Effects of Vitamin D Supplementation on Glycaemic Control, Insulin Resistance and β Cell Function in Type 2 Diabetes Mellitus: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LIFei ¹ , HUBo ² , LIUJing-fang ¹ , ZHALong-xiao ¹ ,  ZHUXiu-li ¹

1. Department of Nursing, Medical College of Qingdao University, Qingdao 266021, China;
2. Qingdao Municipal Hospital, Qingdao 266000, China;

Corresponding author：

ZHUXiu-li, Email: 15820022927@163.com

Keywords：

Type 2 diabetes mellitus; Vitamin D; Systematic review; Meta-analysis; Randomized controlled trials

DOI：

10.7507/1672-2531.20160165

Video：

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Objective To systematically evaluate the effects of vitamin D supplementation on fasting blood glucose, insulin resistance, β cell function in type 2 diabetes mellitus. Methods Databases including PubMed, The Cochrane Library (Issue 12, 2015), Web of Science, ScienceDirect Online, VIP, CNKI, WanFang Data, and CBM were searched to collect randomized controlled trials (RCTs) about vitamin D supplementation for type 2 diabetes mellitus from inception to December 2015. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was conducted by RevMan 5.3 and Stata12.0 softwares. Results A total of 22 RCTs involving 1 756 patients were included. The results of meta-analysis showed that, compared with the control group, the vitamin D supplementation group had a significant improvement in insulin resistance (SMD=–0.68, 95%CI –1.23 to –0.12, P=0.02), but there were no significant differences in levels of FPG, HbA1c and HOMA-β between the two groups (all P value > 0.05). Subgroup analysis showed that, the levels of FPG and HOMA-IR were significantly decreased in the vitamin D supplementation group in Middle Easterners and patients whose follow-up duration was less than three months. Conclusion Vitamin D supplementation could improve HOMA-IR but could not improve the levels of FPG, HbA1c and HOMA-β. However, the evidence is weak to recommend vitamin D as a means of improving glycemic control, insulin resistance and β cell function in type 2 diabetes mellitus. Further larger, high quality trials are warranted.

Citation： LIFei, HUBo, LIUJing-fang, ZHALong-xiao, ZHUXiu-li. Effects of Vitamin D Supplementation on Glycaemic Control, Insulin Resistance and β Cell Function in Type 2 Diabetes Mellitus: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(9): 1080-1089. doi: 10.7507/1672-2531.20160165 Copy

