Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency - a double-blind, randomized, placebo-controlled trial

Metabolism. 2014 Sep;63(9):1115-24. doi: 10.1016/j.metabol.2014.06.008. Epub 2014 Jun 19.


Objectives: Vitamin D insufficiency is common in subjects with type 2 diabetes. Observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes. However, results of intervention studies have been inconsistent. We investigated the effects of improving vitamin D status on insulin sensitivity, insulin secretion, and inflammatory markers in patients with type 2 diabetes.

Materials/methods: A double blind, randomized, placebo controlled trial was conducted. Sixteen patients with type 2 diabetes and hypovitaminosis D were recruited. Eight patients received colecalciferol and (280 μg daily for 2 weeks, 140 μg daily for 10 weeks) and 8 patients received identical placebo tablets for 12 weeks. Before and after intervention, patients underwent IVGTT, hyperinsulinemic euglycemic clamp, assessment of baseline high-frequency insulin pulsatility, glucose-entrained insulin pulsatility, DXA scans, 24-hour-ambulatory blood pressure monitorings, and fasting blood samples.

Results: Serum-25(OH) vitamin D and serum-1,25(OH)₂ vitamin D increased significantly after 12 weeks in the intervention group (p=0.01, p=0.004). Serum-25(OH) vitamin D was also significantly higher in the vitamin D group compared to the placebo group (p=0.02) after intervention. Although no significant changes in insulin sensitivity, inflammation, blood pressure, lipid profile, or HbA1c were found, we observed borderline (p between 0.05 and 0.10) improvements of insulin secretion, in terms of c-peptide levels, first phase incremental AUC insulin and insulin secretory burst mass.

Conclusions: Improvement in vitamin D status does not improve insulin resistance, blood pressure, inflammation or HbA1c, but might increase insulin secretion in patients with established type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT00812578.

Keywords: Hyperinsulinemic euglycemic clamp; Inflammation; Insulin pulsatility; Vitamin D deficiency.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Peptide / blood
  • Calcifediol / blood
  • Calcitriol / blood
  • Cholecalciferol / administration & dosage*
  • Cholecalciferol / metabolism
  • Cholecalciferol / therapeutic use
  • Denmark
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / immunology
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Inflammation Mediators / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism*
  • Kinetics
  • Male
  • Middle Aged
  • Seasons
  • Severity of Illness Index
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / diet therapy*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology


  • Biomarkers
  • C-Peptide
  • Inflammation Mediators
  • Insulin
  • Cholecalciferol
  • Calcitriol
  • Calcifediol

Associated data

  • ClinicalTrials.gov/NCT00812578