Hassna OSAMA, Hoda Abd Elbadie HUSSEİN, Mohamed E. ABDELRAHİM, Heba F SALEM

Screening the Effect of Metformin on Serum Vitamin B12 and Blood Homocysteine Levels in Patients with Type 2 Diabetes Mellitus

Vitamin B12 deficiency is a side effect of metformin use in patientswith type 2 diabetes mellitus (T2DM) and associated with increase in plasma homocysteine levels.The aim of present work was to screen vitamin B12 and homocysteine levels in patients with T2DM on metformin therapy. Patients with T2DM collected from Fayoum University hospital outpatient clinics were screened and divided into three groups. Group 1 was thirty patients on metformin therapy for more than one year without vitamin B12 supplementation; group 2 was thirty patients on metformin therapy for more than one year on vitamin B12 supplementation and group 3 was patients not receiving metformin therapy (control group). All patients were subjected to complete history taking, including peripheral neuropathy and laboratory investigations. The mean±SD serum vitamin B12 level was significantly higher in the metformin and vitamin B12 supplementation users compared to metforminonly and nonmetformin users (p

PDF

___

1. Zhang Y, Xie Y, Meng D, Zhang H, Chen H, Liu E. Clinical study of treatment switching from premixed insulin to basal insulin combined with oral hypoglycemic drugs in patients with type 2 diabetes. Diabetol Metab Syndr. 2014;6(1):37.

2. Garber A, Klein E, Bruce S, Sankoh S, Mohideen P. “Metformin-glibenclamide versus metformin plus rosiglitazone in patients with type 2 diabetes inadequately controlled on metformin monotherapy”. Diabetes Obes Metab. 2006;8(2):156-63.

3. Prato S, Lebovitz H. Pharmacological Treatment of Type 2 Diabetes: Advantages and Dilemmas. Transl Endocrinol Metab. 2014;(3)2:27.

4. Derosa G1, Mugellini A, Ciccarelli L, Crescenzi G, Fogari R. Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin. Diabetes Res Clin Pract. 2003;60(3):161-9.

5. 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.

6. Pflipsen MC, Oh RC, Saguil A, Seehusen DA, 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(5):528-34.

7. Hermann L, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. Br J Diabetes Vasc Dis. 2004;4(6):401-406.

8. Nervo M, Lubini A, Raimundo F. Vitamin B12 in metformin-treated diabetic patients: a cross-sectional study in Brazil. Rev Assoc Med Bras. 2011;57(1):46-9.

9. Liu K, Dai L, Jean W. Metformin-related vitamin B12 deficiency. Age Ageing. 2006;35(2):200-1.

10. Bell D. Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy. South Med J. 2010;103(3):265-7.

11. Kumthekar A, Gidwani H, Kumthekar A. Metformin Associated B12 Deficiency. J Assoc Physicians India. 2012;60:58-60.

12. Reinstatler L, Qi Y, Williamson R, Garn J, Oakley-Jr G. 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.

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

14. Chan Chee Wun Joyce, Chan Hoi Yan Florence, Wong Ho Nam Howard, Yeung Chun Yip. Characteristics of Vitamin B12 Deficiency in Adult Chinese Patients with Type 2 Diabetes and the Implication of Metformin, Topics in the Prevention, Treatment and Complications of Type 2 Diabetes, Prof. Mark Zimering, ed, 2011. Available from: http://www.intechopen.com/books/topics-in-the-prevention-treatment-and-complicationsof-type-2-diabetes/characteristics-of-vitamin-b12-deficiency-in-adult-chinese-patientswith-type-2-diabetes-and-the-imp access date 01.07.2015

15. Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJ, Stehouwer CD. 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 Int Med. 2003;254(5):455-63.

16. Marar O, Senturk S, Agha A, Thompson C, Smith D. The prevalence of vitamin B12 deficiency in T2DM on metformin. RCSIsmj. 2011;4(1):16-20.

17. Sato Y, Ouchi K, Funase Y, Yamauchi K, Aizawa T. Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes. Endocr J. 2013;60(12):1275-80.

18. Nervo M, Lubini A, Raimundo FV. Vitamin B12 in metformin-treated diabetic patients: a cross sectional study in Brazil. Rev Assoc Med Bras. 2011;57(1):46-9.

19. De Groot-Kamphuis DM, van Dijk PR, Groenier KH, Houweling ST, Bilo HJ, Kleefstra N. Vitamin B12 deficiency and the lack of its Consequences in type 2 diabetes patients using Metformin. NETH J MED. 2013;71(7):386-90.

20. Shtaynberg N, Singh M, Sohn P, Goldman M, Cohen N. Methylmalonic acid as an indicator of vitamin B12 deficiency in patients on metformin. J Diabetes Mellitus. 2012;2(1):72-5.

21. 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.

22. Ting R, Szeto C, Chan M, Ma K, Chow K. Risk factors of vitamin B (12) deficiency in patients receiving metformin. Arch Internal Med. 2006;166(18):1975-9.

23. Kos E, Liszek M, Emanuele M, Durazo-Arvizu R, Camacho P. The effect of metformin therapy on vitamin D and B12 levels in patients with diabetes mellitus type 2. Endocr Pract. 2012;18(2):179-84.

24. 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:c2181.

25. Hoogeveen EK, Kostense PJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CDA. Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus? J Intern Med. 1997;242(5):389-94.

26. 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.

27. 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.

28. Ko SH, Ko SH, Ahn YB, Song KH, Han KD, Park YM, Ko SH, Kim HS. Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes. J Korean Med Sci. 2014;29(7):965-72.

29. Ajabnoor MA, AL-Ama MN, Banjar Z, Rafee AA, Sheweita SA. Homocysteine and cardiovascular disease in diabetic patients. Med Sci Monit. 2003;9(12):CR523-7.

30. Abraham R, John MJ, Calton R, Dhanoa J. Raised serum homocysteine levels in patients of coronary artery disease and the effect of vitamin B12 and folate on its concentration. Indian J Clin Biochem. 2006;21(1):95-100.

31. Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about? Swiss Med Wkly. 2006;136(47-48):745-56.

32. Mohammadi M, Amini M, Aminiorroay A, Rezvanian H, Kachuei A, Siyavash M, Soodabeh- Rahimi Saghand SR Afkhami-Ardekani M. Effect of metformin and folic acid on plasma homocysteine level in type 2 diabetic patients. Int J Med Sci. 2009;1(3):88-90.