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

Lönnrot, Maria ; Lynch, Kristian F LU ; Rewers, Marian ; Lernmark, Åke LU orcid ; Vehik, Kendra LU ; Akolkar, Beena ; Hagopian, William ; Krischer, Jeffrey ; McIndoe, Rickhard A and Toppari, Jorma , et al. (2023) In Diabetes Care 46(11). p.1908-1915
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... (More)

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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author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
46
issue
11
pages
1908 - 1915
publisher
American Diabetes Association
external identifiers
  • scopus:85175355699
  • pmid:37607456
ISSN
1935-5548
DOI
10.2337/dc23-0518
language
English
LU publication?
yes
additional info
© 2023 by the American Diabetes Association.
id
cf43fa65-3cad-4610-8c10-ec7393c79299
date added to LUP
2023-08-24 09:08:09
date last changed
2024-09-21 23:10:27
@article{cf43fa65-3cad-4610-8c10-ec7393c79299,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &lt;1 year of age were associated with an increased IAA risk at 2-4 years of age. GIEs reported at age 1 to &lt;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 &lt;6 months prior to autoantibody development in children &lt;4 years of age (OR 2.16 [1.54-3.02]).</p><p>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.</p>}},
  author       = {{Lönnrot, Maria and Lynch, Kristian F and Rewers, Marian and Lernmark, Åke and Vehik, Kendra and Akolkar, Beena and Hagopian, William and Krischer, Jeffrey and McIndoe, Rickhard A and Toppari, Jorma and Ziegler, Anette-G and Petrosino, Joseph F and Lloyd, Richard and Hyöty, Heikki}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{11}},
  pages        = {{1908--1915}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study}},
  url          = {{http://dx.doi.org/10.2337/dc23-0518}},
  doi          = {{10.2337/dc23-0518}},
  volume       = {{46}},
  year         = {{2023}},
}