was no significant vitamin D x calcium interaction on any outcomes. The disposition index increased in the vitamin D group and decreased in the no-vitamin D group (adjusted mean change +/- SE: 300 +/- 130 compared with -126 +/- 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 +/- 39 compared with -36 +/- 37 mU.L-1.min, respectively; P = 0.046). HbA(1c) increased less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group (0.06 +/- 0.03% compared with 0.14 +/- 0.03%, respectively; P = 0.081). There was no significant difference in any outcomes with calcium compared with no calcium. Conclusion: In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol improved beta cell function and had a marginal effect on attenuating the rise in HbA(1c). This trial was registered at clinicaltrials.gov as NCT00436475. Am J Clin Nutr 2011;94:486-94.