Serum Vitamin B12 Level in Type 2 Diabetes Patients on Metformin Therapy

Saman Ismail  Farajulla; Mohammed Qader  Meena

doi:10.56056/

Authors

Saman Ismail Farajulla MBChB, FIBMS (Int. Med.), KHCMS in Endocrinology & Diabetes; Hawler Teaching Hospital-Kurdistan region/Iraq
Mohammed Qader Meena MBChB, MIM, FRCP, MRCP, SCE (Endocrinology& Diabetes); Consultant internal medicine, Assistant professor at College of Medicine, HMU- Kurdistan region/Iraq

DOI:

https://doi.org/10.56056/

Keywords:

Glycemic control, Metformin, Type 2 diabetes mellitus, Vitamin B12

Abstract

Background and Objective: Type 2 diabetes mellitus is a common non-communicable disease all over the world. Metformin is an effective treatment option for diabetic patients. However, this option is frequently accompanied by vitamin B₁₂ deficiency. Therefore, we aimed to measure the prevalence of serum vitamin B12 deficiency in type 2 diabetic patients and recognize risk factors related to vitamin B₁₂ deficiency.

Methods: This study was a retrospective cross-sectional study implemented in Layla Qasim Diabetic Center in Erbil city-Kurdistan region/Iraq through six months from 1^st of October 2023 to 31^st of March 2024 on a sample of 100 type 2 diabetic patients. We investigated and analyzed patients' data. The vitamin B₁₂ deficiency was diagnosed regarding the center laboratory cutoff value of less than 191 pg/ml.

Results: The mean serum B₁₂ level of type 2 diabetic patients was (421.9 pg/ml); 21% had low serum B₁₂ levels. A significant association was observed between good glycemic control (i.e. HbA1c of less than 7.0%)¹ of type 2 diabetic patients and low serum B₁₂ level (p-value=0.04). No significant relationships existed between serum B₁₂ levels and other type 2 diabetic patients' characteristics (p>0.05).

Conclusions: The prevalence of serum vitamin B₁₂ deficiency among type 2 diabetic patients on metformin is within the acceptable range (i.e. serum vitamin B12 between 191-663 pg/ml). The strict glycemic control by high doses of metformin therapy for type 2 diabetic patients commonly leads to serum vitamin B₁₂ deficiency.

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References

1. American Diabetes Association Professional Practice Committee. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45(Suppl 1): S17-S38.

2. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: Global, regional, and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022; 183:109119.

3. Baena-Díez JM, Peñafiel J, Subirana I, Ramos R, Elosua R, Marín-Ibañez A, et al; FRESCO Investigators. Risk of Cause-Specific Death in Individuals with Diabetes: A Competing Risks Analysis. Diabetes Care 2016; 39(11):1987-1995.

4. Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjörnsdottir S, et al. Excess Mortality among Persons with Type 2 Diabetes. N Engl J Med 2015; 373(18):1720-1732.

5. World Health Organization. Diabetes. Geneva, Switzerland: World Health Organization; 2018. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes/

6. Ali NS, Allela OQ, Salih HM, Ahmed IH. Prevalence of Type 2 Diabetes Associated Complications in Kurdistan Region Iraq. J Basic Clin Pharma 2019; 10: 1-6.

7. Kim HJ, Noh JH, Moon MK, Choi SH, Ko SH, Rhee EJ, et al. A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors. J Diabetes Res 2024; 2024:8915591.

8. Blonde L, Dipp S, Cadena D. Combination glucose-lowering therapy plans in T2DM: case-based considerations. Adv Ther 2018; 35:939–965.

9. Lv Z and Guo Y. Metformin and Its Benefits for Various Diseases. Front Endocrinol 2020; 11:191.

10. Dutta S, Shah RB, Singhal S, Dutta SB, Bansal S, Sinha S, et al. Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes. Drug Des Devel Ther 2023; 17:1907-1932.

11. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci 2012; 122:253–270.

12. Lin Y, Wang K, Ma C, Wang X, Gong Z, Zhang R, et al. Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Front Aging Neurosci 2018; 10:227.

