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Gastrointestinal infections modulate the risk for insulin autoantibodies as the first-appearing autoantibody in the TEDDY Study

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posted on 2023-08-22, 21:48 authored by Maria Lönnrot, Kristian F. Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A. McIndoe, Jorma Toppari, Anette G. Ziegler, Joseph F. Petrosino, Richard Lloyd, Heikki Hyöty

Objective: To investigate gastrointestinal infection episodes (GIE) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

Research Design and Methods: GIE on risk of autoantibodies against either insulin (IAA) or glutamic acid decarboxylase (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7867 children. Stool virome was characterized in a nested case-control study.

Results GIE reports (OR 2.17 [1.39 – 3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36 – 23.7]) at <1 year of age associated with an increased IAA risk at 2-4 years of age. GIE reported at age 1 to <2 years correlated with a lower risk of IAA up to 10 years of age (OR 0.48 [95%CI 0.35 – 0.68]). GIE reports at any other age were associated with an increase in IAA-risk (OR 2.04 for IAA when GIE was observed 12 to 23 months prior [1.41 – 2.96]). Impacts on GADA-risk were limited to GIE <6 months prior to autoantibody development in <4 year old children (OR 2.16 [1.54 – 3.02]).

Conclusions: Bidirectional associations were observed. GIE associated with increased IAA-risk when reported before one year of age or 12-23 months prior to IAA. Norwalk virus was identified as one possible candidate factor. GIE reported during the second year of life associated with a decreased IAA-risk.

Funding

Funding The TEDDY Study is funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), Centers for Disease Control and Prevention (CDC), and JDRF. This work is supported in part by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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