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Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes
Forschergruppe Diabetes e.V., Helmholtz Center Munich, Neuherberg, Germany.
VTT Technical Research Centre of Finland, Espoo, Finland.
Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland.
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2011 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 11, p. 2740-2747Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Islet autoimmunity precedes type 1 diabetes and often initiates in childhood. Phenotypic variation in islet autoimmunity relative to the age of its development suggests heterogeneous mechanisms of autoimmune activation. To support this notion, we examined whether serum metabolite profiles differ between children with respect to islet autoantibody status and the age of islet autoantibody development.

RESEARCH DESIGN AND METHODS: The study analyzed 29 metabolites of amino acid metabolism and 511 lipids assigned to 12 lipid clusters in children, with a type 1 diabetic parent, who first developed autoantibodies at age 2 years or younger (n = 13), at age 8 years or older (n = 22), or remained autoantibody-negative, and were matched for age, date of birth, and HLA genotypes (n = 35). Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.

RESULTS: Differences in the metabolite profiles were observed relative to age and islet autoantibody status. Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001). Consistent with our hypothesis, children who developed autoantibodies by age 2 years had twofold lower concentration of methionine compared with those who developed autoantibodies in late childhood or remained autoantibody-negative (P < 0.0001).

CONCLUSIONS: Distinct metabolic profiles are associated with age and islet autoimmunity. Pathways that use methionine are potentially relevant for developing islet autoantibodies in early infancy.

Place, publisher, year, edition, pages
2011. Vol. 60, no 11, p. 2740-2747
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-63653DOI: 10.2337/db10-1652ISI: 000296954600012PubMedID: 22025777Scopus ID: 2-s2.0-80755152896OAI: oai:DiVA.org:oru-63653DiVA, id: diva2:1169217
Note

German Federal Ministry of Education and Research (BMBF) BABYDIAB 01KD89030 1KD9601 FKZ 01GI0805-07 

Juvenile Diabetes Research Foundation BABYDIAB JDRF 1-2006-665 11-2005-1117 

European Union EP7-HEALTH-2007 DIAPREPP N202013 

DFG-CRTD  

Dresden University FZ 111 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-30Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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