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Hoffmann, V. ; Weiß, A. ; Winkler, C. ; Knopff, A. ; Jolink, M. ; Bonifacio, E. ; Ziegler, A.-G.

Landmark models to define the age-adjusted risk of developing stage 1 type 1 diabetes across childhood and adolescence.

BMC Med. 17:125 (2019)

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BackgroundAutoimmune diseases are often preceded by an asymptomatic autoantibody-positive phase. In type 1 diabetes, the detection of autoantibodies to pancreatic islet antigens in genetically at-risk children is prognostic for future clinical diabetes. Testing for islet autoantibodies is, therefore, performed in a range of clinical studies. Accurate risk estimates that consider the a priori genetic risk and other risk modifiers are an important component of screening. The age of an individual is an under-appreciated risk modifier. The aim of this study was to provide age-adjusted risk estimates for the development of autoantibodies across childhood in genetically at-risk children.MethodsThe prospective BABYDIAB and BABYDIET studies included 2441 children from birth who had a first-degree relative with type 1 diabetes. Children were born between 1989 and 2006 and were regularly followed from birth for the development of islet autoantibodies and diabetes. A landmark analysis was performed to estimate the risk of islet autoantibodies at birth and at the age 3.5, 6.5 and 12.5years. Exponential decay curves were fitted for the risk by the age of 20years.ResultsThe risk of islet autoantibodies by the age of 20years was 8%, 4.6%, 2.6% and 0.9%, at the landmark ages of birth, 3.5, 6.5 and 12.5years, respectively. The short-term risks (within 6years of follow-up) at these landmark ages were 5.3%, 2.9%, 1.8% and 1%, respectively. The decline in autoantibody risk with age was modelled using a one-phase exponential decay curve (r=0.99) with a risk half-life of 3.7years. This risk decay model was remarkably consistent when the outcome was defined as islet autoantibody-positive or multiple islet autoantibody-positive and when the study cohort was stratified by HLA risk genotype. A similar decay model was observed for coeliac disease-associated transglutaminase antibodies in the same cohort. Unlike the risk of developing islet autoantibodies, the rate of developing clinical diabetes in children who were islet autoantibody-positive did not decline with age.ConclusionThe risk of developing autoantibodies drops exponentially with age in children with a first-degree relative with type 1 diabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Autoimmunity ; Islet Autoantibodies ; Type 1 Diabetes ; Landmark Risk; Islet Autoantibodies; Children; Autoimmunity; Intervention; Progression; Appearance; Diagnosis; Parents; Markers

ISSN (print) / ISBN 1741-7015

e-ISSN 1741-7015

Journal BMC Medicine

Quellenangaben Volume: 17, Issue: 1, Article Number: 125

Publisher BioMed Central

Publishing Place Campus, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes Research Type 1 (IDF)
Institute for Pancreatic Beta Cell Research (IPI)