PuSH - Publication Server of Helmholtz Zentrum München

Bonifacio, E. ; Weiß, A. ; Winkler, C. ; Hippich, M. ; Rewers, M.J.* ; Toppari, J.* ; Lernmark, A.* ; She, J.X.* ; Hagopian, W.A.* ; Krischer, J.P.* ; Vehik, K.* ; Schatz, D.A.* ; Akolkar, B.* ; Ziegler, A.-G.

An age-related exponential decline in the risk of multiple islet autoantibody seroconversion during childhood.

Diabetes Care 44, 2260-2268 (2021)
Publ. Version/Full Text DOI PMC
Free by publisher
Open Access Green as soon as Postprint is submitted to ZB.
OBJECTIVE: Islet autoimmunity develops before clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for presymptomatic type 1 diabetes. RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young study prospectively monitored 8,556 genetically at-risk children at 3- to 6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models. RESULTS: The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% CI 3.8-4.7) at 7.5 months of age and declined to 1.1% (95% CI 0.8-1.3) at a landmark age of 6.25 years (P < 0.0001). Risk decline was slight or absent in single insulin and GAD autoantibody phenotypes. The influence of sex, HLA, and other susceptibility genes on risk subsided with increasing age and was abrogated by age 6 years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5-7 years of age. CONCLUSIONS: The risk of developing islet autoimmunity declines exponentially with age, and the influence of major genetic factors on this risk is limited to the first few years of life.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glutamic-acid Decarboxylase; Type-1; Children; Assays; Time
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 44, Issue: 10, Pages: 2260-2268 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)
Institute for Pancreatic Beta Cell Research (IPI)