Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study - UTU Research Portal

A1 Refereed original research article in a scientific journal

Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study

Authors: Lönnrot M, Lynch KF, Rewers M, Lernmark Å, Vehik K, Akolkar B, Hagopian W, Krischer J, McIndoe RA, Toppari J, Ziegler AG, Petrosino JF, Lloyd R, Hyöty H; TEDDY Study Group

Publisher: American Diabetes Association

Publication year: 2023

Journal: Diabetes Care

Journal name in source: Diabetes care

Journal acronym: Diabetes Care

Volume: 46

Issue: 11

First page : 1908

Last page: 1915

ISSN: 0149-5992

eISSN: 1935-5548

DOI: https://doi.org/10.2337/dc23-0518

Web address : https://doi.org/10.2337/dc23-0518

Abstract

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

Research design and methods: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

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

Conclusions: Bidirectional associations were observed. GIEs were associated with increased IAA risk when reported before 1 year of age or 12-23 months prior to IAA. Norwalk virus was identified as one possible candidate factor. GIEs reported during the 2nd year of life were associated with a decreased IAA risk.