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Diabetologia. 2017 Oct;60(10):1931-1940. doi: 10.1007/s00125-017-4365-5. Epub 2017 Aug 2.

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

Author information

1
Department of Dermatology, Tampere University Hospital, Teiskontie 35, 33521, Tampere, Finland. maria.lonnrot@uta.fi.
2
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. maria.lonnrot@uta.fi.
3
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
4
Department of Clinical Sciences Malmö, Clinical Research Centre (CRC), Lund University, Malmö, Sweden.
5
Skåne University Hospital (SUS), Malmo, Sweden.
6
Department of Clinical Sciences Malmö, Lund University Clinical Research Centre (CRC), Malmö, Sweden.
7
Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA.
8
Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
9
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
10
Pacific Northwest Diabetes Research Institute, Seattle, WA, USA.
11
Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
12
Research Centre of Applied and Preventive Cardiovascular Medicine, Faculty of Medicine, University of Turku, Turku, Finland.
13
Department of Paediatrics and Adolescent Medicine, Faculty of Medicine, University of Turku, Turku, Finland.
14
Department of Physiology, Institute of Biomedicine, University of Turku, Turku, Finland.
15
Department of Paediatrics, Turku University Hospital, Turku, Finland.
16
Forschergruppe Diabetes e.V, Neuherberg, Germany.
17
Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany.
18
National Institute of Diabetes & Digestive & Kidney Diseases, Bethesda, MD, USA.
19
Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
20
Fimlab Laboratories, Pirkanmaa Hospital District, Tampere, Finland.

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

PMID:
28770319
PMCID:
PMC5697762
DOI:
10.1007/s00125-017-4365-5
[Indexed for MEDLINE]
Free PMC Article

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