METFORMIN’S IMPACT ON EPIGENETIC AGING IN MOTHERS WITH GESTATIONAL DIABETES

Abstract

Introduction: Gestational diabetes mellitus (GDM) is the most common medical complication in pregnancy. It is associated with hastened cellular aging and accelerated epigenetic aging, with an average of 5 years increase in epigenetic age in GDM cohorts. Metformin, a caloric restriction mimic, is expected to modulate DNA methylation signatures to mitigate GDM-induced age-related epigenetic changes. Objectives: The aim of the study was to evaluate differential methylation and biological age clocks across metformin-treated versus lifestyle-modified diet exposures in GDM patients. Methods: This study is a single-center observational study in Qatar. Females with confirmed diagnosis of GDM were recruited to metformin treatment (cases) or lifestyle-modified diets (controls). DNA was extracted using FlexiGene DNA kit followed by quantitative and qualitative validation of DNA sample integrity. DNA methylation profiling was conducted using the Infinium Methylation EPIC v2.0 BeadChip Kit. Data analysis was conducted using R software. Subsequently, functional pathway analysis was done using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: A total of 36 patients were recruited, with 10 cases and 26 controls. There were no significant differences in FDR-adjusted p-value for metformin-treated GDM cohorts in site-specific and regional differential methylation. Functional pathways elucidated new signaling pathways that need to be studied and validated. No significance in biological age was observed across Horvath, Hannum, PhenoAge, and GrimAge-2 clocks. Conclusion: In GDM patients on metformin, there is no difference in DNA methylation pattern or epigenetic aging acceleration compared to lifestyle modifications.

Date of Award	2025
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences