MANAGEMENT OF ENDOCRINE DISEASE: The effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE Epidemiologic studies suggest that vitamin D status plays a role in glycaemic control in patients with type 2 diabetes. However, intervention studies yielded inconsistent results. The aim of this study is to systematically review the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. METHODS Systematic review and meta-analysis. We searched Medline, Embase and the Cochrane Library for RCTs examining the effect of vitamin D supplementation on glycaemic control in patients with type 2 diabetes. A random-effects model meta-analysis was performed to obtain a summarized outcome of vitamin D supplementation on HbA1c, fasting glucose and homeostasis model assessment - insulin resistance (HOMA-IR). RESULTS Twenty-three RCTs were included in this systematic review representing a total of 1797 patients with type 2 diabetes. Mean (± s.d.) change in serum 25-hydroxyvitamin D varied from 1.8 ± 10.2 nmol/L to 80.1 ± 54.0 nmol/L. Nineteen studies included HbA1c as outcome variable. Combining these studies no significant effect in change of HbA1c was seen after vitamin D intervention compared with placebo. A significant effect of vitamin D supplementation was seen on fasting glucose in a subgroup of studies (n = 4) with a mean baseline HbA1c ≥ 8% (64 mmol/mol) (standardized difference in means: 0.36; 95% CI: 0.12-0.61, P = 0.003). CONCLUSIONS Current evidence of RCTs does not support short-term vitamin D supplementation in a heterogeneous population with type 2 diabetes. However, in patients with poorly controlled diabetes, a favourable effect of vitamin D is seen on fasting glucose.

[1]  Shaghayegh Haghjooy Javanmard,et al.  Effects of vitamin D-fortified low fat yogurt on glycemic status, anthropometric indexes, inflammation, and bone turnover in diabetic postmenopausal women: A randomised controlled clinical trial. , 2016, Clinical nutrition.

[2]  Chong Shen,et al.  Vitamin D Receptor Genetic Polymorphism Is Significantly Associated with Risk of Type 2 Diabetes Mellitus in Chinese Han Population. , 2015, Archives of medical research.

[3]  S. Simsek,et al.  Response to Comment on Krul-Poel et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care 2015;38:1420–1426 , 2015, Diabetes Care.

[4]  P. Lips,et al.  Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial , 2015, Diabetes Care.

[5]  C. Mathieu.  Vitamin D and diabetes: Where do we stand? , 2015, Diabetes research and clinical practice.

[6]  F. Bandeira,et al.  The effects of intermittent vitamin D3 supplementation on muscle strength and metabolic parameters in postmenopausal women with type 2 diabetes: a randomized controlled study , 2015, Therapeutic advances in endocrinology and metabolism.

[7]  S. Rahman,et al.  A 3-month oral vitamin D supplementation marginally improves diastolic blood pressure in Saudi patients with type 2 diabetes mellitus. , 2014, International journal of clinical and experimental medicine.

[8]  L. Harrison,et al.  A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes. , 2014, Diabetes research and clinical practice.

[9]  A. Sadiya,et al.  Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial , 2014, European Journal of Clinical Nutrition.

[10]  Yuqian Li,et al.  Association of the vitamin D binding protein polymorphisms with the risk of type 2 diabetes mellitus: a meta-analysis , 2014, BMJ Open.

[11]  S. Ghavamzadeh,et al.  The Effect of Vitamin D Supplementation on Adiposity, Blood Glycated Hemoglobin, Serum Leptin and Tumor Necrosis Factor-α in Type 2 Diabetic Patients , 2014, International journal of preventive medicine.

[12]  L. Rejnmark,et al.  Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency - a double-blind, randomized, placebo-controlled trial. , 2014, Metabolism: clinical and experimental.

[13]  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.

[14]  Ahmad Esmaillzadeh,et al.  Effects of calcium–vitamin D co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial , 2014, Diabetologia.

[15]  Ross M. Fraser,et al.  Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study , 2014, The lancet. Diabetes & endocrinology.

[16]  S. Salekzamani,et al.  Daily intake of vitamin D- or calcium-vitamin D-fortified Persian yogurt drink (doogh) attenuates diabetes-induced oxidative stress: evidence for antioxidative properties of vitamin D. , 2014, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[17]  C. Stettler,et al.  Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study. , 2014, Swiss medical weekly.

[18]  M. Boaz,et al.  Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. , 2013, Clinical nutrition.

[19]  A. Ahmadi,et al.  Efficacy of supplementary vitamin D on improvement of glycemic parameters in patients with type 2 diabetes mellitus; a randomized double blind clinical trial , 2013, Journal of renal injury prevention.

[20]  K. Badenhoop,et al.  Effect of a Randomised Controlled Vitamin D Trial on Insulin Resistance and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus , 2013, Hormone and Metabolic Research.

[21]  F. Inserra,et al.  The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system. , 2013, American journal of physiology. Cell physiology.

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

[23]  B. Cheung,et al.  Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes. , 2013, Atherosclerosis.

[24]  R. Heshmat,et al.  Effect of vitamin D on insulin resistance and anthropometric parameters in Type 2 diabetes; a randomized double-blind clinical trial , 2012, DARU Journal of Pharmaceutical Sciences.

[25]  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.

[26]  JoAnn E Manson,et al.  The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. , 2012, Endocrine reviews.

[27]  M. Hewison.  An update on vitamin D and human immunity , 2012, Clinical endocrinology.

[28]  Mate M. Soric,et al.  Effect of daily vitamin D supplementation on HbA1c in patients with uncontrolled type 2 diabetes mellitus: A pilot study * , 2012, Journal of diabetes.

[29]  M. Rogero,et al.  Focus on Vitamin D, Inflammation and Type 2 Diabetes , 2012, Nutrients.

[30]  S. Shab-Bidar,et al.  Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial , 2011, BMC medicine.

[31]  J. Mitri,et al.  Vitamin D and type 2 diabetes: a systematic review , 2011, European Journal of Clinical Nutrition.

[32]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[33]  JoAnn E. Manson,et al.  The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know , 2010, The Journal of clinical endocrinology and metabolism.

[34]  I. Njølstad,et al.  Baseline serum 25‐hydroxyvitamin D concentrations in the Tromsø Study 1994–95 and risk of developing type 2 diabetes mellitus during 11 years of follow‐up , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[35]  A. Morris,et al.  The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial , 2010, Diabetologia.

[36]  H. Parving,et al.  Vitamin D Levels and Mortality in Type 2 Diabetes , 2010, Diabetes Care.

[37]  N. Shah,et al.  Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus. , 2010, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[38]  R. Jorde,et al.  Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels , 2009, European journal of nutrition.

[39]  J. Sugden,et al.  Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[40]  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.

[41]  M. Hewison,et al.  Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. , 2004, The Journal of steroid biochemistry and molecular biology.

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

[43]  E. Barrett-Connor,et al.  Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo Study. , 2002, Metabolism: clinical and experimental.

[44]  D. Altman,et al.  Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice , 2002, Journal of health services research & policy.

[45]  G. Smith,et al.  Bias in meta-analysis detected by a simple, graphical test , 1997, BMJ.

[46]  O. Ryu,et al.  A prospective randomized controlled trial of the effects of vitamin D supplementation on long-term glycemic control in type 2 diabetes mellitus of Korea. , 2014, Endocrine journal.

[47]  Graham D Carter,et al.  Accuracy of 25-hydroxyvitamin D assays: confronting the issues. , 2011, Current drug targets.

[48]  J. Sugden,et al.  The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial , 2010, Diabetologia.

[49]  P M Stewart,et al.  Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. , 2001, The Journal of clinical endocrinology and metabolism.