13. Cherney DZI, Lam TKT. A gut feeling for metformin. Cell Metab 2018; 28:808–810.

14. Bonnet F, Scheen A. Understanding and overcoming metformin gastrointestinal intolerance. Diabetes Obes Metab 2017; 19(4):473-481.

15. Ahmed MA. Metformin and Vitamin B12 Deficiency: Where Do We Stand? J Pharm Pharm Sci 2016; 19(3):382-398.

16. Stein J, Geisel J, Obeid R. Association between neuropathy and B-vitamins: A systematic review and meta-analysis. Eur J Neurol 2021; 28(6):2054-2064.

17. Elhadd T, Ponirakis G, Dabbous Z, Siddique M, Chinnaiyan S, Malik RA. Metformin Use Is Not Associated with B12 Deficiency or Neuropathy in Patients with Type 2 Diabetes Mellitus in Qatar. Front Endocrinol (Lausanne) 2018; 9:248.

18. Abu Jama’ah WJ, Alzu'bi MF, Alabbadi AR, Al Mrayat AM, Aldmour OA, Abu Abeeleh J, et al. Studying the association of metformin dose with peripheral neuropathy in diabetic patients at Jordanian Royal Medical Services. Eur Sci J 2016; 12(6):1-28.

19. Alvarez M, Sierra OR, Saavedra G, Moreno S. Vitamin B12 deficiency and diabetic neuropathy in patients taking metformin: a cross-sectional study. Endocr Connect 2019; 8(10):1324-1329.

20. Satyanarayana A, Balakrishna N, Pitla S, Reddy PY, Mudili S, Lopamudra P, Set al. Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia. PLoS One 2011; 6(11): e26747.

21. Ahmed SS, El-Hafez HAA, Mohsen M, El-Baiomy AA, Elkhamisy ET, El-Eshmawy MM. Is vitamin B12 deficiency a risk factor for gastroparesis in patients with type 2 diabetes Diabetol Metab Syndr 2023; 15(1):33.

22. Alshammari AN, Iqbal R, Baksh IP. Vitamin B12 deficiency and the knowledge and practice of physicians regarding screening for vitamin B12 deficiency among type 2 diabetic patients on metformin in selected hospitals in Riyadh, Saudi Arabia. J Family Med Prim Care 2019; 8(7):2306-2311.

23. Gao L, Ran X, Liu X, Shen X, Chen S, Liu F, et al. The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study. J Diabetes 2023; 15(9):765-776.

24. Alam MS, Kamrul-Hasan A, Kalam ST. Serum vitamin B12 status of patients with type 2 diabetes mellitus on metformin: A single-center cross-sectional study from Bangladesh. J Family Med Prim Care 2021; 10(6):2225-2229.

25. Abubakr GO, Hasan KM, Al-Rawy H, Hamid SF. Prevalence of B12 deficiency among patients with type 2 diabetes mellitus using Metformin in Sulaimani governorate /Kurdistan region of Iraq. AMJ 2020; 6 (1): 28-33.

26. Raqib TM, Mohammad NS. Prevalence of Vitamin B12 Deficiency in Patients with Type 2 Diabetes Mellitus on Metformin. DJM 2022; 23 (1): 22-32.

27. Mohammed AF, Al-Omer DK. Prevalence of Vitamin B12 Deficiency in Type 2 Diabetes Mellitus Patients on Metformin. TQMJ 2023; 26 (2): 32-41.

28. Damião CP, Rodrigues AO, Pinheiro MF, Cruz RA Filho, Cardoso GP, Taboada GF, et al. Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study. Sao Paulo Med J 2016; 134(6):473-479.

29. Almatrafi SB, Bakr EH, Almatrafi AA, Altayeb MM. Prevalence of vitamin B12 deficiency and its association with metformin-treated type 2 diabetic patients: A cross-sectional study. Human Nutrition & Metabolism 2022; 27: 200138.

30. Artasensi A, Pedretti A, Vistoli G, Fumagalli L. Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs. Molecules 2020; 25(8):1987.

31. Alhaji JH. Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries. Nutrients 2022; 14(10):2046.

32. Li W, Zhao J, Zhu LL, Peng YF. Serum vitamin B12 levels and glycemic fluctuation in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab 2022; 13:20420188221102800.