The role of metformin on serum vitamin B12 levels in patients with type 2 diabetes mellitus

Year 2015, Volume: 1 Issue: 1, 1 - 7, 04.03.2015

Mitra Niafar Behrad Jamali Nasrin Lotfibakhshaiesh Naser Aghamohammadzadeh Nader Nader

https://doi.org/10.18621/eurj.2015.1.1.1

Cited By: 3

Abstract

Objective. To evaluate the vitamin B12 (VB12) deficiency in patients with type-2 diabetes mellitus (DM-2) using metformin or other hypoglycemic agents. Methods. 400 patients with DM-2 were divided into two arms (N=200/group); 1) those receiving metformin (MET) for at least six months and 2) those receiving  hypoglycemic agents other than metformin (OHA). Serum VB12 concentrations were measured. Data were analyzed by using two-sample t-test for numerical data and chi-square with logistic regression analysis for categorical data. Numerical values were expressed as means ± standard deviations. Null hypotheses were rejected at P-values <0.05. Results. Definite biochemical VB12 deficiency (<148 pmol/L) was found in 29/200 (14.5%) of the MET group while it was observed in 4/200 (2%) in the OHA group (P<0.001). Similarly, possible VB12 deficiency (serum concentrations <185 pmol/L) was found in 39 (19.2%) of the MET group and 12 (6%) in the OHA group (p<0.001). There was positive correlation between low VB12 level and metformin administration (R²=0.26, p<0.001). Conclusion. Patients with DM-2 on metformin had lower VB12 levels than those on other hypoglycemic drugs. The relation between VB12 deficiency and metformin therapy indicates the need for periodic measurement of serum VB12 levels in patients treated with metformin.

Keywords

Oral medications, type-2 diabetes, metabolic syndrome, HbA1C, diabetic neuropathy

References

• American Diabetes A. Standards of medical care in diabetes-- 2014. Diabetes Care. 2014;37 Suppl 1:S14-80.
• Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574-9.
• Nobes JP, Langley SE, Klopper T, Russell-Jones D, Laing RW. A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy. BJU Int. 2012;109(10):1495-502.
• Pantalone KM, Kattan MW, Yu C, Wells BJ, Arrigain S, Nutter B, et al. The risk of overall mortality in patients with Type 2 diabetes receiving different combinations of sulfonylureas and metformin: a retrospective analysis. Diabet Med. 2012;29(8):1029-35.
• Bailey CJ. Diabetes: insulin plus metformin for T2DM--are there benefits? Nat Rev Endocrinol. 2012;8(8):449-50.
• de Jager J, Kooy A, Lehert P, Wulffele MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181.
• Kumthekar AA, Gidwani HV, Kumthekar AB. Metformin associated B12 deficiency. J Assoc Physicians India. 2012;60:58- 60.
• Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-23.
• Evatt ML, Terry PD, Ziegler TR, Oakley GP. Association between vitamin B12-containing supplement consumption and prevalence of biochemically defined B12 deficiency in adults in NHANES III (third national health and nutrition examination survey). Public Health Nutr. 2010;13(1):25-31.
• Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2011;83(12):1425-30.
• Andres E, Affenberger S, Zimmer J, Vinzio S, Grosu D, Pistol G, et al. Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Clin Lab Haematol. 2006;28(1):50-6.
• Andres E, Federici L, Sibilia J. Myelopathy in Sjogren's syndrome: a causative role for cobalamin (vitamin B12) deficiency. Drugs. 2006;66(5):729.
• Federici L, Henoun Loukili N, Zimmer J, Affenberger S, Maloisel F, Andres E. [Update of clinical findings in cobalamin deficiency: personal data and review of the literature]. Rev Med Interne. 2007;28(4):225-31.
• Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006;166(18):1975-9.
• van Rossum AP, Gunnewiek JK, Verheijen FM, Vlasveld LT, Castel A, Fouraux MA. Introduction of a new cobalamin (vitamin B12) assay: lessons from a flawed validation study. Clin Chem Lab Med. 2011;49(1):105-9.
• Salwen mJ. Vitamins and trace elements. In: McPherson RA PM, ed. Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadephia, PA: Elsevier Saunders; 2011.
• Nervo M, Lubini A, Raimundo FV, Faulhaber GA, Leite C, Fischer LM, et al. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil. Rev Assoc Med Bras. 2011;57(1):46-9.
• Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP, Jr. Association of biochemical B(1)(2) deficiency with metformin therapy and vitamin B(1)(2) supplements: the National Health and Nutrition Examination Survey, 1999-2006. Diabetes Care. 2012;35(2):327-33.
• Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2003;254(5):455-63.
• Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R. 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.
• 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.
• Scarpello JH, Hodgson E, Howlett HC. Effect of metformin on bile salt circulation and intestinal motility in type 2 diabetes mellitus. Diabet Med. 1998;15(8):651-6.
• Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):25-33.
• Johnson MA, Hawthorne NA, Brackett WR, Fischer JG, Gunter EW, Allen RH, et al. Hyperhomocysteinemia and vitamin B- 12 deficiency in elderly using Title IIIc nutrition services. Am J Clin Nutr. 2003;77(1):211-20.
• Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60(1):2-11.
• Pennypacker LC, Allen RH, Kelly JP, Matthews LM, Grigsby J, Kaye K, et al. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc. 1992;40(12):1197-204.
• Jabbar A, Yawar A, Waseem S, Islam N, Ul Haque N, Zuberi L, et al. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008;58(5):258-61.
• Calvo Romero JM, Ramiro Lozano JM. Vitamin B(12) in type 2 diabetic patients treated with metformin. Endocrinol Nutr. 2012;59(8):487-90.
• Liu KW, Dai LK, Ho W, Lau E, Woo J. Metformin-associated vitamin B12 deficiency in the elderly. Asian J Gerontol Geriatry. 2011;6:82-7.
• American Diabetes A. Standards of medical care in diabetes-- 2010. Diabetes Care. 2010;33 Suppl 1:S11-61.
• Andres E, Vidal-Alaball J, Federici L, Loukili NH, Zimmer J, Kaltenbach G. Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy. Eur J Intern Med. 2007;18(6):456-62.