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Weiss, A. ; Zapardiel-Gonzalo, J. ; Voss, F. ; Jolink, M. ; Stock, J. ; Haupt, F. ; Kick, K.* ; Welzhofer, T.C.* ; Heublein, A. ; Winkler, C. ; Achenbach, P. ; Ziegler, A.-G. ; Bonifacio, E.

Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening.

Diabetologia 65, 93-104 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
AIMS/HYPOTHESIS: The aim of this study was to develop strategies that identify children from the general population who have late-stage presymptomatic type 1 diabetes and may, therefore, benefit from immune intervention. METHODS: We tested children from Bavaria, Germany, aged 1.75-10 years, enrolled in the Fr1da public health screening programme for islet autoantibodies (n=154,462). OGTT and HbA1c were assessed in children with multiple islet autoantibodies for diagnosis of presymptomatic stage 1 (normoglycaemia) or stage 2 (dysglycaemia) type 1 diabetes. Cox proportional hazards and penalised logistic regression of autoantibody, genetic, metabolic and demographic information were used to develop a progression likelihood score to identify children with stage 1 type 1 diabetes who progressed to stage 3 (clinical) type 1 diabetes within 2 years. RESULTS: Of 447 children with multiple islet autoantibodies, 364 (81.4%) were staged. Undiagnosed stage 3 type 1 diabetes, presymptomatic stage 2, and stage 1 type 1 diabetes were detected in 41 (0.027% of screened children), 30 (0.019%) and 293 (0.19%) children, respectively. The 2 year risk for progression to stage 3 type 1 diabetes was 48% (95% CI 34, 58) in children with stage 2 type 1 diabetes (annualised risk, 28%). HbA1c, islet antigen-2 autoantibody positivity and titre, and the 90 min OGTT value were predictors of progression in children with stage 1 type 1 diabetes. The derived progression likelihood score identified substages corresponding to ≤90th centile (stage 1a, n=258) and >90th centile (stage 1b, n=29; 0.019%) of stage 1 children with a 4.1% (95% CI 1.4, 6.7) and 46% (95% CI 21, 63) 2 year risk of progressing to stage 3 type 1 diabetes, respectively. CONCLUSIONS/INTERPRETATION: Public health screening for islet autoantibodies found 0.027% of children to have undiagnosed clinical type 1 diabetes and 0.038% to have undiagnosed presymptomatic type 1 diabetes. Of the latter group, our novel likelihood ratio score predicted approximately 50% risk of developing clinical diabetes within 2 years.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Clinical Trial Modelling ; Glucose Tolerance ; Immunotherapy ; Islet Autoantibodies ; Population Screening ; Progression Score ; Public Health Screening ; Type 1 Diabetes
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Zeitschrift Diabetologia
Quellenangaben Band: 65, Heft: 12, Seiten: 93-104 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort Berlin ; Heidelberg [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Pancreatic Beta Cell Research (IPI)
Institute of Diabetes Research Type 1 (IDF)
Förderungen Leona M. and Harry B. Helmsley Charitable Trust
Federal Ministry of Education and Research
LifeScience Stiftung