title: Lactation is associated with altered metabolomic signatures in women with gestational diabetes.
abstract: Lactation for >3 months in women with gestational diabetes is associated with a reduced risk of type 2 diabetes that persists for up to 15 years postpartum. However, the underlying mechanisms are unknown. We examined whether in women with gestational diabetes lactation for >3 months is associated with altered metabolomic signatures postpartum.
  
  
  
  We enrolled 197 women with gestational diabetes at a median of 3.6 years (interquartile range 0.7-6.5 years) after delivery. Targeted metabolomics profiles (including 156 metabolites) were obtained during a glucose challenge test. Comparisons of metabolite concentrations and ratios between women who lactated for >3 months and women who lactated for ≤3 months or not at all were performed using linear regression with adjustment for age and BMI at the postpartum visit, time since delivery, and maternal education level, and correction for multiple testing. Gaussian graphical modelling was used to generate metabolite networks.
  
  
  
  Lactation for >3 months was associated with a higher total lysophosphatidylcholine/total phosphatidylcholine ratio; in women with short-term follow-up, it was also associated with lower leucine concentrations and a lower total branched-chain amino acid concentration. Gaussian graphical modelling identified subgroups of closely linked metabolites within phosphatidylcholines and branched-chain amino acids that were affected by lactation for >3 months and have been linked to the pathophysiology of type 2 diabetes in previous studies.
  
  
  
  Lactation for >3 months in women with gestational diabetes is associated with changes in the metabolomics profile that have been linked to the early pathogenesis of type 2 diabetes.
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Much
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyerlein
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Alida
authors.initials: A
authors.lastname: Kindt
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Stückler
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Rossbauer
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hofelich
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Department of Pediatrics, Kinderklinik München Schwabing, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wiesenäcker
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Hivner
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Herbst
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.affiliation: Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.|Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.affiliation: German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.|Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.|Forschergruppe Diabetes e.V., Neuherberg, Germany.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany.
authors.forename: Anette-G
authors.initials: AG
authors.lastname: Ziegler
authors.affiliation: Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de.|Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. sandra.hummel@helmholtz-muenchen.de.|Forschergruppe Diabetes e.V., Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de.|German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hummel
mesh_terms: D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D006801:Humans; D007774:Lactation / Q000097:blood* / Q000502:physiology*; D007930:Leucine / Q000097:blood; D055432:Metabolomics / Q000379:methods; D049590:Postpartum Period / Q000097:blood* / Q000502:physiology*; D011247:Pregnancy
chemical_list: D000597:Amino Acids, Branched-Chain; D007930:Leucine
keywords: Gestational diabetes; Lactation; Metabolic networks; Metabolomic profile; Type 2 diabetes