Serum B12 Levels in Type II Diabetics on Metformin Therapy and its association with Clinical Neuropathy

Holay MP, Vyawahare M, Shekar K

Abstract


Background: Metformin use in type II DM has also been known to cause B12 deficiency in as reported many studies. Iatrogenic neuropathy caused by Metformin induced B12 deficiency can add to burden of peripheral neuropathy that already exists in diabetic patients.

Aims and Objectives: 1)To determine the serum vitamin B12 levels in patients of type II DM on metformin therapy and compare it with those not on metformin therapy; 2) To correlate serum vitamin B12 levels with dose and duration of metformin therapy; 3) To investigate association between peripheral neuropathy and serum vitamin B12 levels.

Method: The present two year hospital based cross sectional study enrolled total 132 cases of type 2 diabetes mellitus and divided into two groups, (“metformin” group 70 and “non-metformin” group 62). Serum vitamin B12 levels were measured in all patients. Toronto clinical scoring system (TCSS) and nerve conduction velocity (NCV) tests were used to assess peripheral neuropathy. The correlations of vitamin B12 levels with Toronto clinical score, nerve conduction studies, cumulative dose and duration of metformin therapy was done.

Results: The serum vitamin B12 levels were significantly lower in patients who consumed metformin (292.64 ± 152.82 pg/ml) as compared to non-metformin, (406.91 ± 126.59 pg/ml) group. There was a significant negative correlation of serum vitamin B12 levels with cumulative dose and duration of metformin therapy. The incidence of neuropathy by TCSS and NCV test was significantly higher in metformin group with a positive correlation with cumulative dose and duration of metformin and a negative correlation with serum vitamin B12 levels.

Conclusion: Metformin use is significantly associated with decrease in vitamin B12 levels and increased incidence of neuropathy, this is dependent on dose and duration of metformin therapy.


Keywords


Metformin, Vitamin B12, Diabetes mellitus (DM), Peripheral neuropathy, Toronto clinical scoring system (TCSS), Nerve conduction velocity (NCV)

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References


. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA. 1995; 274(13):1049-57.

. Nygård O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J of Med. 1997; 337(4):230-7.

. Welch GN, Homocysteine LJ. Homocyst (e) ine and Atherothrombosis. N Engl J Med. 1998; 1998(338):1042-50.

. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP. 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.

. De Jager J, Kooy A, Lehert P, Wulffelé MG, Van der Kolk J, Bets D, Verburg J, Donker AJ, Stehouwer CD. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010; 340:2181-7.

. Liu KW, Dai DL, Ho W, Lau E, Woo J. Metformin-associated vitamin B12 deficiency in the elderly. Asian J Gerontol Geriatr. 2011; 6:82-7.

. Chen S, Lansdown AJ, Moat SJ, Ellis R, Goringe A, Dunstan FD, Rees JA. An observational study of the effect of metformin on B12 status and peripheral neuropathy. The British Journal of Diabetes and Vascular Disease. 2012; 12(4):189-93.

. Bauman WA, Shaw S, Jayatilleke E, Spungen AM et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes care 2000; 23(9):1227-31.

. Carlsen SM, Følling I, Grill V, Bjerve KS, Schneede J, Refsum H. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Scandinavian Journal of Clinical and Laboratory Investigation. 1997; 57(6):521-7.

. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. New England Journal of Medicine. 1995; 333(9):541-9.

. Mahajan R, Gupta K. Revisiting metformin: annual vitamin B12 supplementation may become mandatory with long-term metformin use. Journal of Young Pharmacists. 2010; 2(4):428-9.

. Singh AK, Kumar A, Karmakar D, Jha RK. Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients. Journal of Postgraduate Medicine. 2013; 59(4):253.

. Pflipsen MC, Oh RC, Saguil A, Seehusen DA, Seaquist D, Topolski R. The prevalence of vitamin B12 deficiency in patients with type 2 diabetes: a cross-sectional study. The Journal of the American Board of Family Medicine. 2009; 22(5):528-34.

. Hermann LS, Nilsson BO, Wettre S. Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. The British Journal of Diabetes and Vascular Disease. 2004; 4(6):401-6.

. Iftikhar R, Qadir A, Iqbal Z, Usman H. Prevalence of Vitamin B12 deficiency in patients of type 2 diabetes mellitus on metformin: A case control study from Pakistan. Pan African Medical Journal. 2013; 16:67.

. Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B12 deficiency in patients receiving metformin. Archives of Internal Medicine 2006; 166(18):1975-9.

. Qureshi SA, Ainsworth A, Winocour PH. Metformin therapy and assessment for vitamin B12 deficiency: is it necessary? Practical Diabetes 2011; 28(7):302-4.

. Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care. 2010; 33(1):156-61.

. Chen S, Lansdown AJ, Moat SJ, Ellis R, Goringe A, Dunstan FD, Rees JA. An observational study of the effect of metformin on B12 status and peripheral neuropathy. The British Journal of Diabetes and Vascular Disease. 2012; 12(4):189-93.

. Roy RP, Ghosh K, Ghosh M, Acharyya A, Bhattacharya A, Pal M, Chakraborty S, Sengupta N. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian Journal of Endocrinology and Metabolism. 2016; 20(5):631.




DOI: http://dx.doi.org/10.7439/ijbar.v8i8.4356

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