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  • Oresic, Matej,1967-VTT Technical Research Centre of Finland, Espoo, Finland (author)

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes

  • Article/chapterEnglish2008

Publisher, publication year, extent ...

  • 2008-12-15
  • New York, USA :Rockefeller University Press,2008
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-59350
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-59350URI
  • https://doi.org/10.1084/jem.20081800DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies:Juvenile Diabetes Research Foundation International, Projektnr. 4-1999-731, 4-2001-435 European Community, Projektnr. HEALTH-F2-2008-202013Academy of FinlandSigrid Juselius FoundationPaivikki and Sakari Sohlberg FoundationSigne and Ane Gyllenberg FoundationDiabetes Research Foundation, FinlandSpecial Federal Funds to the Turku, OuluTampere University Hospitals
  • The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Simell, SatuDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • Sysi-Aho, MarkoVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Näntö-Salonen, KirstiDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • Seppänen-Laakso, TuulikkiVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Parikka, VilhelmiinaDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • Katajamaa, MikkoVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Hekkala, AnneDepartment of Pediatrics, University of Oulu, Oulu, Finland (author)
  • Mattila, IsmoVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Keskinen, PäiviDepartment of Pediatrics, Tampere University Hospital, Tampere, Finland (author)
  • Yetukuri, LaxmanVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Reinikainen, ArjaTurku Centre for Biotechnology, Turku, Finland (author)
  • Lähde, JyrkiDepartment of Pediatrics, Tampere University Hospital, Tampere, Finland (author)
  • Suortti, TapaniVTT Technical Research Centre of Finland, Espoo, Finland (author)
  • Hakalax, JariDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • Simell, TuulaDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • Hyöty, HeikkiDepartment of Virology, University of Tampere, Tampere, Finland; Centre for Laboratory Medicine, University Hospital of Tampere, Tampere, Finland (author)
  • Veijola, RiittaDepartment of Pediatrics, University of Oulu, Oulu, Finland (author)
  • Ilonen, JormaDepartment of Clinical Microbiology, University of Kuopio, Kuopio, Finland (author)
  • Lahesmaa, RiittaTurku Centre for Biotechnology, Turku, Finland (author)
  • Knip, MikaelDepartment of Pediatrics, Tampere University Hospital, Tampere, Finland; Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland (author)
  • Simell, OlliDepartment of Pediatrics, University of Turku, Turku, Finland (author)
  • VTT Technical Research Centre of Finland, Espoo, FinlandDepartment of Pediatrics, University of Turku, Turku, Finland (creator_code:org_t)

Related titles

  • In:Journal of Experimental MedicineNew York, USA : Rockefeller University Press205:13, s. 2975-29840022-10071540-9538

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