PMID- 35427775
OWN - NLM
STAT- MEDLINE
DCOM- 20220802
LR  - 20221207
IS  - 1878-1780 (Electronic)
IS  - 1262-3636 (Linking)
VI  - 48
IP  - 4
DP  - 2022 Jul
TI  - Epigenetic changes associated with hyperglycaemia exposure in the longitudinal 
      D.E.S.I.R. cohort.
PG  - 101347
LID - S1262-3636(22)00030-1 [pii]
LID - 10.1016/j.diabet.2022.101347 [doi]
AB  - 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. 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 HbA1c, 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 HbA1c during a short-term period, however, our top loci indicate 
      potential interest and should be replicated in larger cohorts.
CI  - Copyright (c) 2022 Elsevier Masson SAS. All rights reserved.
FAU - Khamis, Amna
AU  - Khamis A
AD  - Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), 
      Institut Pasteur de Lille, F-59000, France; University of Lille, Lille University 
      Hospital, Lille, F-59000, France; Department of Metabolism, Digestion and 
      Reproduction, Imperial College London, London, United Kingdom. Electronic 
      address: amna.khamis@cnrs.fr.
FAU - Ning, Lijiao
AU  - Ning L
AD  - Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), 
      Institut Pasteur de Lille, F-59000, France; University of Lille, Lille University 
      Hospital, Lille, F-59000, France.
FAU - Balkau, Beverley
AU  - Balkau B
AD  - University Paris-Saclay, UVSQ, University. Paris-Sud, Inserm U1018, CESP, 
      Clinical Epidemiology, 94807 Villejuif, France.
FAU - Bonnefond, Amelie
AU  - Bonnefond A
AD  - Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), 
      Institut Pasteur de Lille, F-59000, France; University of Lille, Lille University 
      Hospital, Lille, F-59000, France; Department of Metabolism, Digestion and 
      Reproduction, Imperial College London, London, United Kingdom.
FAU - Canouil, Mickael
AU  - Canouil M
AD  - Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), 
      Institut Pasteur de Lille, F-59000, France; University of Lille, Lille University 
      Hospital, Lille, F-59000, France.
FAU - Roussel, Ronan
AU  - Roussel R
AD  - Department of Diabetology, Endocrinology and Nutrition, DHU-FIRE, HUPNVS, AP-HP, 
      Paris, France; Universite de Paris, UFR de Medecine, Paris, France; Centre de 
      Recherche des Cordeliers, Inserm U1138, Paris, France.
FAU - Froguel, Philippe
AU  - Froguel P
AD  - Inserm U1283, CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), 
      Institut Pasteur de Lille, F-59000, France; University of Lille, Lille University 
      Hospital, Lille, F-59000, France; Department of Metabolism, Digestion and 
      Reproduction, Imperial College London, London, United Kingdom. Electronic 
      address: p.froguel@imperial.ac.uk.
LA  - eng
PT  - Journal Article
DEP - 20220412
PL  - France
TA  - Diabetes Metab
JT  - Diabetes & metabolism
JID - 9607599
RN  - 0 (Glycated Hemoglobin A)
SB  - IM
MH  - CpG Islands
MH  - DNA Methylation/genetics
MH  - *Diabetes Mellitus, Type 2/epidemiology/genetics
MH  - Epigenesis, Genetic
MH  - Genome-Wide Association Study
MH  - Glycated Hemoglobin
MH  - Humans
MH  - *Hyperglycemia/genetics
OTO - NOTNLM
OT  - Epigenetics
OT  - Hyperglycaemia exposure
OT  - Longitudinal
OT  - Methylation
COIS- Declaration of interests The authors report no conflict of interest.
EDAT- 2022/04/16 06:00
MHDA- 2022/08/03 06:00
CRDT- 2022/04/15 20:11
PHST- 2022/03/08 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/04/16 06:00 [pubmed]
PHST- 2022/08/03 06:00 [medline]
PHST- 2022/04/15 20:11 [entrez]
AID - S1262-3636(22)00030-1 [pii]
AID - 10.1016/j.diabet.2022.101347 [doi]
PST - ppublish
SO  - Diabetes Metab. 2022 Jul;48(4):101347. doi: 10.1016/j.diabet.2022.101347. Epub 
      2022 Apr 12.