Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial

Authors: Barbora de Courten, Aya Mousa, Negar Naderpoor, Helena Teede, Maximilian P J de Courten, Robert Scragg

Published in: Trials | Issue 1/2015

Login to get access

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/Design

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.

Discussion

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.

Trial registration

Clinicaltrials.gov ID: NCT02112721.
Literature
1.
Holick MF. Vitamin D, status: measurement, interpretation, and clinical application. Ann Epidemiol. 2009;19(2):73–8.PubMed
2.
Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y: nationwide cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007;85(3):860–8.PubMed
3.
Pittas A, Lau J, Hu F, Dawson-Hughes B. The role of Vitamin D and calcium in type 2 diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92:2017–29.PubMedPubMedCentral
4.
Grandi NC, Breitling LP, Brenner H. Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Prev Med. 2010;51(3–4):228–33.PubMed
5.
Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33(10):2238–43.PubMedPubMedCentral
6.
Sinclair C. Risks and benefits of sun exposure: implications for public health practice based on the Australian experience. Prog Biophys Mol Biol. 2006;92(1):173–8.PubMed
7.
Holick MF. Vitamin D, deficiency in 2010: health benefits of vitamin D and sunlight: a D-bate. Nat Rev Endocrinol. 2011;7(2):73–5.PubMed
8.
Government A. Department of Health and Aging, National Health and Medical Research Council. Nutrient reference values for Australia and New Zealand: executive summary. Canberra: NHMRC; 2006.
9.
Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.PubMed
10.
Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008;87(3):688–91.PubMed
11.
Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001;73(2):288–94.PubMed
12.
Need AG, O’Loughlin PD, Horowitz M, Nordin BE. Relationship between fasting serum glucose, age, body mass index and serum 25 hydroxyvitamin D in postmenopausal women. Clin Endocrinol. 2005;62(6):738–41.
13.
Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, et al. Plasma 25-hydroxyvitamin D is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr. 2009;139(2):329–34.PubMedPubMedCentral
14.
Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr. 2004;79(5):820–5.PubMed
15.
Ou HY, Karnchanasorn R, Lee LZ, Chiu KC. Interaction of BMI with vitamin D and insulin sensitivity. Eur J Clin Investig. 2011;41(11):1195–201.
16.
Hypponen E, Power C. Vitamin D status and glucose homeostasis in the 1958 British birth cohort: the role of obesity. Diabetes Care. 2006;29(10):2244–6.PubMed
17.
Pinelli NR, Jaber LA, Brown MB, Herman WH. Serum 25-hydroxy vitamin D and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care. 2010;33(6):1373–5.PubMedPubMedCentral
18.
Gannage-Yared MH, Chedid R, Khalife S, Azzi E, Zoghbi F, Halaby G. Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population. Eur J Endocrinol. 2009;160(6):965–71.PubMed
19.
Burgaz A, Byberg L, Rautiainen S, Orsini N, Hakansson N, Arnlov J, et al. Confirmed hypertension and plasma 25(OH)D concentrations amongst elderly men. J Intern Med. 2011;269(2):211–8.PubMed
20.
Jorde R, Grimnes G. Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res. 2011;50(4):303–12.PubMed
21.
Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin D is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990–2000. Diabetes. 2008;57(10):2619–25.PubMedPubMedCentral
22.
Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study). Diabetes Care. 2011;34(5):1133–8.PubMedPubMedCentral
23.
Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152(5):307–14.PubMedPubMedCentral
24.
Zittermann A. Vitamin D, and cardiovascular disease. Anticancer Res. 2014;34(9):4641–8.PubMed
25.
Zittermann A, Prokop S. The role of vitamin D for cardiovascular disease and overall mortality. Adv Exp Med Biol. 2014;810:106–19.PubMed
26.
Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, et al. Clinical review: effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99(10):3551–60.PubMedPubMedCentral
27.
Vozarova B, Weyer C, Lindsay RS, Pratley RE, Bogardus C, Tataranni PA. High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes. Diabetes. 2002;51(2):455–61.PubMed
28.
Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev. 2008;29(1):42–61.PubMed
29.
Palomer X, Gonzalez-Clemente JM, Blanco-Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10(3):185–97.PubMed
