|
Sign In to gain access to subscriptions and/or personal tools.
|
Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study
Leif Sparre Hermann
Diabetes Unit, Medical Department, Uddevalla Hospital, Uddevalla, Sweden, hermannbjornstad{at}wanadoo.fr
BO Nilsson
Department of Clinical Chemistry, Uddevalla Hospital, Uddevalla, Sweden
Staffan Wettre
Diabetes Unit, Medical Department, Uddevalla Hospital, Uddevalla, Sweden
Aim
To assess the vitamin B12 status of patients with type 2diabetes who had been receiving metformin treatment for at least one year.
Methods
Patients with type 2 diabetes attending a diabetes clinic were included in a cross-sectional cohort study. Patients exposed to metformin for more than one year (n=53) were compared with a non-exposed control group (n=31). Serum cobalamin and other variables reflecting vitamin B12 status were measured.
Results
Patients on metformin had lower cobalamin (289±137 vs. 395±162 pmol/L; p<0.01) and holotranscobalamin (76±49 vs. 97±41 pmol/L; p<0.05), and higher HCy (11.3+3.3 vs. 10.3±2.3 µmol/L; p<0.05); these changes were correlated. Eight metformin patients, but no controls, had holotranscobalamin below the normal range (p<0.05). Methylmalonic acid and folate were similar in both groups.
Conclusion Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency. Our results highlight the necessity of checking B12 status during metformin therapy.
Key Words: metformin type 2 diabetes vitamin B12.
References
- UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS-34). Lancet 1998;352:854-65.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Howlett HC, Bailey CJ A risk-benefit assessment of metformin in type 2diabetes mellitus. Drug Safety 1999;20:489-503.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Tomkin GH, Hadden DR, Weaver JA, Montgomery DA Vitamin-B12 status of patients on long-term metformin therapy. BMJ 1971;2:685-7.[Abstract/Free Full Text]
- Adams JF, Clark JS, Ireland JT et al. Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. Diabetologia 1983;24:16-18.[Web of Science][Medline]
[Order article via Infotrieve]
- DeFronzo RA, Goodman A., Metformin Investigator Group. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med 1995;333:541-9.[Abstract/Free Full Text]
- Wulffelé MG, Kooy A., Lehert P. 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;254:455-63.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Carlsen SM, Følling I., Grill V. et al. Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Scand J Clin Lab Invest 1997;57:521-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Desouza C., Keebler M., McNamara DB, Fonseca V. Drugs affecting homocysteine metabolism. Impact on cardiovascular risk. Drugs 2002;62:605-16.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Callaghan TS, Hadden DR, Tomkin GH Megaloblastic anaemia due to vitamin B12 malabsorption associated with long-term metformin treatment. BMJ 1980;280:1214-15.[Free Full Text]
- Andrès E., Noel E., Goichot B. Metformin-associated vitamin B12 deficiency. Arch Intern Med 2002;162:2251-2.[Free Full Text]
- Filioussi K., Bonovas S., Katsaros T. Should we screen diabetic patients using biguanides for megaloblastic anaemia? Austr Fam Phys 2003; 32:383-4.[Medline]
[Order article via Infotrieve]
- Hermann LS, Kalén J., Katzman P. et al. Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients. Diabetes Obes Metab 2001;3:428-34.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bauman WA, Shaw S., Jayatilleke E. et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227-31.[Abstract/Free Full Text]
- Wolever TM, Assiff L., Basu T. et al. Miglitol, an alfa-glucosidase inhibitor, prevents the metformin-induced fall in serum folate and vitamin B12 in subjects with type 2 diabetes. Nutrition Research 2000;20:1447-56.[Web of Science]
- Bagree R., Gibby OM, Penney MD, Lloyd HH Prevalence of vit.B12 deficiency with metformin treatment. Diabetic Med 1999;16(suppl 1):P61.
- Hoogeveen EK, Kostense PJ, Jakobs C. et al. Does metformin increase the serum total homocysteine level in non-insulin-dependent diabetes mellitus? J Intern Med 1997;242:389-94.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Smulders YM, Rakic M., Slaats EH et al. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999;22:125-32.[Abstract/Free Full Text]
- Nilsson-Ehle H. Age-related changes in cobalamin (vitamin B12) handling. Drugs & Aging 1998;12:277-92.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wiernsperger N. Metformin: Intrinsic vasculoprotective properties. Diabetes Technol Ther 2000;2:259-72.[CrossRef][Medline]
[Order article via Infotrieve]
- Caspary WF Biguanides and intestinal absorptive function. Acta HepatoGastroenterol 1977;24:473-80.
- Andrès E., Perrin A-E., Demangeat C. et al. The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. Eur J Intern Med 2003;14:221-6.[CrossRef][Medline]
[Order article via Infotrieve]
- Aarsand AK, Carlsen SM Folate administration reduces circulating homocysteine levels in NIDDM patients on long-term metformin treatment. J Intern Med 1998;244:169-74.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
The British Journal of Diabetes & Vascular Disease, Vol. 4, No. 6,
401-406 (2004)
DOI: 10.1177/14746514040040060701

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. C. Pflipsen, R. C. Oh, A. Saguil, D. A. Seehusen, and R. Topolski
The Prevalence of Vitamin B12 Deficiency in Patients with Type 2 Diabetes: A Cross-Sectional Study
J Am Board Fam Med,
September 1, 2009;
22(5):
528 - 534.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|