Vitamin D Supplementation for Prevention of Type 2 Diabetes Mellitus: To D or Not to D?

Abstract Context Over the last decade, vitamin D has emerged as a risk determinant for type 2 diabetes and vitamin D supplementation has been hypothesized as a potential intervention to lower diabetes risk. Recently, several trials have reported on the effect of vitamin D supplementation on diabetes prevention in people with prediabetes. Evidence Acquisition A comprehensive literature review was performed using PubMed, Embase, and ClinicalTrials.gov to identify: (1) recent meta-analyses of longitudinal observational studies that report on the association between blood 25-hydroxyvitamin D (25[OH]D) level and incident diabetes, and (2) clinical trials of adults with prediabetes that have reported on the effect of vitamin D supplementation on incident diabetes. Evidence Synthesis Longitudinal observational studies report highly consistent associations between higher blood 25(OH)D levels and a lower risk of incident diabetes in diverse populations, including populations with prediabetes. Trials in persons with prediabetes show risk reduction in incident diabetes with vitamin D supplementation. In the 3 large trials that were specifically designed and conducted for the prevention of diabetes, vitamin D supplementation, when compared with placebo, reduced the risk of developing diabetes by 10% to 13% in persons with prediabetes not selected for vitamin D deficiency. Conclusions Results from recent trials are congruent with a large body of evidence from observational studies indicating that vitamin D has a role in modulating diabetes risk. Participant-level meta-analysis of the 3 largest trials should provide a more refined estimate of risk reduction and identify patient populations that are likely to benefit the most from vitamin D supplementation.

[1]  L. Lunsford,et al.  Effects of Vitamin D Supplementation on Prevention of Type 2 Diabetes in Patients With Prediabetes: A Systematic Review and Meta-analysis , 2020, Diabetes Care.

[2]  J. Manson,et al.  Effect of Vitamin D Supplementation on the Incidence of Diabetes Mellitus. , 2020, The Journal of clinical endocrinology and metabolism.

[3]  J. Peto,et al.  High-dose oral vitamin D supplementation and mortality in people aged 65-84 years: the VIDAL cluster feasibility RCT of open versus double-blind individual randomisation. , 2020, Health technology assessment.

[4]  S. Saydah,et al.  Prevalence of Diabetes by Race and Ethnicity in the United States, 2011-2016. , 2019, JAMA.

[5]  W. Knowler,et al.  Pharmacologic Randomized Clinical Trials in Prevention of Type 2 Diabetes , 2019, Current Diabetes Reports.

[6]  P. McKeigue,et al.  Phenome-wide Mendelian-randomization study of genetically determined vitamin D on multiple health outcomes using the UK Biobank study , 2019, International journal of epidemiology.

[7]  A. Marette,et al.  Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomized, placebo-controlled trial. , 2019, European journal of endocrinology.

[8]  J. Ware,et al.  Vitamin D Supplementation and Prevention of Type 2 Diabetes. , 2019, The New England journal of medicine.

[9]  S. Greenland,et al.  Scientists rise up against statistical significance , 2019, Nature.

[10]  M. Niroomand,et al.  Does high-dose vitamin D supplementation impact insulin resistance and risk of development of diabetes in patients with pre-diabetes? A double-blind randomized clinical trial. , 2019, Diabetes research and clinical practice.

[11]  T. Kawahara Eldecalcitol, a Vitamin D Analog, for Diabetes Prevention in Impaired Glucose Tolerance (DPVD Study) , 2018, Diabetes.

[12]  M. McCarthy,et al.  Association of vitamin D with risk of type 2 diabetes: A Mendelian randomisation study in European and Chinese adults , 2018, PLoS medicine.

[13]  W. Willett,et al.  The Misuse of Meta-analysis in Nutrition Research. , 2017, JAMA.

[14]  B. Boucher,et al.  Why vitamin D clinical trials should be based on 25-hydroxyvitamin D concentrations , 2017, The Journal of Steroid Biochemistry and Molecular Biology.

[15]  V. Gudnason,et al.  Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data , 2017, PloS one.

[16]  C. Sempos,et al.  Trends in Use of High-Dose Vitamin D Supplements Exceeding 1000 or 4000 International Units Daily, 1999-2014 , 2017, JAMA.

[17]  K. Birkeland,et al.  Effects of Vitamin D Supplementation on Insulin Sensitivity and Insulin Secretion in Subjects With Type 2 Diabetes and Vitamin D Deficiency: A Randomized Controlled Trial , 2017, Diabetes Care.

[18]  Stuart J Pocock,et al.  The Primary Outcome Fails - What Next? , 2016, The New England journal of medicine.

[19]  Yoshiya Tanaka,et al.  Rationale and design of Diabetes Prevention with active Vitamin D (DPVD): a randomised, double-blind, placebo-controlled study , 2016, BMJ Open.

[20]  J. Robins,et al.  The Potential for Postrandomization Confounding in Randomized Clinical Trials. , 2016, JAMA.

[21]  D. English,et al.  The D-Health Trial: A randomized trial of vitamin D for prevention of mortality and cancer. , 2016, Contemporary clinical trials.

