American Diabetes Association
MO2_Rev_Supplemental Appendix_Rev2[AU].pdf (1.08 MB)

Refining the Definition of Stage 1 Type 1 Diabetes: An Ontology-Driven Analysis of the Heterogeneity of Multiple Islet Autoimmunity

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posted on 2023-03-01, 19:52 authored by Brigitte I. Frohnert, Mohamed Ghalwash, Ying LiYing Li, Kenney Ng, Jessica L. Dunne, Markus Lundgren, William Hagopian, Olivia Lou, Christiane Winkler, Jorma Toppari, Riitta Veijola, Vibha Anand, the T1DI Study Group


OBJECTIVE: To estimate risk of progression to stage 3 type 1 diabetes based on varying definition of multiple islet autoantibody positivity (mIA). 

RESEARCH DESIGN AND METHODS: T1DI is a combined prospective dataset of children from Finland, Germany, Sweden and USA who are at 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%) with mIA, 537 (62%) progressed to type 1 diabetes. The 15-year cumulative incidence of diabetes varied from most stringent definition (mIA/Persistent/2: ≥2 islet autoantibodies positive at the same visit with ≥2 antibodies persistent at next visit; 88%, [95% CI: 85-92%]) to 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 from mIA/Any (p<0.05); however, differences waned over 2-year follow-up among those who did not subsequently reach higher stringency. Among mIA/Persistent/2 individuals with 3 autoantibodies, loss of one autoantibody by 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 18-88% based on 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.


Academy of Finland 250114 292538

Bundesministerium für Bildung und Forschung

U.S. Department of Health and Human Services > Centers for Disease Control and Prevention UR6/CCU017247

Deutsches Zentrum für Diabetesforschung

Hussman Foundation

JDRF 1-IND-2019-717-I-X 1-RSC-2017-368-I-X 1-RSC-2017-516-I-X 1-RSC-2017-517-I-X 1-RSC-2017-526-I-X 1-RSC-2018-555-I-X 1-SRA-2016-342-M-R 1-SRA-2019-719-I-X 1-SRA-2019-720-I-X 1-SRA-2019-722-I-X 1-SRA-2019-732-M-B 5-ECR-2017-388-A-N

Kungliga Fysiografiska Sällskapet i Lund

Lions Clubs International Foundation

U.S. Department of Health and Human Services > National Institutes of Health > National Institute of Diabetes and Digestive and Kidney Diseases DK032083 DK032493 DK104351 DK116073 DK26190

Novo Nordisk Foundation Center for Basic Metabolic Research

Sigrid Juséliuksen Säätiö

Skåne County Council's Research and Development Foundation

Stiftelsen för Strategisk Forskning Dnr IRC15-067


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