Epigenetic changes associated with hyperglycaemia exposure in the longitudinal DESIR cohort

Aim: - Understanding DNA methylation dynamics associated with progressive hyperglycaemia exposure could provide early diagnostic biomarkers and an avenue for delaying type 2 diabetes mellitus (T2DM). We aimed to identify DNA methylation changes during a 6-year period associated with early hyperglycaemia exposure using the longitudinal D.E.S.I.R. cohort. Methods: - We selected individuals with progressive hyperglycaemia exposure based on T2DM diagnostic criteria: 27 with long-term exposure, 34 with short-term exposure and 34 normoglycaemic controls. DNA from blood at inclusion and at the 6-year visit was subjected to methylation analysis using 850K methylation-EPIC arrays. A linear mixed model was used to perform an epigenome-wide association study (EWAS) and identify methylated changes associated with hyperglycaemia exposure during a 6-year time-period. Results: - We did not identify differentially methylated sites that reached false discovery rate (FDR)-significance in our cohort. Based on EWAS, we focused our analysis on methylation sites that had a constant effect during the 6 years across the hyperglycaemia groups compared to controls and found the most statistically significant site was the reported cg19693031 probe (TXNIP). We also performed an EWAS with HbAlc, using the inclusion and the 6-year methylation data and did not identify any FDR-significant CpGs. Conclusions: - Our study reveals that DNA methylation changes are not robustly associated with hyperglycaemia exposure or HbAlc during a short-term period, however, our top loci indicate potential interest and should be replicated in larger cohorts. (C) 2022 Elsevier Masson SAS. All rights reserved.

Automated summary

This study examines the relationship between DNA methylation and hyperglycaemia exposure, as well as type 2 diabetes mellitus, over a 6-year period. Methylation analysis was conducted on individuals with long-term and short-term hyperglycaemia exposure, and potential methylation sites were identified.