title: 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.
abstract: OBJECTIVE
  To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.
  
  
  METHODS
  6-month randomized, placebo-controlled trial.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ACTRN12609000043235.
authors.affiliation: Department of Medicine, NorthWest Academic Centre, The University of Melbourne, Western Health, Melbourne, Australia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gagnon
authors.affiliation: Department of Medicine, NorthWest Academic Centre, The University of Melbourne, Western Health, Melbourne, Australia.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Daly
authors.affiliation: Department of Medicine, University of Sherbrooke, Sherbrooke, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Carpentier
authors.affiliation: Melbourne Pathology, Melbourne, Australia; Department of Medicine, Monash University, Melbourne, Australia.
authors.forename: Zhong X
authors.initials: ZX
authors.lastname: Lu
authors.affiliation: Department of Medicine, NorthWest Academic Centre, The University of Melbourne, Western Health, Melbourne, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Shore-Lorenti
authors.affiliation: Melbourne Pathology, Melbourne, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Sikaris
authors.affiliation: Department of Chronic Diseases Surveillance, Institut national de santé publique du Québec, Quebec City, Canada; Department of Medicine, Laval University, Quebec City, Canada.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jean
authors.affiliation: Department of Medicine, NorthWest Academic Centre, The University of Melbourne, Western Health, Melbourne, Australia.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Ebeling
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000096:biosynthesis; D002097:C-Reactive Protein / Q000378:metabolism; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002762:Cholecalciferol / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000494:pharmacology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D010865:Pilot Projects; D011236:Prediabetic State / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D002096:C-Peptide; D002136:Calcium, Dietary; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D002762:Cholecalciferol; D002097:C-Reactive Protein