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Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity : the TEDDY study

Lönnrot, Maria; Lynch, Kristian F. LU ; Elding Larsson, Helena LU ; Lernmark, Åke LU ; Rewers, Marian J.; Törn, Carina LU ; Burkhardt, Brant R.; Briese, Thomas; Hagopian, William A and She, Jin-Xiong, et al. (2017) In Diabetologia 60(10). p.1931-1940
Abstract

Aims/hypothesis: Respiratory infections and onset of islet autoimmunity are reported to correlate positively in two small prospective studies. The Environmental Determinants of Diabetes in the Young (TEDDY) study is the largest prospective international cohort study on the environmental determinants of type 1 diabetes that regularly monitors both clinical infections and islet autoantibodies. The aim was to confirm the influence of reported respiratory infections and to further characterise the temporal relationship with autoantibody seroconversion. Methods: During the years 2004–2009, 8676 newborn babies with HLA genotypes conferring an increased risk of type 1 diabetes were enrolled at 3 months of age to participate in a 15 year... (More)

Aims/hypothesis: Respiratory infections and onset of islet autoimmunity are reported to correlate positively in two small prospective studies. The Environmental Determinants of Diabetes in the Young (TEDDY) study is the largest prospective international cohort study on the environmental determinants of type 1 diabetes that regularly monitors both clinical infections and islet autoantibodies. The aim was to confirm the influence of reported respiratory infections and to further characterise the temporal relationship with autoantibody seroconversion. Methods: During the years 2004–2009, 8676 newborn babies with HLA genotypes conferring an increased risk of type 1 diabetes were enrolled at 3 months of age to participate in a 15 year follow-up. In the present study, the association between parent-reported respiratory infections and islet autoantibodies at 3 month intervals up to 4 years of age was evaluated in 7869 children. Time-dependent proportional hazard models were used to assess how the timing of respiratory infections related to persistent confirmed islet autoimmunity, defined as autoantibody positivity against insulin, GAD and/or insulinoma antigen-2, concordant at two reference laboratories on two or more consecutive visits. Results: In total, 87,327 parent-reported respiratory infectious episodes were recorded while the children were under study surveillance for islet autoimmunity, and 454 children seroconverted. The number of respiratory infections occurring in a 9 month period was associated with the subsequent risk of autoimmunity (p < 0.001). For each 1/year rate increase in infections, the hazard of islet autoimmunity increased by 5.6% (95% CI 2.5%, 8.8%). The risk association was linked primarily to infections occurring in the winter (HR 1.42 [95% CI 1.16, 1.74]; p < 0.001). The types of respiratory infection independently associated with autoimmunity were common cold, influenza-like illness, sinusitis, and laryngitis/tracheitis, with HRs (95% CI) of 1.38 (1.11, 1.71), 2.37 (1.35, 4.15), 2.63 (1.22, 5.67) and 1.76 (1.04, 2.98), respectively. Conclusions/interpretation: Recent respiratory infections in young children correlate with an increased risk of islet autoimmunity in the TEDDY study. Further studies to identify the potential causative viruses with pathogen-specific assays should focus especially on the 9 month time window leading to autoantibody seroconversion.

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keywords
Autoimmunity, Islet autoantibodies, Prospective cohort, Respiratory infections, Type 1 diabetes
in
Diabetologia
volume
60
issue
10
pages
1931 - 1940
publisher
Springer Verlag
external identifiers
  • scopus:85026788502
  • wos:000408770300010
ISSN
0012-186X
DOI
10.1007/s00125-017-4365-5
language
English
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yes
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52d8d7bf-fe30-40ca-93c8-bd5e098f3601
date added to LUP
2017-08-21 10:58:51
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2018-08-12 04:38:45
@article{52d8d7bf-fe30-40ca-93c8-bd5e098f3601,
  abstract     = {<p>Aims/hypothesis: Respiratory infections and onset of islet autoimmunity are reported to correlate positively in two small prospective studies. The Environmental Determinants of Diabetes in the Young (TEDDY) study is the largest prospective international cohort study on the environmental determinants of type 1 diabetes that regularly monitors both clinical infections and islet autoantibodies. The aim was to confirm the influence of reported respiratory infections and to further characterise the temporal relationship with autoantibody seroconversion. Methods: During the years 2004–2009, 8676 newborn babies with HLA genotypes conferring an increased risk of type 1 diabetes were enrolled at 3 months of age to participate in a 15 year follow-up. In the present study, the association between parent-reported respiratory infections and islet autoantibodies at 3 month intervals up to 4 years of age was evaluated in 7869 children. Time-dependent proportional hazard models were used to assess how the timing of respiratory infections related to persistent confirmed islet autoimmunity, defined as autoantibody positivity against insulin, GAD and/or insulinoma antigen-2, concordant at two reference laboratories on two or more consecutive visits. Results: In total, 87,327 parent-reported respiratory infectious episodes were recorded while the children were under study surveillance for islet autoimmunity, and 454 children seroconverted. The number of respiratory infections occurring in a 9 month period was associated with the subsequent risk of autoimmunity (p &lt; 0.001). For each 1/year rate increase in infections, the hazard of islet autoimmunity increased by 5.6% (95% CI 2.5%, 8.8%). The risk association was linked primarily to infections occurring in the winter (HR 1.42 [95% CI 1.16, 1.74]; p &lt; 0.001). The types of respiratory infection independently associated with autoimmunity were common cold, influenza-like illness, sinusitis, and laryngitis/tracheitis, with HRs (95% CI) of 1.38 (1.11, 1.71), 2.37 (1.35, 4.15), 2.63 (1.22, 5.67) and 1.76 (1.04, 2.98), respectively. Conclusions/interpretation: Recent respiratory infections in young children correlate with an increased risk of islet autoimmunity in the TEDDY study. Further studies to identify the potential causative viruses with pathogen-specific assays should focus especially on the 9 month time window leading to autoantibody seroconversion.</p>},
  author       = {Lönnrot, Maria and Lynch, Kristian F. and Elding Larsson, Helena and Lernmark, Åke and Rewers, Marian J. and Törn, Carina and Burkhardt, Brant R. and Briese, Thomas and Hagopian, William A and She, Jin-Xiong and Simell, Olli G. and Toppari, Jorma and Ziegler, A. G. and Akolkar, Beena and Krischer, Jeffrey P. and Hyöty, Heikki and , },
  issn         = {0012-186X},
  keyword      = {Autoimmunity,Islet autoantibodies,Prospective cohort,Respiratory infections,Type 1 diabetes},
  language     = {eng},
  month        = {08},
  number       = {10},
  pages        = {1931--1940},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity : the TEDDY study},
  url          = {http://dx.doi.org/10.1007/s00125-017-4365-5},
  volume       = {60},
  year         = {2017},
}