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.