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

On behalf of the TEDDY Study Group

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1931-1940
Number of pages10
JournalDiabetologia
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Autoimmunity
Type 1 Diabetes Mellitus
Respiratory Tract Infections
Autoantibodies
Tracheitis
Infection
Laryngitis
Common Cold
Insulinoma
Sinusitis
Proportional Hazards Models
Human Influenza
Cohort Studies
Genotype
Newborn Infant
Prospective Studies
Insulin
Viruses
Antigens

Keywords

  • Autoimmunity
  • Islet autoantibodies
  • Prospective cohort
  • Respiratory infections
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity : the TEDDY study. / On behalf of the TEDDY Study Group.

In: Diabetologia, Vol. 60, No. 10, 01.10.2017, p. 1931-1940.

Research output: Contribution to journalArticle

On behalf of the TEDDY Study Group. / Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity : the TEDDY study. In: Diabetologia. 2017 ; Vol. 60, No. 10. pp. 1931-1940.
@article{fe8d3802d70c47cea85ec35ea5acd19b,
title = "Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study",
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 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.",
keywords = "Autoimmunity, Islet autoantibodies, Prospective cohort, Respiratory infections, Type 1 diabetes",
author = "{On behalf of the TEDDY Study Group} and Maria L{\"o}nnrot and Lynch, {Kristian F.} and {Elding Larsson}, Helena and {\AA}ke Lernmark and Rewers, {Marian J.} and Carina T{\"o}rn and Burkhardt, {Brant R.} and Thomas Briese and Hagopian, {William A.} and She, {Jin Xiong} and Simell, {Olli G.} and Jorma Toppari and Ziegler, {Anette G.} and Beena Akolkar and Krischer, {Jeffrey P.} and Heikki Hy{\"o}ty",
year = "2017",
month = "10",
day = "1",
doi = "10.1007/s00125-017-4365-5",
language = "English (US)",
volume = "60",
pages = "1931--1940",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity

T2 - the TEDDY study

AU - On behalf of the TEDDY Study Group

AU - Lönnrot, Maria

AU - Lynch, Kristian F.

AU - Elding Larsson, Helena

AU - Lernmark, Åke

AU - Rewers, Marian J.

AU - Törn, Carina

AU - Burkhardt, Brant R.

AU - Briese, Thomas

AU - Hagopian, William A.

AU - She, Jin Xiong

AU - Simell, Olli G.

AU - Toppari, Jorma

AU - Ziegler, Anette G.

AU - Akolkar, Beena

AU - Krischer, Jeffrey P.

AU - Hyöty, Heikki

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - Autoimmunity

KW - Islet autoantibodies

KW - Prospective cohort

KW - Respiratory infections

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85026788502&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026788502&partnerID=8YFLogxK

U2 - 10.1007/s00125-017-4365-5

DO - 10.1007/s00125-017-4365-5

M3 - Article

C2 - 28770319

AN - SCOPUS:85026788502

VL - 60

SP - 1931

EP - 1940

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -