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Steck, A.K.* ; Vehik, K.* ; Bonifacio, E.* ; Lernmark, A.* ; Ziegler, A.-G. ; Hagopian, W.A.* ; She, J.* ; Simell, O.* ; Akolkar, B.* ; Krischer, J.* ; Schatz, D.* ; Rewers, M.J.* ; TEDDY Study Group (Beyerlein, A. ; Hummel, M. ; Hummel, S. ; Knopff, A. ; Peplow, C. ; Roth, R. ; Stock, J. ; Strauss, E. ; Warncke, K. ; Winkler, C.)

Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY).

Diabetes Care 38, 808-813 (2015)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
OBJECTIVE: While it is known that there is progression to diabetes in <10 years in 70% of children with two or more islet autoantibodies, predictors of the progression to diabetes are only partially defined. RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study has observed 8,503 children who were at increased genetic risk for autoimmune diabetes. Insulin autoantibodies (IAAs), GAD65 autoantibodies (GADAs), and insulinoma-associated protein 2 autoantibodies (IA-2As) were measured every 3 months until 4 years of age and every 6 months thereafter; if results were positive, the autoantibodies were measured every 3 months. RESULTS: Life table analysis revealed that the cumulative incidence of diabetes by 5 years since the appearance of the first autoantibody differed significantly by the number of positive autoantibodies (47%, 36%, and 11%, respectively, in those with three autoantibodies, two autoantibodies, and one autoantibody, P < 0.001). In time-varying survival models adjusted for first-degree relative status, number of autoantibodies, age at first persistent confirmed autoantibodies, and HLA genotypes, higher mean IAA and IA-2A levels were associated with an increased risk of type 1 diabetes in children who were persistently autoantibody positive (IAAs: hazard ratio [HR] 8.1 [95% CI 4.6-14.2]; IA-2A: HR 7.4 [95% CI 4.3-12.6]; P < 0.0001]. The mean GADA level did not significantly affect the risk of diabetes. CONCLUSIONS: In the TEDDY study, children who have progressed to diabetes usually expressed two or more autoantibodies. Higher IAA and IA-2A levels, but not GADA levels, increased the risk of diabetes in those children who were persistently autoantibody positive.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glutamic-acid Decarboxylase; General-population; Prevention Trial-type-1; Risk Score; Type-1; Children; Insulin; Autoimmunity; Individuals; Association
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 38, Issue: 5, Pages: 808-813 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research Type 1 (IDF)