title: Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study.
abstract: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes.
  
  
  
  Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites.
  
  
  
  Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age.
  
  
  
  Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.
authors.affiliation: Department of Pediatric Research, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.|Hormone Laboratory, Department of Medical Biochemistry, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Jørgenrud
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: German
authors.initials: G
authors.lastname: Tapia
authors.affiliation: Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Håkon
authors.initials: H
authors.lastname: Bøås
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Milaim
authors.initials: M
authors.lastname: Pepaj
authors.affiliation: Division of Diagnostic and Intervention, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Berg
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Thorsby
authors.affiliation: Systems Medicine Department, Steno Diabetes Centre, Gentofte, Denmark.|VTT Technical Research Centre of Finland, Espoo, Finland.
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.affiliation: Systems Medicine Department, Steno Diabetes Centre, Gentofte, Denmark.|VTT Technical Research Centre of Finland, Espoo, Finland.
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyötyläinen
authors.affiliation: Department of Pediatric Research, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
mesh_terms: D015551:Autoimmunity; D001774:Blood Chemical Analysis; D001942:Breast Feeding; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D055442:Metabolome; D009664:Norway; D012307:Risk Factors
keywords: autoimmunity; breast feeding; diabetes mellitus, type 1; metabolome; metabolomics