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

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  1. Polyols and Branched Chained Amino Acids Are Associated with Present and Future Renal Impairment in Type 1 Diabetes

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  • Matej Oresic
  • Satu Simell
  • Marko Sysi-Aho
  • Kirsti Näntö-Salonen
  • Tuulikki Seppänen-Laakso
  • Vilhelmiina Parikka
  • Mikko Katajamaa
  • Anne Hekkala
  • Ismo Mattila
  • Päivi Keskinen
  • Laxman Yetukuri
  • Arja Reinikainen
  • Jyrki Lähde
  • Tapani Suortti
  • Jari Hakalax
  • Tuula Simell
  • Heikki Hyöty
  • Riitta Veijola
  • Jorma Ilonen
  • Riitta Lahesmaa
  • Mikael Knip
  • Olli Simell
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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.

Original languageEnglish
JournalJournal of Experimental Medicine
Volume205
Issue number13
Pages (from-to)2975-84
Number of pages10
ISSN0022-1007
DOIs
Publication statusPublished - 22 Dec 2008
Externally publishedYes

    Research areas

  • Adolescent, Amino Acids/metabolism, Autoantibodies/blood, Autoimmunity/immunology, Child, Child, Preschool, Diabetes Mellitus, Type 1/epidemiology, Disease Progression, Female, Finland/epidemiology, Humans, Infant, Islets of Langerhans/immunology, Lipid Metabolism, Male, Metabolic Diseases/immunology, Metabolomics

ID: 54987747