Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial

PLoS One. 2014 Oct 9;9(10):e109607. doi: 10.1371/journal.pone.0109607. eCollection 2014.


Objectives: To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.

Design: 6-month randomized, placebo-controlled trial.

Participants: Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45).

Intervention: Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000-6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months.

Measurements: Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin.

Results: Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed.

Conclusions: Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000043235.

Publication types

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

MeSH terms

  • Adiponectin / metabolism
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • C-Peptide / biosynthesis
  • C-Reactive Protein / metabolism
  • Calcium, Dietary / administration & dosage*
  • Cholecalciferol / administration & dosage*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Dietary Supplements*
  • Female
  • Humans
  • Insulin / biosynthesis
  • Insulin / pharmacology
  • Insulin Resistance
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Osteocalcin / metabolism
  • Pilot Projects
  • Prediabetic State / diet therapy*
  • Prediabetic State / metabolism
  • Prediabetic State / physiopathology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin D Deficiency / diet therapy*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology


  • ADIPOQ protein, human
  • Adiponectin
  • Blood Glucose
  • C-Peptide
  • Calcium, Dietary
  • IL6 protein, human
  • Insulin
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Osteocalcin
  • Cholecalciferol
  • C-Reactive Protein

Associated data

  • ANZCTR/ACTRN12609000043235

Grants and funding

This study was supported by a grant from the Diabetes Australia Research Trust, no grant number assigned, http://www.diabetesaustralia.com.au/Research/DART/; PRE, RMD, CG. This study was also supported by funds from the Department of Medicine, The University of Melbourne, Australia. No grant number assigned or URL; PRE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.