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Weiss, A. ; Chakievska, L. ; Achenbach, P. ; Hergl, M. ; Hummel, S. ; Ott, R. ; Scholz, M. ; Winkler, C. ; Bonifacio, E. ; Ziegler, A.-G.

Stratifying the rate of disease progression by Progression Likelihood Scores in children and adolescents with stage 1 and stage 2 type 1 diabetes in Germany.

Diabetes Care, DOI: 10.2337/dc25-2184 (2025)
Publ. Version/Full Text Postprint Research data DOI PMC
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OBJECTIVE: To stratify the progression rate to clinical stage 3 type 1 diabetes in children with early-stage disease. RESEARCH DESIGN AND METHODS: The Fr1da study tested 211,464 children aged 1.75-10 years for islet autoantibodies. Children with early-stage type 1 diabetes were classified as stage 1 or stage 2 by oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c) using current American Diabetes Association criteria and were followed 3-6 months. We applied our previously developed progression likelihood score (PLS), a composite of HbA1c, 90-min OGTT glucose, and islet antigen 2 antibodies (IA-2A) titer, and developed a non-OGTT-based score using multivariable Cox proportional hazards models to stratify progression rates to stage 3. RESULTS: Of 485 children who participated in staging, 360 (74.2%) were diagnosed with stage 1. Of these, stage 3 developed in 105 (median follow-up 3.3 years). PLS stratified the 2-year risk for stage 3 from 43.7% (95% CI 24.3-58.1) in children with high PLS to 4.7% (1.7-7.7) and 0% in those with intermediate or low PLS. Adding the variable obesity improved the existing model. In children with stage 2 with a single dysglycemic abnormality, PLS could stratify 2-year risk for stage 3 from 42.4% (95% CI 22.8-57.0) to 5.6% (0.0-15.6). A non-OGTT-based score based on IA-2A titer categories, HbA1c, obesity, and autoantibody positivity for IA-2 juxtamembrane epitopes could identify individuals with low (1.7%) and moderate (24.6%) 2-year risk. CONCLUSIONS: The PLS and a novel non-OGTT-based score can stratify the short- to medium-term progression rates to stage 3 and should be considered for guiding monitoring practices and clinical trial eligibility.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Publisher American Diabetes Association
Publishing Place Alexandria, Va.
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)
Grants Deutsches Zentrum för Diabetesforschung