1.	Sandu MM, Protasiewicz DC, Firănescu AG, et al. Data regarding the prevalence and incidence of diabetes mellitus and prediabetes. Rom J Diabetes Nutr Metab Dis, 2016, 23(1): 95-103.
2.	González EL, Johansson S, Wallander MA, et al. Trends in the prevalence and incidence of diabetes in the UK: 1996-2005. J Epidemiol Community Health, 2009, 63(4): 332-336.
3.	Stumvoll M, Goldstein BJ, Haeften TWV, et al. Type 2 diabetes: principles of pathogenesis and therapy. Lancet, 2005, 365(9467): 1333-1346.
4.	Chiu KC, Chu A, Go VLW, et al. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr, 2004, 79(5): 820-825.
5.	Mattila C, Knekt P, Männistö S, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care, 2007, 30(10): 2569-2570.
6.	Pittas AG, Dawson-Hughes B, Sheehan PR, et al. Rationale and design of the vitamin D type 2 diabetes (D2d) study: a diabetes prevention trial. Diabetes Care, 2014, 37(12): 3227-3234.
7.	Tahrani AA, Ball A, Shepherd L, et al. The prevalence of vitamin D abnormalities in South Asians with the type 2diabetes mellitus in the UK. Int J Clin Pract, 2010, 64(3): 351-355.
8.	Hirani V, Cumming RG, Le Couteur DG, et al. Low levels of 25-hydroxyvitamin D and active 1, 25-dihydroxyvitamin D independently associated with type 2 diabetes mellitus in older Australian men:The concord health and aging in men project. J Am Geriatr Soc, 2014, 62(9): 1741-1747.
9.	Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B, et al. The association between vitamin D status and type 2 diabetes in Thai population, a cross-sectional study. Clin Endocrinol, 2012, 77(5): 658-664.
10.	Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes, a systematic review. Eur J Clin Nutr, 2011, 65(9): 1005-1015.
11.	Song Y, Wang L, Pittas AG, et al. Blood 25-hydroxyvitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care, 2013, 36(5): 1422-1428.
12.	Marques-Vidal P, Vollenweider P, Guessous I, et al. Serum vitamin D concentrations are not associated with insulin resistance in Swiss adults. J Nutr, 2015, 145(9): 2117-2122.
13.	American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2014, 37(Suppl): S81-S90.
14.	Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 1992, 45(7): 769-773.
15.	Breslavsky A, Frand J, Matas Z, et al. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr, 2013, 32(6): 970-975.
16.	Ryu OH, Chung W, Lee S, et al. The effect of high-dose vitamin D supplementation on insulin resistance and arterialstiffness in patients with type 2 diabetes. Korean J Intern Med, 2014, 29(5): 620-629.
17.	Baziar N, Jafarian K, Shadman Z, et al. Effect of Therapeutic Dose of Vitamin D on Serum adiponectin and glycemia in vitamin D-insufficient or deficient type 2 diabetic patients. Iran Red Crescent Med J, 2014, 16(9): e21458.
18.	Kampmann U, Mosekilde L, Juhl C, 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. Metabolism, 2014, 63(9): 1115-1124.
19.	Ryu OH, Lee S, Yu J, 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. Endocr J, 2014, 61(2): 167-176.
20.	Yousefi Rad E, Djalali M, Koohdani F, et al. The effects of vitamin D supplementation on glucose control and insulin resistance in patients with diabetes type 2: a randomized clinical trial study. Iranian J Publ Health, 2014, 43(12): 1651-1656.
21.	Krul-Poel YH, Westra S, ten Boekel E, 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(8): 1420-1426.
22.	Sadiya A, Ahmed SM, Carlsson M, et al. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial. Eur J Clin Nutr, 2015, 69(6): 707-711.
23.	Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, et al. Effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trial. Daru, 2012, 20(1): 10-15.
24.	Tabesh M, Azadbakht L, Faghihimani E, et al. Effects of calcium-vitamin co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial. Diabetologia, 2014, 57(10): 2038-2047.
25.	Sugden JA, Davies JI, Witham MD, et al. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med, 2008, 25(3): 320-325.
26.	Jafari T, Faghihimani E, Feizi A, 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. Clin Nutr, 2016, 35(1): 67-76.
27.	Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr, 2009, 48(6): 349-354.
28.	Eftekhari MH, Akbarzadeh M, Dabbaghmanesh MH, et al. Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. Asia Pac J Clin Nutr, 2011, 20 (4): 521-526.
29.	Witham MD, Dove FG, Dryburgh M, et al. The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomized controlled trial. Diabetologia, 2010, 53(10): 2112-2119.
30.	Shab-Bidar S, Neyestani TR, 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. BMC Med, 2011, 9(47): 125-134.
31.	周洁, 陈海燕, 王哲, 等.补充维生素D对2型糖尿病患者胰岛素抵抗的影响.中华医学杂志, 2014, 94(43): 3407-3410.
32.	Nikooyeh B, Neyestani TR, Farvid M, et al. Daily consumption of vitamin D-or vitamin D +calcium-fortified yogurt drink improve glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr, 2011, 93(4): 764-771.
33.	Al-Zahrani MK, Elnasieh AM, Almansour FM, et al. A 3-month oral vitamin D supplementation marginally improves diastolic blood pressure in Saudi patients with type 2 diabetes mellitus. Int J Clin Exp Med, 2014, 7(12): 5421-5428.
34.	Nigil Haroon N, Anton A, John J, et al. Effect of vitamin D supplementation on glycemic control in patient with type 2 diabetes: a systematic review of interventional studies. J Diabetes Metab Disord, 2015, 14(1): 1-11.
35.	Mauss D, Jarczok MN, Hoffmann K, et al. Association of vitamin D levels with type 2 diabetes in older working adults. Int J Med Sci, 2015, 12(5): 362-368.
36.	Aloia JF, Patel M, Dimaano R, et al. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr, 2008, 87(6): 1952-1958.
37.	Reis JP, Michos ED, Selvin E, et al. Race, vitamin D–binding protein gene polymorphisms, 25-hydroxyvitamin D, and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr, 2015, 101(6): 1232-1240.
38.	Moore CE, Radcliffe JD, Liu Y, et al. Vitamin D intakes of adults differ by income, gender and race/ethnicity in the USA, 2007 to 2010. Public Health Nutr, 2014, 17(4): 756-763.
39.	Stadlmayr A, Aigner E, Huber-Schönauer U, et al. Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians. Acta Diabetol, 2015, 52(1):39-46.
40.	Parik SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1, 25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab, 2004, 89(3): 1196-1199.
41.	Wortsman J, Matsucka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr, 2000, 72(3): 690-693.
42.	王芳田, 冬梅, 童平, 等.老年2型糖尿病患者血清25羟维生素D与能量代谢关系的研究.中国糖尿病杂志, 2013, 21(8): 709-712.
43.	Liu S, Song Y, Ford ES, et al. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. Women. Diabetes Care, 2005, 28(12): 2926-2932.
44.	Reinbothe TM, Alkayyali S, Ahlqvist E, et al. The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes. Diabetologia, 2013, 56(2): 340-349.

