Vitamin B-12 deficiency associated with metformin treatment of type 2 diabetes mellitus in daily practice: Clinical consequences
E. Jungmann, J. Bolle, C. Schmitz & G. Jungmann
In a recent study, vitamin B-12 deficiency was observed in 10% of metformin-treated type 2 diabetic patients, but neurological status of the patients was not defined. Thus, potential consequences of this observation remained subject to controversy. Therefore, we decided to examine to which extent a vitamin B-12 deficiency can be detected in metformin-treated diabetic patients in daily practice and which impact vitamin B-12 deficiency if present could have on the development of diabetic neuropathy in these patients.
88 consecutive type 2 diabetic patients with metformin treatment for >1 year (37 females, 51 males, age, 66±2 years [SEM], duration of diabetes, 10±2 years, metformin, 1450±120 mg/day for 6±2 years) were included in this cross-sectional study. We measured vitamin B-12 levels, folate, 25-OH-vitamin D and PTH by enzyme immunoassay, additionally we performed a routine screening of all patients for signs or symptoms of diabetic neuropathy.
10% of the patients had vitamin B-12 deficiency, a total of 29% of the patients had vitamin B-12 levels<200 pmol/l. Patients with decreased vitamin B-12 levels received higher doses of metformin for longer duration than patients with vitamin B-12 levels >200 pmol/l (P<0.05). Moreover, they exhibited an increased prevalence of diabetic neuropathy, had decreased folate levels and decreased vitamin D levels (P<0.05). In patients with decreased vitamin B-12, diabetic neuropathy developed after shorter duration of diabetes and despite better HbA1c levels than in patients with normal vitamin B-12 (P<0.05).
In this cross-sectional study in daily practice, there is evidence for neurological consequences of metformin-associated vitamin B-12 deficiency, which therefore must be considered as eventually harmful for metformin-treated patients. Thus, patients should be regularly screened and vitamin B-12 replacement started as early as necessary, together with the replacement therapy of mostly associated vitamin D-deficiency.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.