Serum Vitamin B12 Levels among Type 2 Diabetic Patients Maintained on Metformin Based Oral Anti-Diabetic Drugs - An Observational Study


Affiliations

  • Menzies School of Health Research, Translational Senior Research Officer, Darwin, 0810, Australia
  • St. John’s National Academy of Health Sciences, Internal Medicine, Bangalore, Karnataka, 560 034, India
  • University of Mysore, Department of Studies in Food Science and Nutrition, Mysore, Karnataka, 570 006, India

Abstract

The study was aimed to assess the serum vitamin B12 status of diabetic patients managed on metformin mono or combination therapy. A total of 45 patients (25 males; 20 females) diagnosed with type 2 diabetes for less than 3 years were enrolled into the study. Two groups were formed - metformin monotherapy or Gp1 (21 patients, mean age = 42.8 ± 6.82 years) and combination therapy group or Gp2 (24 patients, mean age = 42.6 ± 7.05 years). It was a self-control study wherein their serum vitamin B12 was measured at baseline (initial) and after 6 months (final). Demographic profile was obtained at baseline. Dietary intake of vitamin B12 was assessed by 3 days recall, while clinical manifestations of B12 deficiency and metformin dosages were obtained at initial and final period. Mean dietary intake of vitamin B12 was 1.16 ± 1.01 μg/day at baseline and 1.25 ± 1.15 μg/day at the sixth month, in the two groups. The mean serum B12 levels of group 1 and 2 at baseline were 347.54 ± 146.10, 293.47 ± 90.90 pg/ml, respectively and those at sixth month were 296.24 ± 144.45 and 239.32 ± 89.90 pg/ml respectively. The mean reduction in serum B12 was 51 and 54 pg/ml in Gp1 and Gp2 respectively, during the six-month observation period and the difference was statistically significant (P = Gp-1; 0.001, Gp-2; 0.002). An inverse relation was found between serum B12 and dosage of metformin. The proportion of patients with weakness, tingling/numbness in hands/feet increased markedly in the sixth month in both the groups. Patients on metformin, both alone or in combination, need monitoring and appropriate management of B12 deficiency.

Keywords

Type 2 Diabetes Mellitus (T2DM), Oral Antidiabetic Drugs (OADs), Metformin Mono Therapy, Metformin Combination Therapy, Serum B12.

Full Text:

References

Gupta, M., Singh, R. and Lehl, S. Diabetes in India: a long way to go. Int. J. Sci. Rep., 2015, 1, 1-2.

Emami-Riedmaier, A., Schaeffeler, E., Nies, A.T., Moerike, K. and Schwab, M. Stratified medicine for the use of antidiabetic medication in treatment of type II diabetes and cancer: Where do we go from here? J. Intern. Med., 2015, 277, 235-247.

Chamberlain, J.J., Rhinehart, A.S., Shaefer, C.F. and Neuman, A. Diagnosis and management of diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann. Intern. Med., 2016, 164, 542-552.

Rojas, L.B.A. and Gomes, M.B. Metformin: An old but still the best treatment for type 2 diabetes. Diabetol. Metab. Syndr., 2013, 5, 6.

Pflipsen, M.C., Oh, R.C., Saguil, A., Seehusen, D.A., Seaquist, D. and Topolski, R. The prevalence of vitamin B12 deficiency in patients with type 2 diabetes: A cross-sectional study. J. Am. Board. Fam. Med., 2009, 22, 528-534.

Wulffelé, M.G., Kooy, A. and Lehert, P. 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, 455-463.

Singh, A.K., Kumar, A., Karmakar, D. and Jha, R.K. Association of B12 deficiency and clinical neuropathy with metformin uses in type 2 diabetes patients. J. Postgraduate Med., 2013, 59, 253-257.

Kibirige, D. and Mwebaze, R. Vitamin B12 deficiency among patients with diabetes mellitus: Is routine screening and supplementation justified? J. Diabet. Metab. Disord., 2013, 12, 17.

