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Frohnert, B.I.* ; Ghalwash, M.* ; Li, Y.* ; Ng, K.* ; Dunne, J.L.* ; Lundgren, M.* ; Hagopian, W.* ; Lou, O.* ; Winkler, C. ; Toppari, J.* ; Veijola, R.* ; Anand, V.*

Refining the definition of stage 1itype 1 diabetes: An ontology-driven analysis of the heterogeneity of multiple Islet autoimmunity.

Diabetes Care 46, 1753-1761 (2023)
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OBJECTIVE: To estimate the risk of progression to stage 3 type 1 diabetes based on varying definitions of multiple islet autoantibody positivity (mIA). RESEARCH DESIGN AND METHODS: Type 1 Diabetes Intelligence (T1DI) is a combined prospective data set of children from Finland, Germany, Sweden, and the U.S. who have an increased genetic risk for type 1 diabetes. Analysis included 16,709 infants-toddlers enrolled by age 2.5 years and comparison between groups using Kaplan-Meier survival analysis. RESULTS: Of 865 (5%) children with mIA, 537 (62%) progressed to type 1 diabetes. The 15-year cumulative incidence of diabetes varied from the most stringent definition (mIA/Persistent/2: two or more islet autoantibodies positive at the same visit with two or more antibodies persistent at next visit; 88% [95% CI 85-92%]) to the least stringent (mIA/Any: positivity for two islet autoantibodies without co-occurring positivity or persistence; 18% [5-40%]). Progression in mIA/Persistent/2 was significantly higher than all other groups (P < 0.0001). Intermediate stringency definitions showed intermediate risk and were significantly different than mIA/Any (P < 0.05); however, differences waned over the 2-year follow-up among those who did not subsequently reach higher stringency. Among mIA/Persistent/2 individuals with three autoantibodies, loss of one autoantibody by the 2-year follow-up was associated with accelerated progression. Age was significantly associated with time from seroconversion to mIA/Persistent/2 status and mIA to stage 3 type 1 diabetes. CONCLUSIONS: The 15-year risk of progression to type 1 diabetes risk varies markedly from 18 to 88% based on the stringency of mIA definition. While initial categorization identifies highest-risk individuals, short-term follow-up over 2 years may help stratify evolving risk, especially for those with less stringent definitions of mIA.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Beta-cell Autoimmunity; Progression; Risk; Prediction; Autoantibodies; Population; Childhood; Children; Appearance; Reversion
ISSN (print) / ISBN 0149-5992
e-ISSN 1935-5548
Journal Diabetes Care
Quellenangaben Volume: 46, Issue: 10, Pages: 1753-1761 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)
Grants Centers for Disease Control and Prevention
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health
JDRF
Washington State Life Science Discovery Fund
Hussman Foundation
Lund University Diabetes Centre Industrial Research Centre/Excellence Of Diabetes Research in Sweden (EXODIAB) from the Swedish Foundation for Strategic Research (Stiftelsen for Strategisk Forskning)
Skane County Council's Foundation for Research and Development
Royal Physiographic Society (Kungliga Fysiografiska Sallskapet i Lund)
Lions Clubs International Foundation
SUS Funds
Nordisk Insulin Fund
Swedish Diabetes Association
European Union
Swedish Research Council
German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung)
Sigrid Juseliuksen Saatio Foundation (Finland)
Diabetes Research Foundation (Finland)
Special Research Funds for University Hospitals in Finland
Centre of Excellence in Molecular Systems Immunology and Physiology Research 2012-2017
Academy of Finland
Novo Nordisk Foundation Center for Basic Metabolic Research
Swedish Childhood Diabetes Foundation