{"doi":"10.2337/dc25-2184","title":"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","abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE</jats:title>\n                    <jats:p>To stratify the progression rate to clinical stage 3 type 1 diabetes in children with early-stage disease.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>","journal":"Diabetes Care","year":2026,"id":630203,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1632476,"name":"Lenche Chakievska","orcid":null,"position":1,"is_corresponding":false},{"id":96909,"name":"Peter Achenbach","orcid":"0000-0001-6720-2684","position":2,"is_corresponding":false},{"id":1632478,"name":"Maja Hergl","orcid":null,"position":3,"is_corresponding":false},{"id":71709,"name":"Sandra Hummel","orcid":"0000-0001-6554-5974","position":4,"is_corresponding":false},{"id":1557474,"name":"Raffael Ott","orcid":"0000-0002-5178-1033","position":5,"is_corresponding":false},{"id":1632479,"name":"Marlon Scholz","orcid":null,"position":6,"is_corresponding":false},{"id":60967,"name":"Christiane Winkler","orcid":"0000-0002-7606-3687","position":7,"is_corresponding":false},{"id":28468,"name":"Ezio Bonifacio","orcid":"0000-0002-8704-4713","position":8,"is_corresponding":false},{"id":60971,"name":"Anette‐Gabriele Ziegler","orcid":"0000-0002-6290-5548","position":9,"is_corresponding":false},{"id":141785,"name":"Andreas Weiss","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"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.","abstract":"<h4>Objective</h4>To stratify the progression rate to clinical stage 3 type 1 diabetes in children with early-stage disease.<h4>Research design and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41401417","pmcid":"PMC12824801","openalex_id":null,"authors":[],"funders":[{"funder_name":"LifeScience Stiftung","grant_id":"HMGU 2014.01, HMGU 2016.01","title":null},{"funder_name":"Leona M. and Harry B. Helmsley Charitable Trust","grant_id":"G-1911-3274","title":null},{"funder_name":"Breakthrough T1D","grant_id":"1-SRA-2014-310-M-R, 3-SRA-2019-718-Q-R, 3-SRA-2015","title":null},{"funder_name":"Deutsche Diabetiker Bund e.V. and the Innovative Health Initiative Joint Undertaking","grant_id":"101132379","title":null},{"funder_name":"Deutsches Zentrum for Diabetesforschung","grant_id":"","title":null}],"total_grants":5,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://diabetesjournals.org/care/article-pdf/doi/10.2337/dc25-2184/851816/dc252184.pdf","host_type":"publisher"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12824801/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12824801","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12824801?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Humans","Diabetes Mellitus, Type 1","Disease Progression","Autoantibodies","Glucose Tolerance Test","Adolescent","Child","Child, Preschool","Infant","Germany","Female","Male","Glycated Hemoglobin"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T20:40:02.489165Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}