SUN-693 Fasting and Postprandial DNA Methylation Signatures in Adipose Tissue From Asymptomatic Individuals With Glycemic Alterations

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Abstract Disclosure: F. Escalante-Araiza: None. A. Martínez-Hernández: None. H. García-Ortiz: None. E. Huerta-Avila: None. J. Carrillo-Ruiz: None. E. Rodriguez-Ayala: None. R. Bastarrachea: None. F. Barajas-Olmos: None. L. Orozco: None. Cardiovascular risk phenotypes of immunometabolic origin, such as dysglycemia, dyslipidemia and obesity, are major risk factors for type 2 diabetes (T2D). Despite a growing body of evidence demonstrating that certain postprandial biomarkers can predict cardiovascular risk, most metabolic studies have primarily focused on fasting state. In addition to genetic factors contributing to metabolic disease development, epigenetic mechanisms have been suggested as a significant player in metabolic dysregulation. Several studies have documented that DNA methylation changes are involved in T2D pathogenesis, however, there is limited understanding of the epigenetic dynamics of the insulin-sensitive tissues during the transition from fasting to postprandial states.In this study, we aimed to identify potential DNA methylation signatures associated with progressive glucose dysregulation phenotypes in 29 drug-naïve and asymptomatic individuals from the GEMM (Genética de las Enfermedades Metabólicas en México) family study. For the first time we compared the DNA methylation profile in fasting and postprandial states in subcutaneous adipose tissue (SAT) biopsies, previous informed consent. We identified differentially methylated CpG sites comparing cases (prediabetes [PD: n=9]; and type 2 diabetes [TD2: n=12]) and controls (C: n=8). Diagnosis for PD and T2D was carried out according to ADA criteria. We identified 4,599 DMCs between cases and controls across both prandial states. In the postprandial state, DMCs were predominantly hypermethylated in PD and T2D. Notably, we identified 130 DMCs in 99 genes that were consistent in PD and T2D, in both prandial states. KEGG pathway enrichment analysis documented that those genes participate in Insulin resistance, thermogenesis, mTOR signaling, among other relevant metabolic pathways. Additionally, we identified several differential methylated regions (DMRs) in 33 genes, such as ZNF577, VTRNA2-1, and ESR1, among others. In the postprandial state, we observed 95 DMRs (T2D =73 and PD=22) while in the fasting state, we identified 59 DMRs (T2D=32 and PD=27).In conclusion, our findings reveal that altered DNA methylation signatures in SAT across the prandial states are involved in DT2 pathogenesis, even before the onset of clinical manifestations, and discard that these epigenetic alterations are due to clinical interventions. Presentation: Sunday, July 13, 2025

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