Effect of Metformin on Glycemic Control Regarding Carriers of the SLC22A1/OCT1 (rs628031) Polymorphism and Its Interactions with Dietary Micronutrients in Type 2 Diabetes

Eloy A Zepeda-Carrillo; Omar Ramos-Lopez; Erika Martínez-López; Elisa Barrón-Cabrera; J Antonio Bernal-Pérez; Luisa E Velasco-González; Ernesto Rangel-Rios; J Fausto Bustamante Martínez; Rafael Torres-Valadez

doi:10.2147/DMSO.S354579

Effect of Metformin on Glycemic Control Regarding Carriers of the SLC22A1/OCT1 (rs628031) Polymorphism and Its Interactions with Dietary Micronutrients in Type 2 Diabetes

Diabetes Metab Syndr Obes. 2022 Jun 10:15:1771-1784. doi: 10.2147/DMSO.S354579. eCollection 2022.

Affiliations

¹ Specialized Unit in Research, Development and Innovation in Genomic Medicine, Nayarit Center for Innovation and Technology Transfer, Autonomous University of Nayarit, Tepic, Nayarit, Mexico.
² Civil Hospital "Dr. Antonio González Guevara", Health Services in Nayarit, Tepic, Nayarit, Mexico.
³ Medicine and Psychology School, Autonomous University of Baja California, Tijuana, B.C, Mexico.
⁴ Institute of Translational Nutrigenetics and Nutrigenomics, Department of Molecular and Genomic Biology, University Center of Health Sciences, University of Guadalajara, Guadalajara, Jalisco, Mexico.
⁵ Faculty of Nutrition and Gastronomy Sciences, Autonomous University of Sinaloa, Culiacan, Sinaloa, Mexico.
⁶ Family Medicine Unit No. 24 "Ignacio García Téllez", Mexican Social Security Institute, Tepic, Nayarit, Mexico.
⁷ Integral Health Academic Unit, Autonomous University of Nayarit, Tepic, Nayarit, Mexico.

^# Contributed equally.

Abstract

Purpose: Differences in metformin effect on glycemic control in type 2 Diabetes (T2D) have been associated with diet, obesity, years since T2D diagnosis and genetic factors, such as the Met408Val (rs628031) SLC22A1/OCT1 gene polymorphism. This study aimed to analyze the effect of metformin and diet on glycemic control and its association with the Met408Val polymorphism in patients with T2D from western Mexico.

Patients and methods: A total of 240 T2D adult patients were enrolled in this cross-sectional study. Anti-hyperglycemic therapy, dietary intake, body composition and glycemic profile were recorded and the determination of genotypes of SLC22A1/OCT1 gene (rs628031) was performed using an allelic discrimination assay.

Results: The type of metformin therapy was 47% monotherapy, 45% dual therapy (metformin+glibenclamide or metformin+insulin) and 8% triple therapy (metformin+glibenclamide+insulin). Individuals with metformin monotherapy had a higher glycemic control frequency (%HbA1c <7.0) compared with the dual and triple treatment schemes (77% vs 35% and 15%, respectively; p<0.001). Interestingly, a high potassium intake was documented in the three anti-hyperglycemic therapies and a lower intake of micronutrients, including calcium, magnesium, and zinc. An interaction was found between calcium intake and carriers of the risk allele A (408Val) with %HbA1c (P interaction=0.028), and potassium intake with the TyG index (P interaction=0.027). In addition, there was a positive correlation between calcium intake and %HbA1c (r=0.682; p=0.010), and potassium intake vs TyG index (r=0.593; p=0.033) in risk allele A (408Val) carriers with metformin monotherapy. Genotype frequencies were GG homozygotes (76.6%), GA heterozygotes (21.5%) and AA homozygotes (1.9%). The allele frequency was 87.4% for the ancestral allele G and 12.6% for the risk allele A.

Conclusion: These findings suggest a differing effect of metformin on glycemic control regarding calcium and potassium intake and the Met408Val SLC22A1/OCT1 gene polymorphism in T2D patients.

Keywords: SLC22A1/OCT1 gene; calcium intake; gene-nutrient interactions; nutrigenetic; pharmacogenetic; potassium intake.

Grants and funding

The laboratory infrastructure was supported by The National Council for Science and Technology (CONACyT), México (grant number: INFR-2016-01-268517) and material by The Secretary of Public Education (SEP), México (grant number: P/PFCE-2018-18MSU0019M-04). Part of this project was carried out with resources from the special tax destined to the Autonomous University of Nayarit (Article Publishing Charge) Both sources did not participate in the collection, analysis and interpretation of data; neither in the writing and/or in the decision to submit this article.