Chacko, M. and Begum K. Eating behavior and nutrient adequacy- A prospective study in adolescent girls [dissertation]. Department of studies in Food Science and Nutrition, Manasagangotri, University of Mysore, 2004.

Carmel, R. Biomarkers of cobalamin (vitamin B12) status in the epidemiological setting: A critical overview of context, applications and performance characteristics of cobalamin, MMA and holotranscobalamin II. Am. J. Clin. Nutr., 2011, 94, 348-358.

Misra, A., Sharma, R., Gulati, S. and Joshi, S.R, Sharma V, Ghafoorunissa., Ibrahim, A., Joshi, S., Laxmaiah, A., Kurpad, A., Raj, R.K., Mohan, V., Chandalia, H., Krishnaswamy, K., Boindala, S., Gopalan, S., Bhattiprolu, S.K., Modi, S., Vikram, N.K., Makkar, B.M., Mathur, M., Dey, S., Vasudevan, S., Gupta, S.P., Puri, S., Joshi, P., Khanna, K., Mathur, P., Krishnaswamy, S., Madan, J., Karmarkar, M., Seth, V., Passi, S.J., Chadha, D. and Bhardwaj, S. Consensus dietary guidelines for healthy living and prevention of obesity, the metabolic syndrome, diabetes and related disorders in Asian Indians. Diabet. Technol. Ther., 2011, 13, 683-694.

Liu, Q., Li, S., Quan, H. and Li, J. Vitamin B12 status in metformin treated patients: systematic review. PLoS One, 2014, 9, 6.

Roy, R.P., Ghosh, K., Ghosh, M., Acharyya, A., Bhattacharya, A. and Pal, M. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Ind. J. Endocr. Metab., 2016, 20, 631-637.

Pawlak, R. Is vitamin B12 deficiency a risk factor for cardiovascular disease in vegetarians? Am. J. Prev. Med., 2015, 48, 6.

Stover, P. J. Vitamin B12 and older adults. Current Opinion in Clini. Nutri. Metabol. Care., 2010, 13, 24-27.

Villamor, E., Mora-Plazas, M., Forero, Y., Lopez-Arana, S. and Baylin A. Vitamin B12 status is associated with socio-economic level and adherence to an animal food dietary pattern in Colombian school children. J. Nutr., 2008, 138, 1391-1398.

Briani, C., Dalla Torre, C., Citton, V., Manara, R., Pompanin, S., Binotto, G. and Adami, F. Cobalamin deficiency: Clinical picture and radiological findings. Nutri., 2013, 5, 4521-4539.

Liu, K.W., Dai, L.K. and Jean, W. Metformin-related vitamin B12 deficiency. Age Agei., 2006, 35, 200-201.

Filioussi, K., Bonvoas, S. and Katsaros, T. Should we screen diabetes patients using biguanides for megaloblastic anaemia? Aust. Fam. Physici., 2004, 32, 383-384.

Raizada, N., Jyotsna, V.P., Sreenivas, V. and Tandon, N. Serum vitamin B12 levels in type 2 diabetes patients on metformin compared to those never on metformin: A cross-sectional Study. Ind. J. Endocrinol. Metabol., 2017, 21, 424-428.

Ko, S-H., Ko, S-H., Ahn, Y-B., Song, K.H., Han, K.D., Park, Y.M., Ko, S.H. and Hye-Soo Kim, H.S. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J. Korean Med. Sci., 2014, 29, 965-972.

Ting, R.Z., Szeto, C.C., Chan, M.H., Ma, K.K. and Chow, K.M. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch. Intern. Med., 2006, 166, 1975-1979.

Mahajan, S.K. and Aundhakar, S.C.A study of the prevalence of serum vitamin B12 and folic acid deficiency in Western Maharashtra. J. Family Med. Primary Care, 2015, 4, 64-68.

Pacholok, S.M. and Stuart, J.J. Could it be B12? An Epidemic of Misdiagnosis. Publisher: Quill Driver Books; 2nd edi. (January 26, 2011).


Refbacks

  • There are currently no refbacks.