title: Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Despite Australia's sunny climate, low vitamin D levels are increasingly prevalent. Sun exposure is limited by long working hours, an increase in time spent indoors, and sun protection practices, and there is limited dietary vitamin D fortification. While the importance of vitamin D for bone mineralization is well known, its role as a protective agent against chronic diseases, such as type 2 diabetes and cardiovascular disease, is less understood. Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion, mainly via its anti-inflammatory properties, thereby decreasing the risk of development and progression of type 2 diabetes. The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D (25(OH)D), obtained through vitamin D supplementation, will increase insulin sensitivity and insulin secretion. A secondary aim is to determine whether these relationships are mediated by a reduction in underlying subclinical inflammation associated with obesity.
  
  
  METHODS
  Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old, with low vitamin D levels (25(OH)D < 50 nmol/l), will be randomly assigned to intervention or placebo. At baseline, participants will undergo a medical review and anthropometric measurements, including dual X-ray absorptiometry, an intravenous glucose tolerance test, muscle and fat biopsies, a hyperinsulinemic euglycemic clamp, and questionnaires assessing diet, physical activity, sun exposure, back and knee pain, and depression. The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D (cholecalciferol) daily, while the placebo group will receive apparently identical capsules, both for a period of 16 weeks. All measurements will be repeated at follow-up, with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group. Secondary outcome measures will compare changes in anthropometry, cardiovascular risk factors, and inflammatory markers.
  
  
  CONCLUSIONS
  The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms, which are relevant for the prevention and management of type 2 diabetes.
  
  
  BACKGROUND
  Clinicaltrials.gov ID: NCT02112721 .
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC, 3186, Australia. barbora.decourten@monash.edu.|Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Australia. barbora.decourten@monash.edu.
authors.forename: Barbora
authors.initials: B
authors.lastname: de Courten
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC, 3186, Australia. aya.mousa@monash.edu.
authors.forename: Aya
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC, 3186, Australia. negar.naderpoor@monash.edu.|Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Australia. negar.naderpoor@monash.edu.
authors.forename: Negar
authors.initials: N
authors.lastname: Naderpoor
authors.affiliation: Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, VIC, 3186, Australia. helena.teede@monash.edu.|Diabetes and Vascular Medicine Unit, Monash Health, Melbourne, Australia. helena.teede@monash.edu.
authors.forename: Helena
authors.initials: H
authors.lastname: Teede
authors.affiliation: Centre for Chronic Disease, Victoria University, Melbourne, Australia. Maximilian.deCourten@vu.edu.au.
authors.forename: Maximilian P J
authors.initials: MP
authors.lastname: de Courten
authors.affiliation: School of Population Health, University of Auckland, Auckland, New Zealand. r.scragg@auckland.ac.nz.
authors.forename: Robert
authors.initials: R
authors.lastname: Scragg
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002762:Cholecalciferol / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014739:Victoria; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007328:Insulin; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D