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

Abstract

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 β 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 (Hb A(1c)) of 5.9%. There was no significant vitamin D × 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). Hb A(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 β cell function and had a marginal effect on attenuating the rise in Hb A(1c). This trial was registered at clinicaltrials.gov as NCT00436475.

FIGURE 1.

Flow of participants. Data on the primary outcome (the disposition index) were not available for 4 participants either because the frequently sampled intravenous-glucose-tolerance test was not done at baseline and follow-up (n = 1) or the test was stopped prematurely because of symptomatic hypoglycemia and the disposition index could not be estimated (n = 3). These 4 participants were excluded from the analysis of the primary outcome (the disposition index) and insulin sensitivity index, but they all contributed data to secondary outcomes (insulin secretion and measures of glycemia). Data from participants who withdrew or who were lost to follow-up were included in the analysis by carrying over their baseline values.

FIGURE 2.

Mean (±SEM) changes in the disposition index between baseline and week 16. All data are least squares means adjusted for stratified variables (age and BMI), the baseline value of the outcome variable, race, and time of study entry. A: Changes in the disposition index between vitamin D (300 ± 130) and no vitamin D (−126 ± 127) or between calcium (79 ± 130) and no calcium (83 ± 135). P values are for the ANOVA test for differences in means between vitamin D and no vitamin D or between calcium and no calcium. B: Changes in the disposition index for vitamin D and calcium (286 ± 169) compared with vitamin D alone (315 ± 181) compared with calcium alone (−122 ± 176) compared with placebo (−128 ± 173). P values are for the ANOVA test for differences in means compared with placebo. P = 0.92 for the vitamin D × calcium interaction.