Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetesInFLAMES Research Flagship Center, University of Turku, Turku, Finland; Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland.
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
Immunogenetics Laboratory, University of Turku, Turku, Finland.
InFLAMES Research Flagship Center, University of Turku, Turku, Finland; Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland; Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland.
Department of Pediatrics, Research Unit of Clinical Medicine, Medical Research Center, University of Oulu, Oulu, Finland; Department for Children and Adolescents, Medical Research Center, Oulu University Hospital, Oulu, Finland.
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Fimlab Laboratories, Tampere, Finland.
Department of Computer Science, Aalto University School of Science, Aalto, Finland.
Pediatric Research Center, New Children's Hospital, Helsinki University Hospital, Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Department of Computer Science, Aalto University School of Science, Aalto, Finland.
Turku Bioscience Centre, 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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2023 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 15941
Article in journal (Refereed) Published
Abstract [en]
Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.
Place, publisher, year, edition, pages
Nature Publishing Group, 2023. Vol. 13, no 1, article id 15941
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-108493DOI: 10.1038/s41598-023-43039-4ISI: 001104198800008PubMedID: 37743383Scopus ID: 2-s2.0-85171842365OAI: oai:DiVA.org:oru-108493DiVA, id: diva2:1799828
Funder
Academy of Finland, 337530; 287423; 335858; 292335; 294337; 31444; 319280; 329277; 331790; 308067; 288671Novo Nordisk Foundation
Note
This study was supported by the InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530) and JDRF Grant 1-SRA-2017-357-Q-R to M.O., M.K. and R.L. M.K.H. was supported by Turku Doctoral Programme of Molecular Medicine (TuDMM) and grants by Turku University Foundation, Finnish Cultural Foundation (Grant 85182227), Kyllikki and Uolevi Lehikoinen Foundation and Finnish Diabetes Research Foundation. N.L. received funding from the Academy of Finland (Grant 287423). L.C. received funding from the Academy of Finland (Grant 335858). R.L. received funding from the Academy of Finland (Grants 292335, 294337, 31444, 319280, 329277, 331790), Business Finland and grants from the Sigrid Juselius Foundation (SJF), Jane and Aatos Erkko Foundation, Novo Nordisk Foundation, Finnish Diabetes Foundation and the Finnish Cancer Foundation. R.L., H.L., M.K., M.O. and J.T. were supported by the Academy of Finland, Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) Grant 250114 and Grant 292482. J.T. was funded by EFSD, Pediatric Research Foundation, and Turku University Hospital Special Governmental Grants. R.V. received funding for the DIPP study from the JDRF (Grants 1-SRA-2016-342-M-R and 1-SRA-2019-732-M-B), the Academy of Finland (Grant 308067) and the Finnish Diabetes Foundation. H.H. received a grant from the Academy of Finland (Grant 288671) and Novo Nordisk Foundation. The DIPP Study was also supported by Special Research Funds for University Hospitals in Finland. Our research is as well supported by University of Turku Graduate School (UTUGS) and Biocenter Finland.
2023-09-252023-09-252024-04-08Bibliographically approved