Background: Metformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by ) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated () is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in rs622342 and rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.
Methods: This cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment.
Results: Fasting plasma glucose (FPG) levels, HbA levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele ( < 0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA ( = 0.629, < 0.001) and negatively associated with Lg10 FPG ( = -0.708, < 0.001).
Conclusions: The variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.
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http://dx.doi.org/10.1155/2020/2975898 | DOI Listing |
Front Pharmacol
September 2024
Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
In Mexico, 75% of diabetes mellitus type 2 (DMT2) patients are not in glycaemic control criteria (HbA1c<7%); this entails a significantly variable drug response. Amongst the factors influencing such variability, are genetics, more specifically, single nucleotide polymorphisms (SNPs). Three genes implied in metformin pharmacokinetics are , , and , which are polymorphic.
View Article and Find Full Text PDFPharmacogenomics J
October 2024
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Biomed Rep
August 2024
Department of Pharmacology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico.
Type 2 diabetes mellitus (T2DM) is a major global health problem. Response to first-line therapy is variable. This is partially due to interindividual variability across those genes codifying transport, metabolising, and drug activation proteins involved in first-line pharmacological treatment.
View Article and Find Full Text PDFSci Rep
March 2024
Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis, Tunisia.
Curr Diabetes Rev
May 2024
Medical Faculty, Duta Wacana Christian University, Yogyakarta, Indonesia.
Background: Solute Carrier Family 22 Member 1 (, also known as OCT1) protein has a vital role in the metabolism of metformin, a first-line anti-diabetes medication. Genetic poly-morphism in influences individual response to metformin.
Objective: This review aims to compile the current knowledge about the effects of genetic polymorphism on metformin pharmacokinetics and HbA1c levels.
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