Abstract
Background: Vitamin B12 (cobalamin) is an essential micronutrient necessary for DNA methylation and plays role in lipid metabolic reactions. Metformin is the first therapeutic choice for T2DM management. Prolonged use of metformin causes vitamin B12 deficiency due to poor absorption by interfering with calcium-based vitamin B12 absorption. Vitamin B12 deficiency leads to elevated homocysteine levels. The aim of this study was to evaluate serum vitamin B12 and homocysteine levels in type 2 diabetic patients with and without metformin therapy. Methods: A cross-sectional study was conducted on two hundred and thirty diabetic patients (180 males and 50 females). Their ages ranged from (30 - 60 years) living in Saudia Arabia at Al-Madinah Al-Monawarah. Patients were selected at outpatients clinics of Islamic University Medical Center during follow up at internal medicine and endocrinology clinic. The included patients were diagnosed with type 2 diabetes mellitus according to American Diabetes Association (ADA) Criteria. The included patients were categorized into two groups according to treatment with metformin drug. Laboratory measurements included serum level of vitamin B12, serum total homocysteine, serum fasting glucose and serum folate. Blood EDTA samples were used to measure HbA1c and MCV. Neurological examinations were performed to detect presence of peripheral neuropathy using Toronto Clinical Neuropathy Score (TCSS), which is a validated and reliable scale for the diagnosis and staging of diabetic polyneuropathy. Results: There were no statistical differences between the two groups as regard (age, sex, smoking, weight, BMI, systolic blood pressure, diastolic blood pressure, fasting blood glucose, Folate and MCV). There were statistical differences between the two groups as regard (duration of diabetes, duration of metformin therapy, dose of metformin, Serum homocystein and HbA1c). The mean of vitamin B12 (pg/mL) of group 1 (312.65 ± 92.28) was lower than that of group 2 (381.55 ± 88.04). In group 1 number of patients with normal vitamin B12 was 116 out of 150 (77.3%) and number of patients with deficient vitamin B12 was 34 out of 150 (22.7%). In group 2 number of patients with normal vitamin B12 was 72 out of 80 (90%) and number of patients with deficient vitamin B12 was 8 out of 80 (10%). Regarding neuropathy; in group 1 113 patients (75.3%) had no neuropathy, 24 patients (16%) had mild neuropathy and 13 patients (8.7%) had moderate neuropathy. In group 2, 71 patients (88.8%) had no neuropathy, 7 patients (8.7%) had mild neuropathy and 2 patients (2.5%) had moderate neuropathy. In conclusion, in our study, the prevalence of vitamin B12 deficiency was higher in metformin users than in non-metformin users. There was an association between vitamin B12 deficiency and the dose and duration of metformin use. There was also an increase in homocysteine level due to vitamin B12 deficiency. Therefore, we recommend routine screening for serum vitamin B12 and homocysteine in individuals with T2DM who take daily metformin doses higher than 2000 mg, or for a duration exceeding 4 years.
Highlights
Vitamin B12 is an essential micronutrient necessary for DNA methylation and plays role in lipid metabolic reactions
Metformin induced deficiency of vitamin B12 presenting as peripheral neuropathy may be mistaken for diabetic neuropathy [16]
The included patients were diagnosed with type 2 diabetes mellitus according to American Diabetes Association (ADA) Criteria [HbA1C ≥ 6.5%, FPG ≥ 126 mg/dl, 2-h plasma glucose ≥200 mg/dl, In a patient with classic symptoms of hyperglycemia, a random plasma glucose ≥200 mg/dl] [23]
Summary
Vitamin B12 (cobalamin) is an essential micronutrient necessary for DNA methylation and plays role in lipid metabolic reactions. Metformin induced deficiency of vitamin B12 presenting as peripheral neuropathy may be mistaken for diabetic neuropathy [16]. Homocysteine (Hcy) is a risk factor strongly associated with cardiovascular complications in T2DM. The aim of this study was to evaluate serum vitamin B12 and homocysteine levels in type 2 diabetic patients with and without metformin therapy. Methods: A cross-sectional study was conducted on two hundred and thirty diabetic patients (180 males and 50 females). Their ages ranged from (30 - 60 years) living in Saudia Arabia at Al-Madinah Al-Monawarah. Laboratory measurements included serum level of vitamin B12, serum total homocysteine, serum fasting glucose and serum folate. The mean of vitamin B12 (pg/mL) of group 1 (312.65 ± 92.28) was lower than that of group 2
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