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Cited by 449Diabetes and associated disordersMetabolomics and Mass Spectrometry StudiesDiabetes Management and Research

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

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Orešič, Matej, Simell, Satu, Sysi-Aho, Marko, Näntö-Salonen, Kirsti, Seppänen-Laakso, Tuulikki, Parikka, Vilhelmiina, Katajamaa, Mikko, Hekkala, Anne +14 more·2008·The Journal of Experimental Medicine
DOI 10.1084/jem.20081800PMC PMC2605239
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Abstract

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward β 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.

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  • Lipid and metabolite profiles can serve as markers for impending type 1 diabetes; these markers include decreased phosphatidylcholine at birth, and reduced triglycerides and antioxidant ether phospholipids followed by increased proinflammatory lysophosphatidylcholine several months before seroconversion to autoantibody positivity.

    “Lipid and metabolite profiles can also serve as markers for impending type 1 diabetes; these markers include decreased phosphatidylcholine at birth, and reduced triglycerides and antioxidant ether phospholipids followed by increased proinflammatory lysophosphatidylcholine several months before seroconversion to auto antibody positivity.70”

    From Type 1 diabetes (2014) · cites this paper as [70]

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Authors
Orešič, M., Simell, S., Sysi-Aho, M., Näntö-Salonen, K., Seppänen-Laakso, T., Parikka, V., Katajamaa, M., Hekkala, A., Mattila, I., Keskinen, P., Yetukuri, L., Reinikainen, A., Lähde, J., Suortti, T., Hakalax, J., Simell, T., Hyöty, H., Veijola, R., Ilonen, J., Lahesmaa, R., Knip, M., & Simell, O.
Affiliations
  • 1VTT Technical Research Centre of Finland, Espoo FI-02044, Finland
  • 2Department of Pediatrics
  • VTT Technical Research Centre of Finland (FI)
  • University of Oulu (FI)
  • 5Department of Pediatrics, Tampere University Hospital, Tampere FI-33521, Finland
  • Turku Centre for Biotechnology (FI)
  • 7Department of Virology, University of Tampere, Tampere FI-33520, Finland
  • University of Turku (FI)
  • University of Helsinki (FI)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2008-12-15
Volume
205
Issue
13
Pages
2975-2984
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20081800
PMC
PMC2605239
OpenAlex
W2112530229
Cited by
449
References
3
Citations by year
2026: 11 · 2025: 13 · 2024: 20 · 2023: 16 · 2022: 25 · 2021: 30 · 2020: 25 · 2019: 25 · 2018: 18 · 2017: 29 · 2016: 29 · 2015: 27 · 2014: 21 · 2013: 35 · 2012: 43
FWCI
15.62
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 1 diabetes, islet autoimmunity, serum metabolome, lipid metabolism, amino acid metabolism, succinic acid, phosphatidylcholine, lysophosphatidylcholine, triglycerides, glutamate, glutamic acid decarboxylase antibodies, insulin autoantibodies, beta-cell failure, children, type 1 diabetes prevention
MeSH terms
Adolescent, Amino Acids, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Finland, Humans, Infant, Islets of Langerhans, Male, Metabolic Diseases, Autoimmunity, Disease Progression, Lipid Metabolism, Metabolomics

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