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

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:

• nutrigenetic
• pharmacogenetic
• SLC22A1/OCT1 gene
• gene-nutrient interactions
• calcium intake
• potassium intake

Acknowledgments

The authors express their gratitude to participants of this cohort study for their enthusiastic support and the staff of Family Medicine Unit No. 24 of Mexican Institute of Social Security for their valuable help. We acknowledge students in Nutrition Luis Roberto Mejia Godoy and Ivette Xitlalli Eleuterio Salvador, as well as Pharmaceutical Chemists Fabiola B. Moreno Escalera, Kevin J, Frías Delgadillo and Sara A. Campos Huerta for their support in obtaining data of all patients in this study.

To the Interinstitutional Program for the Strengthening of Research and Graduate Studies of the Pacific (Dolphin Program) for promoting the collegiate work that led to the creation of the Dolphin Research Networks within the mobility subprogram of professors and researchers.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

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.