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Lönnrot, M.* ; Lynch, K.F.* ; Rewers, M.* ; Lernmark, * ; Vehik, K.* ; Akolkar, B.* ; Hagopian, W.* ; Krischer, J.* ; McIndoe, R.A.* ; Toppari, J.* ; Ziegler, A.-G. ; Petrosino, J.F.* ; Lloyd, R.* ; Hyoty, H.* ; TEDDY Study Group (Gezginci, C. ; Heublein, A. ; Hummel, S. ; Knopff, A. ; Köger, M. ; Koletzko, S. ; Roth, R. ; Schmidt, J. ; Scholz, M. ; Stock, J. ; Warncke, K. ; Wendel, L. ; Winkler, C.)

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

Diabetes Care 46, 1908-1915 (2023)

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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.

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