1. Sandu MM, Protasiewicz DC, Firănescu AG, et al. Data regarding the prevalence and incidence of diabetes mellitus and prediabetes. Rom J Diabetes Nutr Metab Dis, 2016, 23(1): 95-103.
2. González EL, Johansson S, Wallander MA, et al. Trends in the prevalence and incidence of diabetes in the UK: 1996-2005. J Epidemiol Community Health, 2009, 63(4): 332-336.
3. Stumvoll M, Goldstein BJ, Haeften TWV, et al. Type 2 diabetes: principles of pathogenesis and therapy. Lancet, 2005, 365(9467): 1333-1346.
4. Chiu KC, Chu A, Go VLW, et al. Hypovitaminosis D is associated with insulin resistance and β cell dysfunction. Am J Clin Nutr, 2004, 79(5): 820-825.
5. Mattila C, Knekt P, Männistö S, et al. Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care, 2007, 30(10): 2569-2570.
6. Pittas AG, Dawson-Hughes B, Sheehan PR, et al. Rationale and design of the vitamin D type 2 diabetes (D2d) study: a diabetes prevention trial. Diabetes Care, 2014, 37(12): 3227-3234.
7. Tahrani AA, Ball A, Shepherd L, et al. The prevalence of vitamin D abnormalities in South Asians with the type 2diabetes mellitus in the UK. Int J Clin Pract, 2010, 64(3): 351-355.
8. Hirani V, Cumming RG, Le Couteur DG, et al. Low levels of 25-hydroxyvitamin D and active 1, 25-dihydroxyvitamin D independently associated with type 2 diabetes mellitus in older Australian men:The concord health and aging in men project. J Am Geriatr Soc, 2014, 62(9): 1741-1747.
9. Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B, et al. The association between vitamin D status and type 2 diabetes in Thai population, a cross-sectional study. Clin Endocrinol, 2012, 77(5): 658-664.
10. Mitri J, Muraru MD, Pittas AG. Vitamin D and type 2 diabetes, a systematic review. Eur J Clin Nutr, 2011, 65(9): 1005-1015.
11. Song Y, Wang L, Pittas AG, et al. Blood 25-hydroxyvitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care, 2013, 36(5): 1422-1428.
12. Marques-Vidal P, Vollenweider P, Guessous I, et al. Serum vitamin D concentrations are not associated with insulin resistance in Swiss adults. J Nutr, 2015, 145(9): 2117-2122.
13. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2014, 37(Suppl): S81-S90.
14. Follmann D, Elliott P, Suh I, et al. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol, 1992, 45(7): 769-773.
15. Breslavsky A, Frand J, Matas Z, et al. Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients. Clin Nutr, 2013, 32(6): 970-975.
16. Ryu OH, Chung W, Lee S, et al. The effect of high-dose vitamin D supplementation on insulin resistance and arterialstiffness in patients with type 2 diabetes. Korean J Intern Med, 2014, 29(5): 620-629.
17. Baziar N, Jafarian K, Shadman Z, et al. Effect of Therapeutic Dose of Vitamin D on Serum adiponectin and glycemia in vitamin D-insufficient or deficient type 2 diabetic patients. Iran Red Crescent Med J, 2014, 16(9): e21458.
18. Kampmann U, Mosekilde L, Juhl C, 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. Metabolism, 2014, 63(9): 1115-1124.
19. Ryu OH, Lee S, Yu J, 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. Endocr J, 2014, 61(2): 167-176.
20. Yousefi Rad E, Djalali M, Koohdani F, et al. The effects of vitamin D supplementation on glucose control and insulin resistance in patients with diabetes type 2: a randomized clinical trial study. Iranian J Publ Health, 2014, 43(12): 1651-1656.
21. Krul-Poel YH, Westra S, ten Boekel E, 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(8): 1420-1426.
22. Sadiya A, Ahmed SM, Carlsson M, et al. Vitamin D supplementation in obese type 2 diabetes subjects in Ajman, UAE: a randomized controlled double-blinded clinical trial. Eur J Clin Nutr, 2015, 69(6): 707-711.
23. Heshmat R, Tabatabaei-Malazy O, Abbaszadeh-Ahranjani S, et al. Effect of vitamin D on insulin resistance and anthropometric parameters in type 2 diabetes; a randomized double-blind clinical trial. Daru, 2012, 20(1): 10-15.
