Vitamin D and Type 2 Diabetes Mellitus: Role in Insulin Resistance, Glycemic Control and Long Term Complications

  • Indah Sapta Wardani Universitas Mataram
  • Aliza Raudatin Sahly
  • Indana Eva Ajmala
  • Dewi Suryani


Vitamin D has a number of roles in various body systems with receptors scattered in many organs,1,2 showing a link between vitamin D and several chronic diseases such as cancer, diabetes and autoimmune disease.3,4 Several studies have shown the role of vitamin D in type 2 diabetes in controlling blood sugar levels and HbA1c levels. Vitamin D plays a role in increasing insulin sensitivity and secretion and suppressing inflammation in type 2 diabetes. Vitamin D has a protective role in various complications of type 2 diabetes, including diabetic nephropathy, diabetic neuropathy and diabetic retinopathy.5 Monitoring of vitamin D levels and vitamin D supplementation have a therapeutic role to controlling glycemic blood glucose and prevent complications in type 2.6


1. Holick MF. The D-Lightful Vitamin D for Health. J Med Biochem (2013) 32:1–58 doi: 10.2478/v10011-012-0025-y
2. Holick MF. Vitamin D deficiency. The New England journal of medicine. 2007; 357(3):266–281. https:// PMID: 17634462
3. Martin T, Campbell RK. Vitamin D and Diabetes. Diabetes Spectr (2011) 24 (2):113–8. doi: 10.2337/diaspect.24.2.113
4. Holick MF, Chen TC. Vitamin D Deficiency: A Worldwide Problem With Health Consequences. Am J Clin Nutr (2008) 87(4):1080S–6S. doi: 10.1093/ ajcn/87.4.1080S
5. Zakhary CM, Rushdi H, Hamdan JA, Youssef KN, Khan A, Abdalla MA, Khan S. Protective Role of Vitamin D Therapy in Diabetes Mellitus Type II. Cureus. 2021 Aug 20;13(8):e17317. doi: 10.7759/cureus.17317. PMID: 34567869; PMCID: PMC8451532.
6. 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. doi: 10.1210/ jc.2017-01024
7. Pittas AG, Harris SS, Stark PC, Dawson-Hughes B. The effects of calcium and vitamin D supplementation on blood glucose and markers of inflammation in nondiabetic adults. Diabetes care. 2007; 30 (4):980–986. PMID: 17277040
8. Talaei A, Mohamadi M, Adgi Z. The effect of vitamin D on insulin resistance in patients with type 2 diabetes. Diabetology & metabolic syndrome. 2013; 5(1):8.
9. Cojic? MM. The Role of Vitamin D in Treating Patients With Type 2 Diabetes Mellitus. Acta Med Median (2019) 58:116–24. doi: 10.5633/amm.2019.0116
10. 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. doi: 10.4103/1735-1995.200278
11. Ahmed LH, Butler AE, Dargham SR, et al.: Association of vitamin D2 and D3 with type 2 diabetes complications. BMC Endocr Disord. 2020, 20:65. 10.1186/s12902-020-00549-w
12. Handono, Kusworini., Dkk. 2018. Vitamin D dan Autoimunitas. [Books Google]. Malang: UB Press
13. Bikle, D. Vitamin D Metabolism, Mechanism of Action, and Clinical Application. Chemical and Biology Journal. 2014.
14. Bickle, D. Vitamin D : Production, Metabolism, and Mechanism of Action. Journal of Univesity of California. 2017.
15. Pusparini. 2018. Defisiensi Vitamin D Terhadap Penyakit. Indonesian Journal of Clinical Pathology and Medical Laboratory. Volume21. Nomor 1. Available at: 5
16. Daniel, B. Vitamin D : Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level. Journal of Endocrine Society. 2020;Vol. 4.
17. Christakos, S dkk. Vitamin D : METABOLISM, Molecular Mechanism of Action, and Pleiotropic Effects. American Physiological Journal. 2015.
