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

Oct 2014

DOI: 10.1371/journal.pone.0109607

Citations:139

Influential Citations:5

Interventional (Human) Studies

Enhanced Details

Methods

Six-month, double-blind, randomized, placebo-controlled trial at a single site; 95 adults at risk of type 2 diabetes (prediabetes or AUSDRISK ≥15), vitamin D deficient at baseline; mean age ~54 years; BMI ~31 kg/m^2; majority women; multi-ethnic; analyses included participants who completed baseline and final visits (treatment n=35; placebo n=45).

Intervention

Vitamin D3 2,000 IU daily with breakfast; dose escalated by 2,000 IU every 2 months to reach ≥75 nmol/L; Calcium carbonate 1,200 mg elemental calcium daily with breakfast; duration 6 months.

Results

No significant changes in OGTT-derived insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, C-peptide AUC) or beta-cell function (Matsuda index × C-peptide AUC) or in inflammatory/metabolic markers with supplementation versus placebo. In a post hoc analysis of participants with prediabetes, insulin sensitivity improved with vitamin D and calcium (HOMA%S and Matsuda index). Serum 25(OH)D rose to ~95 nmol/L in the treatment group (≈91% reached ≥75 nmol/L). Conclusion: six months of calcium plus vitamin D may not improve insulin-related measures in the general at-risk population, but may enhance insulin sensitivity in those with prediabetes; longer, targeted trials are needed.

Limitations

Underpowered due to not meeting target sample size; potential residual confounding from imbalanced randomization; 16% dropout; none had severe vitamin D deficiency at baseline; high baseline calcium intake limits generalizability; not using gold-standard insulin sensitivity measure; short duration (6 months); single-site study; applicability to populations with low calcium intake or different nutrient interactions uncertain.

Abstract

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 show less