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Circulating metabol...
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Lamichhane, SantoshTurku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland
(author)
Circulating metabolic signatures of rapid and slow progression to type 1 diabetes in islet autoantibody-positive children
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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Frontiers Media S.A.2023
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LIBRIS-ID:oai:DiVA.org:oru-108526
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-108526URI
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https://doi.org/10.3389/fendo.2023.1211015DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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This study was supported by the Novo Nordisk Foundation (NNF18OC0034506, to MO), Juvenile Diabetes Research Foundation (2-SRA-2014-159-Q-R, to MO, TH, RL, and MKn), Academy of Finland (Centre of Excellence in Molecular Systems Immunology and Physiology Research – SyMMyS, Decision No. 250114, to RL, JT, MO, RL, and MKn; and Personalised Health 2014 programme project, Decision No. 292568, to RL, JT, MO, RL, and MKn). Further support was received by the Academy of Finland postdoctoral grant (No. 323171 to SL) and (grant no. 333981 to MO), “Inflammation in human early life: targeting impacts on life-course health” (INITIALISE) consortium funded by the Horizon Europe Program of the European Union under Grant Agreement 101094099 (to MO), the Medical Research Funds, Tampere and Helsinki University Hospitals (to MKn), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530) and Turku University Hospital (to MO, RL, and JT).
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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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Sen, ParthoTurku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland
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Dickens, Alex M.Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku, University, Turku, Finland
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Kråkström, MatildaTurku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland
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Ilonen, JormaImmunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
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Lempainen, JohannaImmunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland; Department of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland; Clinical Microbiology, Turku University Hospital, Turku, Finland
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Hyöty, HeikkiFaculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland
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Lahesmaa, RiittaTurku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland; InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Institute of Biomedicine, University of Turku, Turku, Finland
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Veijola, RiittaDepartment of Pediatrics, PEDEGO Research Unit, Medical Research Centre, University of Oulu, Oulu, Finland; Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland
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Toppari, JormaDepartment of Pediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland; Institute of Biomedicine, Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland
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Hyötyläinen, Tuulia,1971-Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)tihn
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Knip, MikaelResearch Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland
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Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland(Swepub:oru)moc
(author)
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Turku Bioscience, University of Turku and Åbo Akademi University, Turku, FinlandTurku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland; Department of Chemistry, University of Turku, University, Turku, Finland
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