Prevalence of Vitamin B12 Deficiency and its Associated Factors among Patients with Type 2 Diabetes Mellitus on Metformin from a District in Malaysia
DOI:
https://doi.org/10.15605/jafes.035.02.03Keywords:
Vitamin B12, metformin, deficiency, type 2 diabetes mellitus, type 2 DMAbstract
*Visual Abstracts prepared by Dr. Jerico GutierrezIntroduction. Vitamin B12 deficiency is more common among metformin-treated subjects although the prevalence is variable. Many factors have been associated with this. The aim of this study is to determine the prevalence of vitamin B12 deficiency and its associated factors among patients with type 2 diabetes mellitus (DM) who are on metformin.
Methodology. A total of 205 patients who fit eligibility criteria were included in the study. A questionnaire was completed, and blood was drawn to study vitamin B12 levels. Vitamin B12 deficiency was defined as serum B12 level of ≤300 pg/mL (221 pmol/L).
Results. The prevalence of vitamin B12 deficiency among metformin-treated patients with type 2 DM patients was 28.3% (n=58). The median vitamin B12 level was 419 (±257 ) pg/mL. The non-Malay population was at a higher risk for metformin-associated vitamin B12 deficiency [adjusted odds ratio (OR) 3.86, 95% CI: 1.836 to 8.104, p<0.001]. Duration of metformin use of more than five years showed increased risk for metformin-associated vitamin B12 deficiency (adjusted OR 2.06, 95% CI: 1.003 to 4.227, p=0.049).
Conclusion. Our study suggests that the prevalence of vitamin B12 deficiency among patients with type 2 diabetes mellitus on metformin in our population is substantial. This is more frequent among the non-Malay population and those who have been on metformin for more than five years.
Downloads
References
Nervo M, Lubini A, Raimundo FV, et al. Vitamin B12 in metformin-treated diabetic patients: A cross-sectional study in Brazil. Rev Assoc Med Bras (1992). 2011;57(1):46-9. https://www.ncbi.nlm.nih.gov/pubmed/21390459.
Tomkin GH, Hadden DR, Weaver JA, Montgomery DAD. Vitamin B12 status of patients on long-term metformin therapy. Br Med J. 1971;2(5763):685-7. https://www.ncbi.nlm.nih.gov/pubmed/5556053. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1796258. https://doi.org/10.1136/bmj.2.5763.685.
Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GPJ. Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: The National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35(2):327-33. https://www.ncbi.nlm.nih.gov/pubmed/22179958. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263877. https://doi.org/10.2337/dc11-1582.
Romero JMC, Lozano JMR. Vitamin B(12) in type 2 diabetic patients treated with metformin. Endocrinol Nutr. 2012;59(8):487-90. https://www.ncbi.nlm.nih.gov/pubmed/22981397. https://doi.org/10.1016/j.endonu.2012.06.005.
Pongchaidecha M, Srikusalanukul V, Chattananon A, Tanjariyaporn S. Effect of metformin on plasma homocysteine, vitamin B12 and folic acid: A cross-sectional study in patients with type 2 diabetes mellitus. J Med Assoc Thai. 2004;87(7):780-7. https://www.ncbi.nlm.nih.gov/pubmed/15521233.
Berchtold P, Bolli P, Arbenz U, Keiser G. Disturbance of intestinal absorption following metformin therapy (observations on the mode of action of biguanides). Diabetologia. 1969;5(6):405-12. https://www.ncbi.nlm.nih.gov/pubmed/5372893. https://doi.org/10.1007/BF00427979.
Caspary WF, Zavada I, Reimold W, Deuticke U, Emrich D, Willms B. Alteration of bile acid metabolism and vitamin-B12-absorption in diabetics on biguanides. Diabetologia. 1977;13(3):187-93. https://www.ncbi.nlm.nih.gov/pubmed/873086. https://doi.org/10.1007/BF01219698.
Bell DSH. Metformin-induced vitamin B12 deficiency presenting as a pe¬ripheral neuropathy. South Med J. 2010;103(3):265-7. https://www.ncbi.nlm.nih.gov/pubmed/20134380. https://doi.org/10.1097/SMJ.0b013e3181ce0e4d.
Ko SH, Ko SH, Ahn YB, et al. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci. 2014;29(7):965-72. https://www.ncbi.nlm.nih.gov/pubmed/25045229. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101785. https://doi.org/10.3346/jkms.2014.29.7.965.
Shaw LM, Strømme JH, London JL, Theodorsen L. International Federation of Clinical Chemistry (IFCC), Scientific Committee, Analytical Section. IFCC methods for the measurement of catalytic concentration of enzymes. Part 4. IFCC method for gamma-glutamyltransferase [(gamma-glutamyl)-peptide: amino acid gamma-glutamyltransferase, EC 2.3.2.2]. J Clin Chem Clin Biochem. 1983;21(10);633-46. https://www.ncbi.nlm.nih.gov/pubmed/6139407.
Liu Q, Li S, Quan H, Li J. Vitamin B12 status in metformin treated patients: Systematic review. PLoS One. 2014; 9(6):e100379. https://www.ncbi.nlm.nih.gov/pubmed/24959880. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069007. https://doi.org/10.1371/journal.pone.0100379.
Khan A, Shafiq I, Shah MH. Prevalence of vitamin B12 deficiency in patients with type 2 diabetes mellitus on metformin: A study from Khyber Pakhtunkhwa. Cureus. 2017;9(8):e1577. https://www.ncbi.nlm.nih.gov/pubmed/29057189. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647126. https://doi.org/10.7759/cureus.1577.
Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997;337(20):1441-8. https://www.ncbi.nlm.nih.gov/pubmed/9358143. https://doi.org/10.1056/NEJM199711133372007.
Lindenbaum J. Folate and vitamin B12 deficiencies in alcoholism. Semin. Hematol. 1980;17(2):119-29. https://www.ncbi.nlm.nih.gov/pubmed/6990497.
Long AN, Atwell CL, Yoo W, Solomon SS. Vitamin B(12) deficiency associated with concomitant metformin and proton pump inhibitor use. Diabetes Care. 2012;35(12):e84. https://www.ncbi.nlm.nih.gov/pubmed/23173145. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3507616. https://doi.org/10.2337/dc12-0980.
Daniel WW. Biostatistics: A foundation for analysis in the health sciences. 7th ed. New York: John Wiley & Sons, 1999.
Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term metformin use and vitamin B12 deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-61. https://www.ncbi.nlm.nih.gov/pubmed/26900641. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880159. https://doi.org/10.1210/jc.2015-3754.
Pflipsen MC, Oh RC, Saguil A, et al. The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: A cross-sectional study. J Am Board Fam Med. 2009;22(5):528-34. https://www.ncbi.nlm.nih.gov/pubmed/19734399. https://doi/org/10.3122/jabfm.2009.05.090044.
Berchtold P, Dahlqvist A, Gustafson A, Asp NG. Effects of a biguanide (metformin) on vitamin B12 and folic acid absorption and intestinal enzyme activities. Scand J Gastroenterol. 1971;6(8):751-4. https://www.ncbi.nlm.nih.gov/pubmed/5139118. https://doi.org/10.3109/00365527109179948.
Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23(9):1227-31. https://www.ncbi.nlm.nih.gov/pubmed/10977010. https://doi.org/10.2337/diacare.23.9.1227.
Fernandes-Costa F, Metz J. A comparison of serum transcobalamin levels in white and black subjects. Am J Clin Nutr. 1982;35(1):83-6. https://www.ncbi.nlm.nih.gov/pubmed/7064880. https://doi.org/10.1093/ajcn/35.1.83.
Ahmed MA, Muntingh G, Rheeder P. Vitamin B12 deficiency in metformin-treated type 2 diabetes patients, prevalence and association with peripheral neuropathy. BMC Pharmacol Toxicol. 2016;17:44. https://www.ncbi.nlm.nih.gov/pubmed/27716423. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054613. https://doi.org/10.1186/s40360-016-0088-3.
Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57(4):422-8. https://www.ncbi.nlm.nih.gov/pubmed/15135846. https://doi.org/10.1016/j.jclinepi.2003.08.015.
Ruscin JM, Page RL 2nd, Valuck RJ. Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 2002;36(5):812-6. https://www.ncbi.nlm.nih.gov/pubmed/11978157. https://doi.org/10.1345/aph.10325.
Hin H, Clarke R, Sherliker P, et al. Clinical relevance of low serum vitamin B12 concentrations in older people: The Banbury B12 study. Age Ageing 2006;35(4):416-22. https://www.ncbi.nlm.nih.gov/pubmed/16709605. https://doi.org/10.1093/ageing/afl033.
Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988; 318(26):1720-8. https://www.ncbi.nlm.nih.gov/pubmed/3374544. https://doi.org/10.1056/NEJM198806303182604.
Naha K, Dasari S, Vivek G, Prabhu M. Vitamin B12 deficiency: An unusu¬al cause for recurrent generalised seizures with pancytopaenia. BMJ Case Reports. 2012;10.1136/bcr-2012-006632. https://www.ncbi.nlm.nih.gov/pubmed/22948998. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543758. https://doi.org/10.1136/bcr-2012-006632.
Durand C, Mary S, Brazo P, Dollfus S. Psychiatric manifestations of vita¬min B12 deficiency: A case report. Encephale. 2003;29(6):560-5. https://www.ncbi.nlm.nih.gov/pubmed/15029091.
McKay DL, Perrone G, Rasmussen H, Dallal G, Blumberg JB. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. J Nutr. 2000;130(12):3090-6. https://www.ncbi.nlm.nih.gov/pubmed/11110875. https://doi.org/10.1093/jn/130.12.3090.
Wolters M, Hermann S, Hahn A. Effect of multivitamin supplementation on the homocysteine and methylmalonic acid blood concentrations in women over the age of 60 years. Eur J Nutr. 2005;44(3):183-92. https://www.ncbi.nlm.nih.gov/pubmed/15309436. https://doi.org/10.1007/s00394-004-0510-2.
Institute for Public Health 2020. National Health and Morbidity Survey (NHMS) 2019.: Non-communicable diseases, healthcare demand, and health literacy—Key Findings. http://iku.moh.gov.my/images/IKU/Document/REPORT/NHMS2019/Infographic_Booklet_NHMS_2019-English.pdf.
Published
How to Cite
Issue
Section
License
Journal of the ASEAN Federation of Endocrine Societies is licensed under a Creative Commons Attribution-NonCommercial 4.0 International. (full license at this link: http://creativecommons.org/licenses/by-nc/3.0/legalcode).
To obtain permission to translate/reproduce or download articles or use images FOR COMMERCIAL REUSE/BUSINESS PURPOSES from the Journal of the ASEAN Federation of Endocrine Societies, kindly fill in the Permission Request for Use of Copyrighted Material and return as PDF file to jafes@asia.com or jafes.editor@gmail.com.
A written agreement shall be emailed to the requester should permission be granted.