THE IMPACT OF DIFFERENT REGIMENS OF VITAMIN D3 ON GLUCOSE HOMEOSTASIS IN TYPE 2 DIABETIC PATIENTS
Objective: Vitamin D has a role in the regulation of pancreatic β-cell function and insulin sensitivity. Accordingly, Vitamin D deficiency is considered to be a risk factor for the development of type 2 diabetes mellitus (T2DM) and its complications. Therefore, the aim of the study was to assess and compare the effect of different regimens of Vitamin D3 on glucose homeostasis in patients with T2DM.
Methods: The study included 80 patients with T2DM taking oral antidiabetic drugs. The patients were randomized to receive antidiabetic drugs alone or with different regimens of Vitamin D3 for 3 months. Vitamin D3-treated patients were supplemented by either daily oral 4000 IU Vitamin D3, weekly oral 50,000 IU Vitamin D3, or a single parenteral dose of 300,000 IU Vitamin D3. In addition to the assessment of patient characteristics, laboratory measurements of serum creatinine, blood urea, total and ionized calcium, serum phosphorus, fasting blood glucose, fasting serum insulin, homeostasis model assessment of insulin resistance, hemoglobin A1c, and 25(OH) Vitamin D levels were measured at the beginning and after 3 months.
Results: After 3 months, the increased Vitamin D levels resulting from the daily and weekly oral doses of Vitamin D3 caused a significant decrease in metabolic parameters, whereas the parenteral dose demonstrated a non-significant decrease.
Conclusion: Oral daily and weekly doses of Vitamin D3 could improve glucose homeostasis equally in patients with T2DM and better than a single parenteral dose of Vitamin D3.
2. Kalsi A, Singh S, Taneja N, Kukal S, Mani S. Current treatment for Type2 diabetes, their side effects and possible complementary treatments. Int J Pharm Pharm Sci 2015;3:13-8.
3. Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008;88:1322-35.
4. Santos RKF, Brandão-Lima PN, Tete RMDD, Freire ARS, Pires LV. Vitamin D ratio and glycaemic control in individuals with Type 2 diabetes mellitus: A systematic review. Diabetes Metab Res Rev 2018;34: 1-11.
5. Kostoglou-Athanassiou I, Athanassiou P, Gkountouvas A, Kaldrymides P. Vitamin D and glycemic control in diabetes mellitus Type 2. Ther Adv Endocrinol Metab 2013;4:122-8.
6. Yu JR, Lee SA, Lee JG, Seong GM, Ko SJ, Koh G, et al. Serum Vitamin D status and its relationship to metabolic parameters in patients with Type 2 diabetes mellitus. Chonnam Med J 2012;48:108-15.
7. Saif-Elnasr M, Ibrahim IM, Alkady MM. Role of Vitamin D on glycemic control and oxidative stress in Type 2 diabetes mellitus. J Res Med Sci 2017;22:22.
8. Alam U, Arul-Devah V, Javed S, Malik RA. Vitamin D and diabetic complications: True or false prophet? Diabetes Ther 2016;7:11-26.
9. Abbas RS, Abdulridha MK, Shafek MA. Clinical evaluation of potential anti-inflammatory effect of Vitamin D3 adjuvant therapy for chronic asthma in iraqi patients. Int J Pharm Pharm Sci 2017;9:139-44.
10. Sung CC, Liao MT, Lu KC, Wu CC. Role of Vitamin D in insulin resistance. J Biomed Biotechnol 2012;2012:634195.
11. Johnson JA, Grande JP, Roche PC, Kumar R. Immunohistochemical localization of the 1,25(OH)2D3 receptor and calbindin D28k in human and rat pancreas. Am J Physiol 1994;267:E356-60.
12. Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE, et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol 2004;89-90:121-5.
13. Maestro B, Molero S, Bajo S, Dávila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxy Vitamin D(3). Cell Biochem Funct 2002;20:227-32.
14. Chagas CE, Borges MC, Martini LA, Rogero MM. Focus on Vitamin D, inflammation and Type 2 diabetes. Nutrients 2012;4:52-67.
15. Li X, Liu Y, Zheng Y, Wang P, Zhang Y. The effect of Vitamin D supplementation on glycemic control in Type 2 diabetes patients: A systematic review and meta-analysis. Nutrients 2018;10:E375.
16. Dwivedi A, Gupta B, Tiwari S, Pratyush DD, Singh S, Singh SK, et al. Parenteral Vitamin D supplementation is superior to oral in Vitamin D insufficient patients with Type 2 diabetes mellitus. Diabetes Metab Syndr 2017;11 Suppl 1:S373-S375.
17. Shaseb E, Tohidi M, Abbasinazari M, Khalili D, Talasaz AH, Omrani H, et al. The effect of a single dose of Vitamin D on glycemic status and C-reactive protein levels in Type 2 diabetic patients with ischemic heart disease: A randomized clinical trial. Acta Diabetol 2016;53:575-82.
18. Foroughi M, Maghsoudi Z, Askari G. The effect of vitamin D supplementation on blood sugar and different indices of insulin resistance in patients with non-alcoholic fatty liver disease (NAFLD). Iran J Nurs Midwifery Res 2016;21:100-4.
19. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, et al. Blood 25-hydroxy Vitamin D levels and incident Type 2 diabetes: A meta-analysis of prospective studies. Diabetes Care 2013;36:1422-8.
20. Parker J, Hashmi O, Dutton D, Mavrodaris A, Stranges S, Kandala NB, et al. Levels of Vitamin D and cardiometabolic disorders: Systematic review and meta-analysis. Maturitas 2010;65:225-36.
21. Heaney RP, Armas LA, Shary JR, Bell NH, Binkley N, Hollis BW, et al 25-hydroxylation of Vitamin D3: Relation to circulating Vitamin D3 under various input conditions. Am J Clin Nutr 2008;87:1738-42.
22. Bhagatwala J, Zhu H, Parikh SJ, Guo DH, Kotak I, Huang Y, et al. Dose and time responses of Vitamin D biomarkers to monthly Vitamin D3 supplementation in overweight/obese African Americans with suboptimal Vitamin D status: A placebo controlled randomized clinical trial. BMC Obes 2015;2:27.
23. Whyte MP, Haddad JG Jr. Walters DD, Stamp TC. Vitamin D bioavailability: Serum 25-hydroxy Vitamin D levels in man after oral, subcutaneous, intramuscular, and intravenous Vitamin D administration. J Clin Endocrinol Metab 1979;48:906-11.
24. Hashemipour S, Ghazi AA, Mehrtash B, Yazdi MA. Effect of different doses of parenteral Vitamin D3 on serum 25(OH)D concentrations. DARU 2015;17:26-9.
25. Diamond TH, Ho KW, Rohl PG, Meerkin M. Annual intramuscular injection of a megadose of cholecalciferol for treatment of Vitamin D deficiency: Efficacy and safety data. Med J Aust 2005;183:10-2.
26. Din I, Majid S, Rashid F, Hussain I, Koul RK, Qadir J, et al. Combinatorial effect of leptin, tumor necrosis factor-?lpha, and Vitamin D in progression of Type 2 diabetes in kashmiri population. Asian J Pharm Clin Res 2018;11:477-81.
27. Tabesh M, Azadbakht L, Faghihimani E, Tabesh M, Esmaillzadeh A. Effects of calcium-Vitamin D co-supplementation on metabolic profiles in Vitamin D insufficient people with Type 2 diabetes: A randomised controlled clinical trial. Diabetologia 2014;57:2038-47.
28. Krul-Poel YH, Westra S, ten Boekel E, ter Wee MM, van Schoor NM, van Wijland H, 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;38:1420-6.
29. Witham MD, Dove FJ, Dryburgh M, Sugden JA, Morris AD, Struthers AD, et al. The effect of different doses of Vitamin D(3) on markers of vascular health in patients with Type 2 diabetes: A randomised controlled trial. Diabetologia 2010;53:2112-9.
30. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low Vitamin D levels. Diabet Med 2008;25:320-5.
31. George PS, Pearson ER, Witham MD. Effect of Vitamin D supplementation on glycaemic control and insulin resistance: A systematic review and meta-analysis. Diabet Med 2012;29:e142-50.
32. Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM. The effect of improved serum 25-hydroxyvitamin D status on glycemic control in diabetic patients: A meta-analysis. J Clin Endocrinol Metab 2017;102:3097-110.
33. Talaei A, Mohamadi M, Adgi Z. The effect of Vitamin D on insulin resistance in patients with Type 2 diabetes. Diabetol Metab Syndr 2013;5:8.
34. Upreti V, Maitri V, Dhull P, Handa A, Prakash MS, Behl A, et al. Effect of oral Vitamin D supplementation on glycemic control in patients with Type 2 diabetes mellitus with coexisting hypovitaminosis D: A parellel group placebo controlled randomized controlled pilot study. Diabetes Metab Syndr 2018;12:509-12.
35. Jehle S, Lardi A, Felix B, Hulter HN, Stettler C, Krapf R, 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. Swiss Med Wkly 2014;144:w13942.
36. Norman AW. Minireview: Vitamin D receptor: New assignments for an already busy receptor. Endocrinology 2006;147:5542-8.
37. Harinarayan CV. Vitamin D and diabetes mellitus. Hormones (Athens) 2014;13:163-81.
38. Fujita T, Palmieri GM. Calcium paradox disease: Calcium deficiency prompting secondary hyperparathyroidism and cellular calcium overload. J Bone Miner Metab 2000;18:109-25.
39. Dunlop TW, Väisänen S, Frank C, Molnár F, Sinkkonen L, Carlberg C, et al. The human peroxisome proliferator-activated receptor delta gene is a primary target of 1alpha,25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol 2005;349:248-60.
40. Wei Y, Sowers JR, Clark SE, Li W, Ferrario CM, Stump CS, et al. Angiotensin II-induced skeletal muscle insulin resistance mediated by NF-kappaB activation via NADPH oxidase. Am J Physiol Endocrinol Metab 2008;294:E345-51.
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