Daniela Much1,2,3,4, Andreas Beyerlein1,4, Alida Kindt4,5, Jan Krumsiek4,5, Ferdinand Stückler4,5, Michaela Rossbauer1,2,3, Anna Hofelich1,4, David Wiesenäcker1,2,6, Susanne Hivner1,2,3,4, Melanie Herbst1,2,3,4, Werner Römisch-Margl4,7, Cornelia Prehn8, Jerzy Adamski4,8,9, Gabi Kastenmüller4,7, Fabian Theis4,5, Anette-G Ziegler1,2,3,4, Sandra Hummel10,11,12,13. 1. Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany. 2. Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 3. Forschergruppe Diabetes e.V., Neuherberg, Germany. 4. German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. 5. Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany. 6. Department of Pediatrics, Kinderklinik München Schwabing, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. 7. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, Germany. 8. Genome Analysis Center, Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany. 9. Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany. 10. Institute of Diabetes Research, Helmholtz Zentrum München, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de. 11. Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. sandra.hummel@helmholtz-muenchen.de. 12. Forschergruppe Diabetes e.V., Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de. 13. German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany. sandra.hummel@helmholtz-muenchen.de.
Abstract
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/ INTERPRETATION: 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.
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