Vitamin B-12 deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

Introduction: 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 \u3c 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 \u3e 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

Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines

The intracellular penetration of darunavir, a second-generation HIV protease inhibitor, is limited by the activity of the efflux P-glycoprotein (ABCB1). ABCB1 expression and/or activity levels can vary between individuals due to genetic polymorphisms including the c.1199G>A, c.1236C>T, c.2677G>T and c.3435C>T variants, which could in part explain why the pharmacokinetics of darunavir are so variable from one individual to another. While a few clinical studies have failed to demonstrate an influence of these polymorphisms on darunavir pharmacokinetics, drug-drug interactions and methodological limitations may have prevented them from revealing the true influence of ABCB1 variants. In this work, we report on the intracellular accumulation of darunavir in recombinant HEK293 cell lines expressing wild-type ABCB1 or one of several variants: ABCB1 1199A, ABCB1 3435T, and ABCB1 1236T/2677T/3435T. We demonstrate that while ABCB1 expression limits intracellular accumulation of darunavir, there is no significant difference in efflux activity between cells expressing wild-type ABCB1 and those that express any of the studied variant