Abstract

ABSTRACTIntroduction: Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients. However, metformin induces vitamin B12 malabsorption which may increase the risk of vitamin B12 deficiency among T2DM patients. We determined the prevalence of vitamin B12 deficiency and related risk factors among Ghanaian T2DM patients on metformin therapy.Methods: This cross-sectional study recruited 196 T2DM patients attending the outpatient diabetic clinic at the Effia Nkwanta Regional Hospital, Ghana. Fasting venous blood was collected for biochemical analysis. Vitamin B12 deficiency was defined as serum B12 <100 pg/ml and methylmalonic acid (MMA) ≥ 0.4µmol/L.Results: The prevalence of vitamin B12 deficiency based on serum vitamin B12, MMA, and the combination of both methods were 32.1%, 14.8%, and 14.3%, respectively. Longer duration of metformin use [5-9 years; aOR= 2.83, 95% CI (1.03-7.81), p=0.045 and ≥10 years; aOR= 4.17, 95% CI (1.41-12.33), p=0.010], higher daily dose of metformin [1000-2000 mg/day; aOR= 1.34, 95% CI (0.25-2.74), p=0.038 and >2000 mg/day; aOR= 1.13, 95% CI (0.39-2.97), p=0.047], and very high body fat [aOR= 2.98, 95% CI (1.47-6.05), p=0.020] were significantly associated with increased odds of vitamin B12 deficiency. For daily dose of metformin, a cutoff value of 1500 mg/day presented with a sensitivity, specificity, and AUC of 71.4%, 40.1%, and 0.54 (95% CI, 0.53-0.54), respectively, in predicting vitamin B12 deficiency. A ≥ six (6) years duration of metformin therapy presented with a sensitivity, specificity, and AUC of 70.4%, 62.9%, and 0.66 (95% CI, 0.57-0.75), respectively, in predicting vitamin B12 deficiency.Conclusion: Vitamin B12 deficiency is high among T2DM patients on metformin therapy in Ghana. There is the need for regular monitoring of vitamin B12 levels especially in T2DM patients on metformin daily dose of ≥ 1500 mg for duration of therapy ≥ 6 years.

Highlights

  • Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients

  • The prevalence of vitamin B12 deficiency based on serum vitamin B12, methylmalonic acid (MMA), and the combination of both methods were 63/196 (32.1%), 29/196 (14.8%), and 28/196 (14.3%), respectively (Figure 2)

  • The prevalence of vitamin B12 deficiency based on serum vitamin B12, MMA, and the combination of both methods was 32.1%, 14.8%, and 14.3%, respectively

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Summary

Introduction

Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients. Metformin induces vitamin B12 malabsorption which may increase the risk of vitamin B12 deficiency among T2DM patients. We determined the prevalence of vitamin B12 deficiency and related risk factors among Ghanaian T2DM patients on metformin therapy. Reports indicated that metformin improves peripheral insulin sensitivity and reduces the risk of cardiovascular mortality in T2DM [7,8] in addition to its beneficial effects on weight loss and vascular protection [9]. As with most medications, the use of metformin present with some side effects. Though most of these side effects are mild, reports indicate that metformin use is associated with the diminution of the terminal iliac uptake of vitamin B12 [10,11]. Metformin-induced Vitamin B12 deficiency has been reported to be duration of therapyand dose-dependent [12]

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