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Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children

  • Lamichhane, Santosh1
  • Sen, Partho1
  • Dickens, Alex M.1, 2
  • Kråkström, Matilda1
  • Ilonen, Jorma3
  • Lempainen, Johanna3, 4, 5
  • Hyöty, Heikki6, 7
  • Lahesmaa, Riitta1, 8, 9
  • Veijola, Riitta10, 11
  • Toppari, Jorma4, 12
  • Hyötyläinen, Tuulia13
  • Knip, Mikael14, 15
  • Orešič, Matej1, 16
  • 1 Turku Bioscience, University of Turku and Åbo Akademi University, Turku , (Finland)
  • 2 Department of Chemistry, University of Turku, University, Turku , (Finland)
  • 3 Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku , (Finland)
  • 4 Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku , (Finland)
  • 5 Clinical Microbiology, Turku University Hospital, Turku , (Finland)
  • 6 Faculty of Medicine and Life Sciences, University of Tampere, Tampere , (Finland)
  • 7 Fimlab Laboratories, Pirkanmaa Hospital District, Tampere , (Finland)
  • 8 InFLAMES Research Flagship Center, University of Turku, Turku , (Finland)
  • 9 Institute of Biomedicine, University of Turku, Turku , (Finland)
  • 10 Department of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu , (Finland)
  • 11 Department of Children and Adolescents, Oulu University Hospital, Oulu , (Finland)
  • 12 Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku , (Finland)
  • 13 School of Science and Technology, Örebro University, Örebro , (Sweden)
  • 14 Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki , (Finland)
  • 15 Department of Pediatrics, Tampere University Hospital, Tampere , (Finland)
  • 16 School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro , (Sweden)
Published Article
Frontiers in Endocrinology
Frontiers Media SA
Publication Date
Sep 06, 2023
DOI: 10.3389/fendo.2023.1211015
  • Endocrinology
  • Original Research


Aims/hypothesis Appearance of multiple islet cell autoantibodies in early life is indicative of future progression to overt type 1 diabetes, however, at varying rates. Here, we aimed to study whether distinct metabolic patterns could be identified in rapid progressors (RP, disease manifestation within 18 months after the initial seroconversion to autoantibody positivity) vs. slow progressors (SP, disease manifestation at 60 months or later from the appearance of the first autoantibody). Methods Longitudinal samples were collected from RP (n=25) and SP (n=41) groups at the ages of 3, 6, 12, 18, 24, or ≥ 36 months. We performed a comprehensive metabolomics study, analyzing both polar metabolites and lipids. The sample series included a total of 239 samples for lipidomics and 213 for polar metabolites. Results We observed that metabolites mediated by gut microbiome, such as those involved in tryptophan metabolism, were the main discriminators between RP and SP. The study identified specific circulating molecules and pathways, including amino acid (threonine), sugar derivatives (hexose), and quinic acid that may define rapid vs. slow progression to type 1 diabetes. However, the circulating lipidome did not appear to play a major role in differentiating between RP and SP. Conclusion/interpretation Our study suggests that a distinct metabolic profile is linked with the type 1 diabetes progression. The identification of specific metabolites and pathways that differentiate RP from SP may have implications for early intervention strategies to delay the development of type 1 diabetes.

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