18. Dankers, Wendy. et al. 2017. Vitamin D in Autoimmunity: Molecular Mechanism and Therapeutic Potential. Frontiers in Immunology. 7:697. Available at :
19. Bellan, M. et al. Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Disease. MDPI. Available at :
20. Prietl, Babara. et al. 2013. Vitamin D and Immune Function. MDPI. Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, A 8036 Graz, Austria. Available at :
21. Christakos, Sylvia, et al. "Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects." Physiological reviews 96.1 (2016): 365-408.
22. Daniel, B. Vitamin D : Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level. Journal of Endocrine Society. 2020;Vol. 4.
23. Pajor, I dkk. Analysii of Association Between Vitamin D Deficiency and Insulin Resistance. Journal of Nucleic Acid Biochemistry Departement of Medical Unieversity of Lods. 2019
24. PERKENI. Pedoman pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 Dewasa di Indonesia. 2021.
25. Wild S, Roglic G, Green A, Sicree R, King H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004, 27:1047-53. 10.2337/diacare.27.5.1047
26. Kementrian Kesehatan Republik Indonesia. Tetap Produktif, Cegah Dan Atasi Diabetes Mellitus. pusat data dan informasi kementrian kesehatan RI. 2020.
27. Leahy JL: Pathogenesis of type 2 diabetes mellitus . Arch Med Res. 2005, 36:197-209. 10.1016/j.arcmed.2005.01.003
28. Seshandri, K dkk. Role of Vitamin D in Diabetes. Journal of Endrocrinology and Metabolism. 2011.
29. Sanda, A dkk. Analysis of Vitamin D in Patients With Type 2 Diabetes Mellitus. Indonesian Journal of Clinical Pathology. 2019; Vol 25 No.2.
30. Shaheen, S dkk. Association Between Type 2 Diebetes Mellitus and Hypovitaminosis D. International Journal of Clinical Biochemistry and Research. 2017.
31. Kolb H, Mandrup-Poulsen T: An immune origin of type 2 diabetes? . Diabetologia. 2005, 48:1038-50. 10.1007/s00125-005-1764-9
32. Pittas AG, Joseph NA, Greenberg AS: Adipocytokines and insulin resistance. J Clin Endocrinol Metab. 2004, 89:447-52. 10.1210/jc.2003-031005
33. Sung CC, Liao MT, Lu KC, Wu CC: Role of vitamin D in insulin resistance . J Biomed Biotechnol. 2012, 2012:634195. 10.1155/2012/634195
34. Christakos S, Liu Y: Biological actions and mechanism of action of calbindin in the process of apoptosis . J Steroid Biochem Mol Biol. 2004, 89-90:401-4. 10.1016/j.jsbmb.2004.03.007
35. Maestro B, Campión J, Dávila N, Calle C: Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J. 2000, 47:383-91. 10.1507/endocrj.47.383
36. Dunlop TW, Väisänen S, Frank C, Molnár F, Sinkkonen L, Carlberg C: The human peroxisome proliferatoractivated receptor delta gene is a primary target of 1-alpha, 25-dihydroxyvitamin D3 and its nuclear receptor. J Mol Biol. 2005, 349:248-60. 10.1016/j.jmb.2005.03.060
37. 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. 10.1152/ajpendo.1994.267.3.E356
38. Hu Z, Chen J, Sun X, Wang L, Wang A: Efficacy of vitamin D supplementation on glycemic control in type 2 diabetes patients: a meta-analysis of interventional studies. Medicine (Baltimore). 2019, 98:e14970. 10.1097/MD.0000000000014970
39. Angellotti, E dkk. Vitamin D Supplementation in Patients With Type 2 Diabetes : The Vitamin D for Established Type 2 Diebetes (DDM2) Study. Journal of the Endocrine Society. 2018.
