Vitamin D, insulin secretion, sensitivity, and lipids: results from a case-control study and a randomized controlled trial using hyperglycemic clamp technique

Diabetes. 2011 Nov;60(11):2748-57. doi: 10.2337/db11-0650. Epub 2011 Sep 12.


Objective: Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.

Research design and methods: Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.

Results: The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.

Conclusions: Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile.

Trial registration: NCT00809744.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Calcifediol / blood
  • Capsules
  • Carbohydrate Metabolism, Inborn Errors / etiology
  • Carbohydrate Metabolism, Inborn Errors / prevention & control
  • Case-Control Studies
  • Cholecalciferol / therapeutic use*
  • Dietary Supplements*
  • Female
  • Glucose Clamp Technique
  • Glycated Hemoglobin / analysis
  • Glycerol Kinase / deficiency
  • Humans
  • Hyperglycemia / etiology
  • Hyperglycemia / prevention & control
  • Hypoadrenocorticism, Familial
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Resistance*
  • Insulin Secretion
  • Lipids / blood*
  • Male
  • Middle Aged
  • Triglycerides / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / prevention & control*


  • Capsules
  • Glycated Hemoglobin A
  • Insulin
  • Lipids
  • Triglycerides
  • hemoglobin A1c protein, human
  • Cholecalciferol
  • Glycerol Kinase
  • Calcifediol

Associated data