title: The role of global and regional DNA methylation and histone modifications in glycemic traits and type 2 diabetes: A systematic review.
abstract: New evidence suggests the potential involvement of epigenetic mechanisms in type 2 diabetes (T2D) as a crucial interface between the effects of genetic predisposition and environmental influences.
  
  
  
  To systematically review studies investigating the association between epigenetic marks (DNA methylation and histone modifications) with T2D and glycemic traits (glucose and insulin levels, insulin resistance measured by HOMA-IR).
  
  
  
  Six bibliographic databases (Embase.com, Medline (Ovid), Web-of-Science, PubMed, Cochrane Central and Google Scholar) were screened until 28th August 2015. We included randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined the association between epigenetic marks (global, candidate or genome-wide methylation of DNA and histone modifications) with T2D, glucose and insulin levels and insulin metabolism. Of the initially identified 3879 references, 53 articles, based on 47 unique studies met our inclusion criteria. Overall, data were available on 10,823 participants, with a total of 3358 T2D cases. There was no consistent evidence for an association between global DNA-methylation with T2D, glucose, insulin and insulin resistance. The studies reported epigenetic regulation of several candidate genes for diabetes susceptibility in blood cells, muscle, adipose tissue and placenta to be related with T2D without any general overlap between them. Histone modifications in relation to T2D were reported only in 3 observational studies.
  
  
  
  Current evidence supports an association between epigenetic marks and T2D. However, overall evidence is limited, highlighting the need for further larger-scale and prospective investigations to establish whether epigenetic marks may influence the risk of developing T2D.
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: t.muka@erasmusmc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Muka
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Nano
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Voortman
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: K V E
authors.initials: KVE
authors.lastname: Braun
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Ligthart
authors.affiliation: Department of Population Health, Luxembourg Institute of Health, Luxembourg.
authors.forename: S
authors.initials: S
authors.lastname: Stranges
authors.affiliation: Medical Library, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: W M
authors.initials: WM
authors.lastname: Bramer
authors.affiliation: Research and Development, Metagenics, Inc, USA.
authors.forename: J
authors.initials: J
authors.lastname: Troup
authors.affiliation: Department of Public Health & Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Chowdhury
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Dehghan
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: O H
authors.initials: OH
authors.lastname: Franco
mesh_terms: D000107:Acetylation; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D010641:Phenotype; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006657:Histones; D007328:Insulin
keywords: Epigenetics; Global DNA methylation; Glucose; Histone modification; Insulin; Insulin resistance; Type 2 diabetes