24. Tabesh M, Azadbakht L, Faghihimani E, et al. Effects of calcium-vitamin co-supplementation on metabolic profiles in vitamin D insufficient people with type 2 diabetes: a randomised controlled clinical trial. Diabetologia, 2014, 57(10): 2038-2047.
25. Sugden JA, Davies JI, Witham MD, et al. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels. Diabet Med, 2008, 25(3): 320-325.
26. Jafari T, Faghihimani E, Feizi A, 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. Clin Nutr, 2016, 35(1): 67-76.
27. Jorde R, Figenschau Y. Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels. Eur J Nutr, 2009, 48(6): 349-354.
28. Eftekhari MH, Akbarzadeh M, Dabbaghmanesh MH, et al. Impact of treatment with oral calcitriol on glucose indices in type 2 diabetes mellitus patients. Asia Pac J Clin Nutr, 2011, 20 (4): 521-526.
29. Witham MD, Dove FG, Dryburgh M, et al. The effect of different doses of vitamin D3 on markers of vascular health in patients with type 2 diabetes: a randomized controlled trial. Diabetologia, 2010, 53(10): 2112-2119.
30. Shab-Bidar S, Neyestani TR, 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. BMC Med, 2011, 9(47): 125-134.
31. 周洁, 陈海燕, 王哲, 等.补充维生素D对2型糖尿病患者胰岛素抵抗的影响.中华医学杂志, 2014, 94(43): 3407-3410.
32. Nikooyeh B, Neyestani TR, Farvid M, et al. Daily consumption of vitamin D-or vitamin D +calcium-fortified yogurt drink improve glycemic control in patients with type 2 diabetes: a randomized clinical trial. Am J Clin Nutr, 2011, 93(4): 764-771.
33. Al-Zahrani MK, Elnasieh AM, Almansour FM, et al. A 3-month oral vitamin D supplementation marginally improves diastolic blood pressure in Saudi patients with type 2 diabetes mellitus. Int J Clin Exp Med, 2014, 7(12): 5421-5428.
34. Nigil Haroon N, Anton A, John J, et al. Effect of vitamin D supplementation on glycemic control in patient with type 2 diabetes: a systematic review of interventional studies. J Diabetes Metab Disord, 2015, 14(1): 1-11.
35. Mauss D, Jarczok MN, Hoffmann K, et al. Association of vitamin D levels with type 2 diabetes in older working adults. Int J Med Sci, 2015, 12(5): 362-368.
36. Aloia JF, Patel M, Dimaano R, et al. Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr, 2008, 87(6): 1952-1958.
37. Reis JP, Michos ED, Selvin E, et al. Race, vitamin D–binding protein gene polymorphisms, 25-hydroxyvitamin D, and incident diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Am J Clin Nutr, 2015, 101(6): 1232-1240.
38. Moore CE, Radcliffe JD, Liu Y, et al. Vitamin D intakes of adults differ by income, gender and race/ethnicity in the USA, 2007 to 2010. Public Health Nutr, 2014, 17(4): 756-763.
39. Stadlmayr A, Aigner E, Huber-Schönauer U, et al. Relations of vitamin D status, gender and type 2 diabetes in middle-aged Caucasians. Acta Diabetol, 2015, 52(1):39-46.
40. Parik SJ, Edelman M, Uwaifo GI, et al. The relationship between obesity and serum 1, 25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab, 2004, 89(3): 1196-1199.
41. Wortsman J, Matsucka LY, Chen TC, et al. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr, 2000, 72(3): 690-693.
42. 王芳田, 冬梅, 童平, 等.老年2型糖尿病患者血清25羟维生素D与能量代谢关系的研究.中国糖尿病杂志, 2013, 21(8): 709-712.
43. Liu S, Song Y, Ford ES, et al. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. Women. Diabetes Care, 2005, 28(12): 2926-2932.
44. Reinbothe TM, Alkayyali S, Ahlqvist E, et al. The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes. Diabetologia, 2013, 56(2): 340-349.

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Effects of Vitamin D Supplementation on Glycaemic Control, Insulin Resistance and β Cell Function in Type 2 Diabetes Mellitus: A Meta-analysis

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