30.
Sanghi D, Mishra A, Sharma AC, Singh A, Natu SM, Agarwal S, et al. Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clin Orthop Relat Res. 2013;471(11):3556–62.PubMedPubMedCentral
31.
Shaw J, Tanama S. Diabetes: the silent pandemic and its impact on Australia. Canberra: Diabetes Australia; 2012.
32.
Kupferschmidt K. Uncertain verdict as vitamin D goes on trial. Science. 2012;337(6101):1476–8.PubMed
33.
Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr. 2011;65(9):1005–15.PubMedPubMedCentral
34.
Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003;88(1):157–61.PubMed
35.
Bischof MG, Heinze G, Vierhapper H. Vitamin D status and its relation to age and body mass index. Horm Res. 2006;66(5):211–5.PubMed
36.
Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R. The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003;57(4):258–61.PubMed
37.
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;15(7):539–53.PubMed
38.
Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95.PubMed
39.
Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev. 1988;8(1):77–100.
40.
Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85(1):6–18.PubMed
41.
Svendsen OL, Haarbo J, Hassager C, Christiansen C. Accuracy of measurements of body composition by dual-energy X-ray absorptiometry in vivo. Am J Clin Nutr. 1993;57(5):605–8.PubMed
42.
43.
Norman AW. Sunlight, season, skin pigmentation, vitamin D, and 25-hydroxyvitamin D: integral components of the vitamin D endocrine system. Am J Clin Nutr. 1998;67(6):1108–10.PubMed
44.
Rosso S, Minarro R, Schraub S, Tumino R, Franceschi S, Zanetti R. Reproduceability of skin characteristic measurements and reported sun exposure history. Int J Epidemiol. 2002;31:439–46.PubMed
45.
Barger-Lux MJ, Heaney RP. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab. 2002;87(11):4952–6.PubMed
46.
Carmody DP. Psychometric characteristics of the Beck Depression Inventory-II with college students of diverse ethnicity. Int J Psychiatry Clin Pract. 2005;9(1):22–8.PubMed
47.
Schotte CK, Maes M, Cluydts R, De Doncker D, Cosyns P. Construct validity of the Beck Depression Inventory in a depressive population. J Affect Disord. 1997;46(2):115–25.PubMed
48.
Chung HK, Cho Y, Choi S, Shin MJ. The association between serum 25-hydroxyvitamin D concentrations and depressive symptoms in Korean adults: findings from the fifth Korea National Health and Nutrition Examination Survey 2010. PLoS One. 2014;9(6):e99185.PubMedPubMedCentral
49.
Howland RH. Vitamin D, and depression. J Psychosoc Nurs Ment Health Serv. 2011;49(2):15–8.PubMed
50.
Siegert RJ, Tennant A, Turner-Stokes L. Rasch analysis of the Beck Depression Inventory-II in a neurological rehabilitation sample. Disabil Rehabil. 2010;32(1):8–17.PubMed
51.
Al-Jarallah K, Shehab D, Abraham M, Mojiminiyi OA, Abdella NA. Musculoskeletal pain: should physicians test for vitamin D level? Int J Rheum Dis. 2013;16(2):193–7.PubMed
52.
Cranney A, Horsley T, O’Donnell S, Weiler H, Puil L, Ooi D, et al. Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess. 2007;158:1–235.
53.
Hamman RF, Horton E, Barrett-Connor E, Bray GA, Christophi C, Crandall J, et al. Factors affecting the decline in incidence of diabetes in the Diabetes Prevention Program Outcome Study (DPPOS). Diabetes. 2015;64:989–98.PubMed
54.
von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient: a randomised, placebo-controlled trial. Br J Nutr. 2010;103(4):549–55.
55.
Dunlop TW, Vaisanen S, Frank C, Molnar F, Sinkkonen L, Carlberg C. The human peroxisome proliferator-activated receptor δ gene is a primary target of 1α,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol. 2005;349(2):248–60.PubMed
56.
Maestro B, Campion J, Davila N, Calle C. Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J. 2000;47(4):383–91.PubMed
57.
Maestro B, Molero S, Bajo S, Davila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D3. Cell Biochem Funct. 2002;20(3):227–32.PubMed
58.
Cavalier E, Delanaye P, Souberbielle JC, Radermecker RP. Vitamin D and type 2 diabetes mellitus: where do we stand? Diabetes Metab. 2011;37(4):265–72.PubMed
59.
Dutta D, Mondal SA, Choudhuri S, Maisnam I, Hasanoor Reza AH, Bhattacharya B, et al. Vitamin-D supplementation in prediabetes reduced progression to type 2 diabetes and was associated with decreased insulin resistance and systemic inflammation: an open label randomized prospective study from Eastern India. Diabetes Res Clin Pract. 2014;103:e18–23.PubMed
