We investigated evolution of islet autoantibodies (IAs) prior to onset of T1D from 5 large-scale birth cohort studies. Our analysis revealed three distinct IA trajectories leading up to diagnosis of T1D. Of 24673 children from five prospective studies (DAISY, DiPiS, DIPP, DEW-IT, and BABYDIAB), 688 who were diagnosed with T1D and had 3 or more visits were included in this analysis. Hidden Markov Models were developed to label visit-level observation of each subject based on three IAs: GADA, IAA, and IA-2A. Interactive visualizations were then applied to explore model outcomes, identify IA evolution trajectories, and examine their clinical characteristics. Three trajectories were identified (Figure 1) with a majority of children having multiple IA (Tr1: n=265) or IAA first (Tr2: n=282) at seroconversion; the minority seroconverted with GADA first (Tr3: n=131). The Tr3 group had seroconversion and T1D onset at an older age in months (58, 132) than Tr1 (42, 96) and Tr2 (31, 88), P < .01. Distribution of HLA DR/DQ differed between groups: higher DRX/X and lower DR3/4 in Tr3 (18%, 24%) than Tr1 (11%, 26%) and Tr2 (10%, 31%). The three IA trajectories show distinctive antibody patterns, ages of seroconversion and T1D onset and HLA DR/DQ group distributions among them. Furthermore, heterogeneity is also shown within each trajectory in terms of progression time and needs further investigation.


B. Kwon: None. P. Achenbach: None. V. Anand: None. J.L. Dunne: None. W. Hagopian: Consultant; Self; Novo Nordisk Inc. M. Lundgren: None. R. Veijola: None. B.I. Frohnert: None.


JDRF (1-IND-2019-717-I-X, 1-SRA-2019-722-I-X, 1-SRA-2019-723-I-X, 1-SRA-2019-719-I-X, 1-SRA-2019-721-I-X, 1-SRA-2019-720-I-X)

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