Analysis of risk factors for vitamin B12 deficiency in patients with type 2 diabetes mellitus and its relation to the use of metformin

Background. The use of metformin has been associated with vitamin B12 deficiency in patients with type 2 diabetes mellitus. Objective. The present study evaluates the relationship between vitamin B12 deficiency and its risk factors. Moreover, it investigates the relationship between established deficiency and clinically detectable periph­eral neuropathy. Material and methods. A cross-sectional study involving patients with type 2 diabetes mellitus who were assisted at a public health care service, which is a reference center in Diabetes. Peripheral neuropathy was detected by Neuropathy Symptom Score, Vibration Sensitivity Test, Achilles Reflex and Monofilament Test. Vitamin B12 levels were determined by means of two laboratory measurements. Results. The study included 316 subjects, from which 91% were metformin users. Vitamin B12 deficiency was observed in 14% of participants in the study. All patients with vitamin B12 deficiency used metformin, with an odds ratio of 2.6 for those using doses higher than 1000 mg/day (95% confidence interval: 1.3–5.3, p = 0.009). Vitamin B12 deficiency was also statisti­cally related to the use of angiotensin-converting enzyme inhibitors (p = 0.02). Peripheral neuropathy was observed in 41% of patients and was not related to vitamin B12 deficiency. The prevalence of peripheral neuropathy was lower among metformin users (39% vs. 60%; p = 0.04). Conclusions. This study demonstrated a dose-depend­ent association between metformin use and vitamin B12 deficiency, in addition to an association with the use of angiotensin-converting enzyme inhibitors. In contrast, Vitamin B12 deficiency was not related to clinically detected neuropathy.