60.
Pratley RE, Weyer C. Progression from IGT to type 2 diabetes mellitus: the central role of impaired early insulin secretion. Curr Diab Rep. 2002;2(3):242–8.PubMed
61.
Mark AB, Poulsen MW, Andersen S, Andersen JM, Bak MJ, Ritz C, et al. Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women. Diabetes Care. 2014;37(1):88–95.PubMed
62.
Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys. 2000;374(2):334–8.PubMed
63.
Baz-Hecht M, Goldfine AB. The impact of vitamin D deficiency on diabetes and cardiovascular risk. Curr Opin Endocrinol Diabetes Obes. 2010;17(2):113–9.PubMed
64.
Farmer JA. Renin angiotensin system and ASCVD. Curr Opin Cardiol. 2000;15(3):141–50.PubMed
65.
Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243–8.PubMed
66.
Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr. 2014;100(3):746–55.PubMed
67.
Vaidya A, Forman JP. Vitamin D and vascular disease: the current and future status of vitamin D therapy in hypertension and kidney disease. Curr Hypertens Rep. 2012;14(2):111–9.PubMedPubMedCentral
68.
Sourris KC, Lyons JG, Dougherty SL, Chand V, Straznicky NE, Schlaich MP, et al. Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure. Clin Chem Lab Med. 2014;52(1):129–38.PubMed
69.
Al-Daghri NM, Alkharfy KM, Al-Saleh Y, Al-Attas OS, Alokail MS, Al-Othman A, et al. Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study. Metab Clin Exp. 2012;61(5):661–6.PubMed
70.
Carbone LD, Rosenberg EW, Tolley EA, Holick MF, Hughes TA, Watsky MA, et al. 25-Hydroxyvitamin D, cholesterol, and ultraviolet irradiation. Metab Clin Exp. 2008;57(6):741–8.PubMed
71.
Wehmeier KR, Mazza A, Hachem S, Ligaray K, Mooradian AD, Wong NC, et al. Differential regulation of apolipoprotein A-I gene expression by vitamin D receptor modulators. Biochim Biophys Acta. 2008;1780(2):264–73.PubMed
72.
Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Mathieu C. Vitamin D and diabetes: its importance for beta cell and immune function. Mol Cell Endocrinol. 2011;347(1–2):106–20.PubMed
73.
Giulietti A, van Etten E, Overbergh L, Stoffels K, Bouillon R, Mathieu C. Monocytes from type 2 diabetic patients have a pro-inflammatory profile. 1,25-dihydroxyvitamin D3 works as anti-inflammatory. Diabetes Res Clin Pract. 2007;77(1):47–57.PubMed
74.
Deb DK, Chen Y, Zhang Z, Zhang Y, Szeto FL, Wong KE, et al. 1,25-dihydroxyvitamin D3 suppresses high glucose-induced angiotensinogen expression in kidney cells by blocking the NF-κB pathway. Am J Physiol Renal Physiol. 2009;296(5):F1212–8.PubMedPubMedCentral
75.
Harant H, Andrew PJ, Reddy GS, Foglar E, Lindley IJ. 1α,25-dihydroxyvitamin D3 and a variety of its natural metabolites transcriptionally repress nuclear-factor-κB-mediated interleukin-8 gene expression. Eur J Biochem. 1997;250(1):63–71.PubMed
76.
Szeto FL, Sun J, Kong J, Duan Y, Liao A, Madara JL, et al. Involvement of the vitamin D receptor in the regulation of NF-κB activity in fibroblasts. J Steroid Biochem Mol Biol. 2007;103(3–5):563–6.PubMed
77.
Podsakoff PM, MacKenzie SB, Lee JY, Podsakoff NP. Common method biases in behavioral research: a critical review of the literature and recommended remedies. J Appl Psychol. 2003;88(5):879–903.PubMed
Metadata
Title
Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial
Authors
Barbora de Courten
Aya Mousa
Negar Naderpoor
Helena Teede
Maximilian P J de Courten
Robert Scragg
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0851-6

Other articles of this Issue 1/2015

Trials 1/2015 Go to the issue

Study protocol

Pilot study to evaluate a tailored text message intervention for pregnant smokers (MiQuit): study protocol for a randomised controlled trial

Study protocol

Vertebroplasty for acute painful osteoporotic fractures (VAPOUR): study protocol for a randomized controlled trial

Study protocol

Kava for the treatment of generalised anxiety disorder (K-GAD): study protocol for a randomised controlled trial

Study protocol

Harmonizing Optimal Strategy for Treatment of coronary artery diseases – comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS RCT): study protocol for a randomized controlled trial

Study protocol

Supported self-management for adults with type 2 diabetes and a learning disability (OK-Diabetes): study protocol for a randomised controlled feasibility trial

Study protocol

Lactose-free milk for infants with acute gastroenteritis in a developing country: study protocol for a randomized controlled trial