Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Nov 1;46(11):1908-1915.
doi: 10.2337/dc23-0518.

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

Collaborators, Affiliations

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

Maria Lönnrot et al. Diabetes Care. .

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.

PubMed Disclaimer

Conflict of interest statement

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Age-specific incidence of IAA, GADA, and IA-2A as the first-appearing autoantibody (A) and GIEs (B).
Figure 2
Figure 2
IAA risk irrespective of age (solid horizontal line, OR [95% CI]) and by age (×, OR) when GIE was reported at <1 year of age (A), 1 to <2 years of age (B), and 2 to <3 years of age (C). Time lag correlation at 0–11 months (D) 12–23 months (E), and 24–35 months (F) between GIEs and subsequent risk of IAA-first development irrespective of age (solid horizontal line, OR [95% CI]) and at the age when children developed IAA (×, OR). Period of autoantibody development is defined as time after a scheduled blood draw visit up until the next blood draw visit when autoantibodies can be first detected.
Figure 3
Figure 3
Common viruses in stools (n = 7,202) collected monthly from 751 children 3–24 months of age and association with the odds of GIE report within ±2 weeks from stool sample collection date (A). Percentage of stool samples (B) (separate bars for virus-positive and virus-negative samples) with a reported GIE within ±2 weeks from stool sample collection date.
Figure 4
Figure 4
Common viruses (>2.5% of samples) in stools of children between 3 and 12 months of age (A and B) and 13–24 months of age (C) in relation to risk of IAA-first appearance between the 6 and 24 months of age (A) (n = 127 IAA-first case and match control pairs) and between 25 and 60 months of age (B and C) (n = 52 IAA-first case and match control pairs). Viruses in relation to IAA-first were examined separately, adjusting for HLA-DR genotype and matching factors (sex, site, and family history of T1D). Associations with P < 0.05 are shown in color. #Significant interaction between virus and age of seroconversion.

References

    1. TEDDY Study Group . The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes 2007;8:286–298 - PubMed
    1. TEDDY Study Group . The Environmental Determinants of Diabetes in the Young (TEDDY) study. Ann N Y Acad Sci 2008;1150:1–13 - PMC - PubMed
    1. Rewers M, Hyöty H, Lernmark Å, et al. .; TEDDY Study Group . The Environmental Determinants of Diabetes in the Young (TEDDY) study: 2018 update. Curr Diab Rep 2018;18:136. - PMC - PubMed
    1. Lönnrot M, Lynch K, Larsson HE, et al. .; TEDDY Study Group . A method for reporting and classifying acute infectious diseases in a prospective study of young children: TEDDY. BMC Pediatr 2015;15:24. - PMC - PubMed
    1. Lönnrot M, Lynch KF, Elding Larsson H, et al. .; TEDDY Study Group . Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study. Diabetologia 2017;60:1931–1940 - PMC - PubMed

Publication types