Vitamin B12 deficiency in long-term metformin treated type 2 diabetic patients: Prevalence and risk factors in a Tunisian population

Objectives: To determine the prevalence of vitamin B12 deficiency in a Tunisian population with type 2 diabetes (T2D) on metformin treatment for more than three years and to identify its risk factors. Methods: This is a cross-sectional study conducted on 257 patients with T2D treated with metformin for at least three years. Patients were divided into two groups according to their vitamin B12 status. Low vitamin B12 was defined as ≤ 203 pg/mL. Results: The mean age of the patients was 59.8 ± 7.9 years. The mean duration of metformin use was 10.2 ± 5.2 years. The mean vitamin B12 level was 294.9 ± 156.4 pg/mL. The prevalence of vitamin B12 deficiency was 28.4%. Male gender, HbA1c < 7% and hyperhomocysteinemia were significantly associated with vitamin B12 deficiency (respectively p = 0.02, p < 0.001, p < 0.001). Homocysteine level was negatively correlated with vitamin B12 level ( r = −0.2, p = 0.001). Dose and duration of metformin treatment, peripheral neuropathy and anemia were not associated with vitamin B12 deficiency. On multivariate analysis, HbA1c < 7% and hyperhomocysteinemia were independently associated with vitamin B12 deficiency (respectively OR = 3.2, 95%CI = [1.6–6.3] and OR = 2.3, 95%CI = [1.2–4.2]). Discussion: The prevalence of vitamin B12 deficiency in patients with T2D on metformin treatment was high. Hyperhomocysteinemia is associated with vitamin B12 deficiency suggesting that the deficit occurs at the tissue level.