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

Abstract

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.