No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial

Diabetes Care. 2016 Mar;39(3):345-52. doi: 10.2337/dc15-1057. Epub 2016 Jan 19.


Objective: There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes.

Research design and methods: Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0-12 min) and second-phase (12-120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control.

Results: A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43-82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results.

Conclusions: This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.

Trial registration: NCT01497132.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / pharmacology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucose Intolerance / drug therapy
  • Glucose Tolerance Test
  • Glycated Hemoglobin
  • Homeostasis / drug effects
  • Humans
  • Insulin Resistance*
  • Insulin-Secreting Cells / drug effects*
  • Male
  • Middle Aged
  • Prediabetic State / blood
  • Prediabetic State / drug therapy*
  • Vitamins / administration & dosage*
  • Vitamins / pharmacology


  • Blood Glucose
  • Glycated Hemoglobin A
  • Vitamins
  • Cholecalciferol

Associated data