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

Author

Listed:
  • 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)

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

Suggested Citation

  • 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 & Brigitt, 2022. "Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28909-1
    DOI: 10.1038/s41467-022-28909-1
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    References listed on IDEAS

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    1. Claeskens,Gerda & Hjort,Nils Lid, 2008. "Model Selection and Model Averaging," Cambridge Books, Cambridge University Press, number 9780521852258.
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