Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial 1,2

Background: It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). Objective: We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. Design: This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged $ 65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. Results: In total, 222 subjects (55% women) with a mean 6 SD age and body mass index (BMI; in kg/m 2 ) of 71 6 4 y and 30 6 4, respectively, completed the study. Subjects’ baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean 6 SD serum 25(OH)D increased from 20 6 7 to 26 6 7 ng/mL in the low-dose arm ( P , 0.0001) and from 21 6 8 to 36 6 10 ng/mL in the high-dose arm ( P , 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high- [2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. Conclusion: Vitamin D 3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals. This trial was registered at clinicaltrials.gov as NCT01315366. J Clin

[1]  N. Suksomboon,et al.  Effect of vitamin D supplementation on insulin resistance and glycaemic control in prediabetes: a systematic review and meta‐analysis , 2016, Diabetic medicine : a journal of the British Diabetic Association.

[2]  J. Manson,et al.  Update on the Vitamin D and OmegA-3 trial (VITAL) , 2016, The Journal of Steroid Biochemistry and Molecular Biology.

[3]  E. Cagliero,et al.  Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. , 2015, The American journal of clinical nutrition.

[4]  C. Cooper,et al.  Serum 25‐Hydroxyvitamin D Levels: Variability, Knowledge Gaps, and the Concept of a Desirable Range , 2015, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  Madhukar Mittal,et al.  Effect of vitamin D supplementation on glycemic control in patients with type 2 diabetes: a systematic review of interventional studies , 2015, Journal of Diabetes & Metabolic Disorders.

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

[7]  C. Shore-Lorenti,et al.  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 , 2014, PloS one.

[8]  Jennifer G. Robinson,et al.  Calcium/vitamin D supplementation, serum 25-hydroxyvitamin D concentrations, and cholesterol profiles in the Women’s Health Initiative calcium/vitamin D randomized trial , 2014, Menopause.

[9]  Elizabeth L. Barry,et al.  Genetic variants in CYP2R1, CYP24A1, and VDR modify the efficacy of vitamin D3 supplementation for increasing serum 25-hydroxyvitamin D levels in a randomized controlled trial. , 2014, The Journal of clinical endocrinology and metabolism.

[10]  S. Majumdar,et al.  Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. , 2014, The Journal of clinical endocrinology and metabolism.

[11]  I. Njølstad,et al.  No Effect of High-Dose Vitamin D Supplementation on Glycemic Status or Cardiovascular Risk Factors in Subjects With Prediabetes , 2014, Diabetes Care.

[12]  D. Knol,et al.  Effect of moderate-dose vitamin D supplementation on insulin sensitivity in vitamin D-deficient non-Western immigrants in the Netherlands: a randomized placebo-controlled trial. , 2014, The American journal of clinical nutrition.

[13]  A. Avenell,et al.  Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. , 2014, The Cochrane database of systematic reviews.

[14]  J. Ioannidis,et al.  Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials , 2014, BMJ : British Medical Journal.

[15]  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.

[16]  Do Hoon Kim,et al.  Blood vitamin D status and metabolic syndrome in the general adult population: a dose-response meta-analysis. , 2014, The Journal of clinical endocrinology and metabolism.

[17]  Ahmad Esmaillzadeh,et al.  Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial. , 2013, The American journal of clinical nutrition.

[18]  F. Shidfar,et al.  Does vitamin D3 supplementation improve glucose homeostasis in overweight or obese women? A double‐blind, randomized, placebo‐controlled clinical trial , 2013, Diabetic medicine : a journal of the British Diabetic Association.

[19]  L. Rejnmark,et al.  Effects of vitamin D supplementation on body fat accumulation, inflammation, and metabolic risk factors in obese adults with low vitamin D levels - results from a randomized trial. , 2013, European journal of internal medicine.

[20]  S. Boonen,et al.  Optimal vitamin D status: a critical analysis on the basis of evidence-based medicine. , 2013, The Journal of clinical endocrinology and metabolism.

[21]  D. Lütjohann,et al.  Vitamin D3 effects on lipids differ in statin and non-statin-treated humans: superiority of free 25-OH D levels in detecting relationships. , 2013, The Journal of clinical endocrinology and metabolism.

[22]  R. Herr,et al.  A systematic review of vitamin D status in populations worldwide , 2013, British Journal of Nutrition.

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

[24]  D. Viswanath,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2012, Pediatrics.

[25]  O. Franco,et al.  Vitamin D, type 2 diabetes and other metabolic outcomes: a systematic review and meta-analysis of prospective studies , 2012, Proceedings of the Nutrition Society.

[26]  D. Reid,et al.  Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. , 2012, The Journal of clinical endocrinology and metabolism.

[27]  M. Witham,et al.  Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta‐analysis , 2012, Diabetic medicine : a journal of the British Diabetic Association.

[28]  Tianjing Li,et al.  Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. , 2012, The Journal of clinical endocrinology and metabolism.

[29]  Lynette M. Smith,et al.  Dose Response to Vitamin D Supplementation in Postmenopausal Women , 2012, Annals of Internal Medicine.

[30]  R. Jorde,et al.  Vitamin D, Insulin Secretion, Sensitivity, and Lipids , 2011, Diabetes.

[31]  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.

[32]  Nada Adra,et al.  Nutrition Transition and Cardiovascular Disease Risk Factors in Middle East and North Africa Countries: Reviewing the Evidence , 2010, Annals of Nutrition and Metabolism.

[33]  G. Fuleihan,et al.  Hypovitaminosis D in developing countries—prevalence, risk factors and outcomes , 2010, Nature Reviews Endocrinology.

[34]  R. Jorde,et al.  No improvement in cardiovascular risk factors in overweight and obese subjects after supplementation with vitamin D3 for 1 year , 2010, Journal of internal medicine.

[35]  T. Trikalinos,et al.  Vitamin D and Cardiometabolic Outcomes: A Systematic Review , 2010 .

[36]  J. Nagpal,et al.  A double‐blind, randomized, placebo‐controlled trial of the short‐term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle‐aged, centrally obese men , 2009, Diabetic medicine : a journal of the British Diabetic Association.

[37]  S. Ish-shalom,et al.  Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. , 2008, The Journal of clinical endocrinology and metabolism.

[38]  D. Leroith,et al.  The metabolic syndrome--from insulin resistance to obesity and diabetes. , 2008, Endocrinology and metabolism clinics of North America.

[39]  M. Holick.  Vitamin D deficiency. , 2007, The New England journal of medicine.

[40]  A. Mitrakou,et al.  The Effects of Calcium and Vitamin D Supplementation on Blood Glucose and Markers of Inflammation in Nondiabetic Adults , 2007, Diabetes Care.

[41]  G. E. El-Hajj Fuleihan,et al.  Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect? , 2006, Bone.

[42]  J. Real,et al.  Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. , 2003, Diabetes care.

[43]  R. Walker,et al.  Diagnosing insulin resistance in the general population. , 2001, Diabetes care.

[44]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[45]  K. H. Madsen,et al.  Common variants in CYP2R1 and GC genes are both determinants of serum 25-hydroxyvitamin D concentrations after UVB irradiation and after consumption of vitamin D₃-fortified bread and milk during winter in Denmark. , 2015, The American journal of clinical nutrition.

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

[47]  P. Autier,et al.  Vitamin D status and ill health: a systematic review. , 2014, The lancet. Diabetes & endocrinology.