[22]  J. Cauley,et al.  Associations of total and free 25OHD and 1,25(OH)2D with serum markers of inflammation in older men , 2016, Osteoporosis International.

[23]  I. Njølstad,et al.  Vitamin D 20,000 IU per Week for Five Years Does Not Prevent Progression From Prediabetes to Diabetes. , 2016, The Journal of clinical endocrinology and metabolism.

[24]  E. Barengolts,et al.  EFFECT OF HIGH-DOSE VITAMIN D REPLETION ON GLYCEMIC CONTROL IN AFRICAN-AMERICAN MALES WITH PREDIABETES AND HYPOVITAMINOSIS D. , 2015, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[25]  B. Laway,et al.  Effect of Vitamin D supplementation on glycemic parameters and progression of prediabetes to diabetes: A 1-year, open-label randomized study , 2015, Indian journal of endocrinology and metabolism.

[26]  H. Rasmussen,et al.  Dietary fat increases vitamin D-3 absorption. , 2015, Journal of the Academy of Nutrition and Dietetics.

[27]  S. Sharp,et al.  Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study , 2015, The lancet. Diabetes & endocrinology.

[28]  J. Ware,et al.  Rationale and Design of the Vitamin D and Type 2 Diabetes (D2d) Study: A Diabetes Prevention Trial , 2014, Diabetes Care.

[29]  S. Bojesen,et al.  Vitamin D concentration, obesity, and risk of diabetes: a mendelian randomisation study. , 2014, The lancet. Diabetes & endocrinology.

[30]  S. Mukhopadhyay,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. , 2014, Diabetes research and clinical practice.

[31]  James M Robins,et al.  Randomized Trials Analyzed as Observational Studies , 2013, Annals of Internal Medicine.

[32]  C. Wagner,et al.  Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: Why clinical dose intervals can affect clinical outcomes. , 2013, The Journal of clinical endocrinology and metabolism.

[33]  M. Schulze,et al.  Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study , 2013, European Journal of Epidemiology.

[34]  J. Manson,et al.  Blood 25-Hydroxy Vitamin D Levels and Incident Type 2 Diabetes , 2013, Diabetes Care.

[35]  S. Bojesen,et al.  Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. , 2013, Clinical chemistry.

[36]  P. Ebeling,et al.  Is High Dose Vitamin D Harmful? , 2013, Calcified Tissue International.

[37]  Martin L. Lee,et al.  High-Dose Vitamin D Supplementation in People With Prediabetes and Hypovitaminosis D , 2013, Diabetes Care.

[38]  R. Heaney,et al.  Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity , 2012, Obesity.

[39]  Tom Wilsgaard,et al.  Polymorphisms Related to the Serum 25-Hydroxyvitamin D Level and Risk of Myocardial Infarction, Diabetes, Cancer and Mortality. The Tromsø Study , 2012, PloS one.

[40]  F. Hu,et al.  Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes , 2012, Diabetes Care.

[41]  F. Hu,et al.  Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. , 2011, The American journal of clinical nutrition.

[42]  M. Morris,et al.  A potential design flaw of randomized trials of vitamin supplements. , 2011, JAMA.

[43]  A. Avenell,et al.  Vitamin D supplementation and type 2 diabetes: a substudy of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). , 2009, Age and ageing.

[44]  C. Mathieu,et al.  Vitamin D and human health: lessons from vitamin D receptor null mice. , 2008, Endocrine reviews.

[45]  Stephen W Lagakos,et al.  Statistics in medicine--reporting of subgroup analyses in clinical trials. , 2007, The New England journal of medicine.

[46]  Bess Dawson-Hughes,et al.  The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. , 2007, The Journal of clinical endocrinology and metabolism.

[47]  H. DeLuca Overview of general physiologic features and functions of vitamin D. , 2004, The American journal of clinical nutrition.

[48]  M. Hewison,et al.  Expression of 25-hydroxyvitamin D3-1α-hydroxylase in pancreatic islets , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[49]  M. Saad,et al.  Hypovitaminosis D is associated with insulin resistance and β cell dysfunction , 2004 .

[50]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002, The New England journal of medicine.

[51]  B. Billaudel,et al.  Vitamin D and pancreatic islet function I. Time course for changes in insulin secretion and content during vitamin D deprivation and repletion , 1988, Journal of endocrinological investigation.

[52]  M. Holick,et al.  Aging decreases the capacity of human skin to produce vitamin D3. , 1985, The Journal of clinical investigation.

[53]  A. B. Hill The Environment and Disease: Association or Causation? , 1965, Proceedings of the Royal Society of Medicine.

[54]  J. Manson,et al.  The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. , 2012, Contemporary clinical trials.

[55]  Anastassios,et al.  Plasma 25-Hydroxyvitamin D and Progression to Diabetes in Patients at Risk for Diabetes An ancillary analysis in the Diabetes Prevention Program , 2012 .

[56]  B. Kestenbaum,et al.  Calcium plus vitamin D supplementation and the risk of incident diabetes mellitus in the Women ’ s Health Initiative , 2008 .

[57]  Ben Renow-Clarke,et al.  The Statistics Report , 2004 .