40. 9. Papaioannou I, Pantazidou G, Kokkalis Z, Georgopoulos N, Jelastopulu E. Vitamin D Deficiency in Elderly With Diabetes Mellitus Type 2: A Review. Cureus [Internet]. 2021 Jan 5 [cited 2022 Jan 15];13(1). Available from: vitamin-d-deficiency-in-elderly-with-diabetes-mellitus-type-2-a- review
41. Shillo P, Selvarajah D, Greig M, et al.: Reduced vitamin D levels in painful diabetic peripheral neuropathy . Diabet Med. 2019, 36:44-51. 10.1111/dme.13798
42. Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D: New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002, 13:100-5. 10.1016/s1043-2760(01)00547-1
43. Basit A, Basit KA, Fawwad A, et al.: Vitamin D for the treatment of painful diabetic neuropathy . BMJ Open Diabetes Res Care. 2016, 4:e000148. 10.1136/bmjdrc-2015-000148
44. Shehab D, Al-Jarallah K, Abdella N, Mojiminiyi OA, Al Mohamedy H: Prospective evaluation of the effect of short-term oral vitamin d supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract. 2015, 24:250-6. 10.1159/000375304
45. Zelnick LR, Weiss NS, Kestenbaum BR, et al.: Diabetes and CKD in the United States Population, 2009-2014 . Clin J Am Soc Nephrol. 2017, 12:1984-90. 10.2215/CJN.03700417
46. Afkarian M, Zelnick LR, Hall YN, Heagerty PJ, Tuttle K, Weiss NS, de Boer IH: Clinical manifestations of 2021 Zakhary et al. Cureus 13(8): e17317. DOI 10.7759/cureus.17317 7 of 8 kidney disease among US adults with diabetes, 1988-2014. JAMA. 2016, 316:602-10. 10.1001/jama.2016.10924
47. de Borst MH, Hajhosseiny R, Tamez H, Wenger J, Thadhani R, Goldsmith DJ: Active vitamin D treatment for reduction of residual proteinuria: a systematic review. J Am Soc Nephrol. 2013, 24:1863-71. 10.1681/ASN.2013030203
48. Agarwal R, Acharya M, Tian J, et al.: Antiproteinuric effect of oral paricalcitol in chronic kidney disease . Kidney Int. 2005, 68:2823-8. 10.1111/j.1523-1755.2005.00755.
49. Anderson RE, Rapp LM, Wiegand RD: Lipid peroxidation and retinal degeneration . Curr Eye Res. 1984, 3:223-7. 10.3109/02713688408997203
50. Zhang J, Upala S, Sanguankeo A: Relationship between vitamin D deficiency and diabetic retinopathy: a meta-analysis. Can J Ophthalmol. 2017, 52:219-24. 10.1016/j.jcjo.2016.10.004
51. Portero McLellan KC, Wyne K, Villagomez ET, Hsueh WA. Therapeutic interventions to reduce the risk of progression from prediabetes to type 2 diabetes mellitus. Therapeutics and clinical risk management. 2014; 10:173–188. PMID: 2467224
52. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient—a randomised, placebo-controlled trial. The British journal of nutrition. 2010; 103(4):549–555. S0007114509992017 PMID: 19781131
53. Sheth JJ, Shah A, Sheth FJ, Trivedi S, Lele M, Shah N, et al. Does vitamin D play a significant role in type 2 diabetes? BMC endocrine disorders. 2015; 15:5. PMID: 25887335
54. 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, 10:375. 10.3390/nu10030375
55. 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. The American journal of physiology. 1994; 267 (3 Pt 1):E356–360. PMID: 7943215
56. Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE, et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. The Journal of steroid biochemistry and molecular biology. 2004; 89-90(1–5):121–125. PMID: 15225758
57. Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clinical chemistry. 2013; 59(2):381–391. 1373/clinchem.2012.193003 PMID: 23232064
58. Kayaniyil S, Retnakaran R, Harris SB, Vieth R, Knight JA, Gerstein HC, et al. Prospective associations of vitamin D with beta-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study. Diabetes. 2011; 60(11):2947–2953. PMID: 21911752
59. Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic beta 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. The American journal of clinical nutrition. 2011; 94(2):486–494. PMID: 21715514
60. Zeitz U, Weber K, Soegiarto DW, Wolf E, Balling R, Erben RG. Impaired insulin secretory capacity in mice lacking a functional vitamin D receptor. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2003; 17(3):509–511.
61. Lemieux P, John Weisnagel S, Caron AZ, Julien AS, Morisset AS, Carreau AM, Poirier J, Tchernof A, Robitaille J, Bergeron J, Marette A, Vohl MC, Gagnon C. Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomised, placebo-controlled trial. Eur J Endocrinol [Internet]. 2019 Sep 1 [cited 2022 Jan16];181(3):287–99. Available from: 0156.xml
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