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

Oresic, Matej, 1967- (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Simell, Satu (författare)
Department of Pediatrics, University of Turku, Turku, Finland
Sysi-Aho, Marko (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
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Näntö-Salonen, Kirsti (författare)
Department of Pediatrics, University of Turku, Turku, Finland
Seppänen-Laakso, Tuulikki (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Parikka, Vilhelmiina (författare)
Department of Pediatrics, University of Turku, Turku, Finland
Katajamaa, Mikko (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Hekkala, Anne (författare)
Department of Pediatrics, University of Oulu, Oulu, Finland
Mattila, Ismo (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Keskinen, Päivi (författare)
Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Yetukuri, Laxman (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Reinikainen, Arja (författare)
Turku Centre for Biotechnology, Turku, Finland
Lähde, Jyrki (författare)
Department of Pediatrics, Tampere University Hospital, Tampere, Finland
Suortti, Tapani (författare)
VTT Technical Research Centre of Finland, Espoo, Finland
Hakalax, Jari (författare)
Department of Pediatrics, University of Turku, Turku, Finland
Simell, Tuula (författare)
Department of Pediatrics, University of Turku, Turku, Finland
Hyöty, Heikki (författare)
Department of Virology, University of Tampere, Tampere, Finland; Centre for Laboratory Medicine, University Hospital of Tampere, Tampere, Finland
Veijola, Riitta (författare)
Department of Pediatrics, University of Oulu, Oulu, Finland
Ilonen, Jorma (författare)
Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland
Lahesmaa, Riitta (författare)
Turku Centre for Biotechnology, Turku, Finland
Knip, Mikael (författare)
Department of Pediatrics, Tampere University Hospital, Tampere, Finland; Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland
Simell, Olli (författare)
Department of Pediatrics, University of Turku, Turku, Finland
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 (creator_code:org_t)
2008-12-15
2008
Engelska.
Ingår i: Journal of Experimental Medicine. - New York, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 205:13, s. 2975-2984
Relaterad länk:
http://jem.rupress.o...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Immunologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Immunology (hsv//eng)

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