Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories

Bum Chul Kwon (), Vibha Anand, Peter Achenbach, Jessica L. Dunne, William Hagopian, Jianying Hu, Eileen Koski, Åke Lernmark, Markus Lundgren, Kenney Ng, Jorma Toppari, Riitta Veijola and Brigitte I. Frohnert
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Bum Chul Kwon: IBM Research
Vibha Anand: IBM Research
Peter Achenbach: German Research Center for Environmental Health
Jessica L. Dunne: JDRF
William Hagopian: Pacific Northwest Research Institute
Jianying Hu: Center for Computational Health, IBM Research
Eileen Koski: Center for Computational Health, IBM Research
Åke Lernmark: Skåne University Hospital
Markus Lundgren: Skåne University Hospital
Kenney Ng: IBM Research
Jorma Toppari: Turku University Hospital
Riitta Veijola: University of Oulu and Oulu University Hospital, Department of Pediatrics, PEDEGO Research Unit
Brigitte I. Frohnert: University of Colorado

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study. Our Continuous-Time Hidden Markov Models, that are developed to discover and visualize latent states based on the collected data and clinical characteristics of the patients, show that the health state of participants progresses from 11 distinct latent states as per three trajectories (TR1, TR2 and TR3), with associated 5-year cumulative diabetes-free survival of 40% (95% confidence interval [CI], 35% to 47%), 62% (95% CI, 57% to 67%), and 88% (95% CI, 85% to 91%), respectively (p

Date: 2022
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DOI: 10.1038/s41467-022-28909-1

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