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
N1 - Funding Information:
Funding This study was funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955 and contract number HHSN267200700014C from the NIDDK, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), JDRF and Centers for Disease Control and Prevention (CDC). This work supported in part by National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Science Awards to the University of Florida (UL1 TR000064), the University of Colorado (UL1 TR001082) and Sigrid Juselius Foundation (grant to HH).
Funding Information:
TEDDY families are warmly acknowledged for their participation in this study. The TEDDY Study Group is acknowledged for excellent collaboration (see ESM). This study was funded by U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955 and contract number HHSN267200700014C from the NIDDK, National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), National Institute of Environmental Health Sciences (NIEHS), JDRF and Centers for Disease Control and Prevention (CDC). This work supported in part by National Institutes of Health (NIH)/National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Science Awards to the University of Florida (UL1 TR000064), the University of Colorado (UL1 TR001082) and Sigrid Juselius Foundation (grant to HH).
Publisher Copyright:
© 2017, Springer-Verlag GmbH Germany.
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
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U2 - 10.1007/s00125-017-4365-5
DO - 10.1007/s00125-017-4365-5
M3 - Article
C2 - 28770319
AN - SCOPUS:85026788502
SN - 0012-186X
VL - 60
SP - 1931
EP - 1940
JO - Diabetologia
JF - Diabetologia
IS - 10
ER -