title: Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk.
abstract: Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight (BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch-up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy-five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM [the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study] or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long-term risk for diseases such as type 2 diabetes.
authors.affiliation: Mammalian Molecular Genetics Group, Department of Pathology, crq20@cam.ac.uk.
authors.forename: Claire R
authors.initials: CR
authors.lastname: Quilter
authors.affiliation: Metabolic Research Laboratories, Medical Research Council (MRC) Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, National Institute for Health Research Cambridge Biomedical Research Centre, Centre for Trophoblast Research, and.
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Cooper
authors.affiliation: Mammalian Molecular Genetics Group, Department of Pathology.
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Cliffe
authors.affiliation: Mammalian Molecular Genetics Group, Department of Pathology.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Skinner
authors.affiliation: National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Department of Paediatrics, University of Cambridge, Cambridge, UK; and.
authors.forename: Philippa M
authors.initials: PM
authors.lastname: Prentice
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine Chicago, Chicago, Illinois, USA.
authors.forename: LaTasha
authors.initials: L
authors.lastname: Nelson
authors.affiliation: Mammalian Molecular Genetics Group, Department of Pathology.
authors.forename: Julien
authors.initials: J
authors.lastname: Bauer
authors.affiliation: National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Department of Paediatrics, University of Cambridge, Cambridge, UK; and.
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.affiliation: Metabolic Research Laboratories, Medical Research Council (MRC) Metabolic Diseases Unit, Department of Obstetrics and Gynaecology, National Institute for Health Research Cambridge Biomedical Research Centre, Centre for Trophoblast Research, and.
authors.forename: Miguel
authors.initials: M
authors.lastname: Constância
authors.affiliation: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine Chicago, Chicago, Illinois, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Lowe
authors.affiliation: Mammalian Molecular Genetics Group, Department of Pathology.
authors.forename: Nabeel A
authors.initials: NA
authors.lastname: Affara
authors.affiliation: National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Trust-MRC Institute of Metabolic Science, Department of Paediatrics, University of Cambridge, Cambridge, UK; and.
authors.forename: David B
authors.initials: DB
authors.lastname: Dunger
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D016640:Diabetes, Gestational / Q000209:etiology*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D008297:Male; D011247:Pregnancy; D012306:Risk; D015430:Weight Gain / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose
keywords: epigenetics; fetal programming; maternal environment