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Pflueger, M. ; Seppänen-Laakso, T.* ; Suortti, T.* ; Hyötyläinen, T.* ; Achenbach, P. ; Bonifacio, E.* ; Oresič, M.* ; Ziegler, A.-G.

Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes.

Diabetes 60, 2740-2747 (2011)

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Open Access Green as soon as Postprint is submitted to ZB.

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Antibody standardization program; Autoantibodies; Appearance; Childhood; Pathogenesis; Methionine; Parents; Assays; Diet

ISSN (print) / ISBN 0012-1797

e-ISSN 1939-327X

Journal Diabetes

Quellenangaben Volume: 60, Issue: 11, Pages: 2740-2747

Publisher American Diabetes Association

Publishing Place Alexandria, VA.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)