The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin

- The loss-of-function variant OCT2-T201M contributes to changes in insulin resistance.
- The variant OCT2-T201M influences the glucose-lowering effects of metformin.
- Gender as an independent variable has a significant relationship with HOMA-BCF.
- The interaction of the variant OCT2-T201M and BMI affect HOMA-IR.

AimsInsulin resistance is characterized by impaired biological response of peripheral tissues to the metabolic effects of insulin. Organic cation transporter 2 (OCT2) is responsible for 80% metformin clearance. Limited information is available on the potential relationship between genetic variants of OCT2 and insulin resistance. In this study, we examined the role of OCT2-T201M (602 C>T) variant in insulin resistance in patients with type 2 diabetes (T2D) who were treated with metformin.MethodsSerum concentrations of insulin and C-peptide were assessed using ELISA. Homeostasis model assessment for insulin resistance (HOMA-IR) and HOMA for beta cell function (HOMA-BCF) were determined. PCR-based restriction fragment length polymorphism was used to genotype the OCT2-T201M variant.ResultsPatients with minor alleles had higher HbA1c concentrations (p = 0.019), fasting glucose levels (p = 0.023), HOMA-IR (p = 0.03), and HOMA-BCF (p = 0.26) than patients with common alleles. Multivariate analysis identified a significant association between the variables OCT2-T201M and gender, with HOMA-IR and HOMA-BCF (Wilks' λ = 0.549, F = 12.71, p < 0.001 for OCT2-T201M and Wilks' λ = 0.369, F = 26.46, p < 0.001 for gender. Changes in HOMA-BCF were inversely correlated with changes in fasting glucose levels (r = −0.412, p = 0.008) and HbA1c (r = −0.257, p = 0.114).ConclusionsOur findings suggest that the loss-of-function variant OCT2-T201M (rs145450955) contribute to changes in insulin resistance and beta cell activity in patients with T2D treated with metformin. Moreover, gender as an independent variable has a significant relationship with HOMA-BCF.