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Ambient Air Pollution and Early Manifestation of Type 1 Diabetes

Beyerlein, Andreas; Krasmann, Miriam; Thiering, Elisabeth; Kusian, Dennis; Markevych, Iana; D’Orlando, Orietta; Warncke, Katharina; Jochner, Susanne; Heinrich, Joachim; Ziegler, Anette-Gabriele

doi: 10.1097/EDE.0000000000000254
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Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany

Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany

Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany

Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany

Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany

Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

Department of Ecology and Ecosystem Management Ecoclimatology, Technische Universität München, Freising, Germany

Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany

Institute of Diabetes Research, Helmholtz Zentrum München and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Neuherberg, Germany, anette-g.ziegler@helmholtz-muenchen.de

DiMelli was supported by the Competence Network Diabetes Mellitus, Federal Ministry of Education and Research (FKZ 01GI0805) from 2008 to 2012, and has been supported by the German Center for Diabetes Research (DZD) since 2012.

Joachim Heinrich and Anette-Gabriele Ziegler are joint senior authors.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com). This content is not peer-reviewed or copy-edited; it is the sole responsibility of the authors.

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To the Editor:

The incidence of type 1 diabetes (T1D) is increasing worldwide, especially in children ages 0–4 years, decreasing the mean age at diagnosis.1 Several environmental risk factors for T1D-related islet autoimmunity have been identified, including exposure to respiratory infections in very early life.2 In young children, ambient air pollution may exacerbate inflammation and promote respiratory diseases.3,4 We hypothesized that exposure to high levels of ambient air pollution is associated with earlier onset of T1D.

We analyzed data of DiMelli, a population-based register monitoring incident diabetes in children and youths in Bavaria, Germany, since 2009.5 At the registration of each patient, a structured questionnaire is completed by the attending physician, and a blood sample is drawn, which is used to determine islet autoantibodies to insulin, glutamic acid decarboxylase, IA-2, or ZnT8. Here, we used data for 671 patients registered up to May 2013 (mean age at diagnosis: 9.6 years) who were positive for at least 1 islet autoantibody and whose residential addresses were available from the questionnaire.

The concentrations of particulate matter with an aerodynamic diameter of <10 μm (PM10), nitrogen dioxide (NO2), PM2.5 and PM2.5 absorbance, normalized difference vegetation index (NDVI) as a measure of greenness, and distance to the nearest major at the residential addresses of patients were obtained from various sources (see online Supplementary material, http://links.lww.com/EDE/A875). These served as possible explanatory variables in linear regression and quantile regression6 models using the 10th, 30th, 50th (median), 70th, and 90th percentiles of age at diagnosis as the dependent variables. Models were adjusted for sex, parental education, family history of T1D, and patient’s body mass index at diagnosis, and additionally for level of urbanization in sensitivity analyses.

Exposure to high levels of PM10 and NO2 was associated with a shift in the 10th percentile of the age at diagnosis to lower values (−1.40 [95% confidence interval {CI}: −2.24, −0.56] years per 2 SD increase in PM10; −1.28 [95% CI: −2.14, −0.42] years per 2 SD increase in NO2), but not for higher percentiles or for the mean age at diagnosis (Figure 1). Considering that the 10th percentile of the age at diagnosis was 3.29 years in the whole dataset, the first 10% of children with high exposure (+2 SDs) to PM10 were predicted to develop T1D by the age of 1.89 years (ie, 3.29−1.40), whereas the 10th percentile in children with low exposure (−2 SDs) was estimated to be 4.69 years (ie, 3.29 + 1.40). No clear associations were observed for PM2.5, PM2.5 absorbance, NDVI, or the distance to the nearest major road. If we included the level of urbanization as an additional confounder, similar results were obtained, except for the association between PM2.5 and the 10th percentile of age at diagnosis (−1.37 [95% CI: −1.97, −0.77] per 2 SD increase). Boxplots of the inflammatory markers interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor indicated no clear associations with manifestation age and PM10 exposure level (Supplementary Figure, http://links.lww.com/EDE/A875).

FIGURE

FIGURE

Our findings indicate that high exposure to the traffic-related air pollutants PM10, NO2 and possibly PM2.5 accelerates the manifestation of T1D, but only in very young children. Interestingly, findings from a previous study suggested that PM10 was associated with an increased risk of T1D in children ages < 5 years.7 Our results were independent of urbanization level, indicating that air pollutants, not urbanization-related lifestyle habits or for example higher temperatures in urbanized areas, might be responsible for the observed associations. However, we did not observe any clear associations with inflammatory markers to show that air pollution accelerates the onset of T1D by inducing a more severe inflammatory state in young children.

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ACKNOWLEDGEMENTS

We thank Ramona Puff, Anja Wosch, Kathrin Hofer, Claudia Matzke, Marlon Scholz, Vanessa Dietrich, and Petra Becker (Institute of Diabetes Re search, Helmholtz Zentrum München) for their contributions to registry coordination, patient recruitment, data management, and expert technical assistance. We also thank all of the participating clinics and investigators for their support in recruiting participants in DiMelli. A list of the main participating clinics can be found in the online Supplementary material, http://links.lww.com/EDE/A875.

Andreas Beyerlein

Miriam Krasmann

Institute of Diabetes Research

Helmholtz Zentrum München and

Forschergruppe Diabetes

Klinikum rechts der Isar

Technische Universität München

Neuherberg, Germany

Elisabeth Thiering

Institute of Epidemiology I

Helmholtz Zentrum München

Neuherberg, Germany

Dennis Kusian

Institute of Diabetes Research

Helmholtz Zentrum München and

Forschergruppe Diabetes

Klinikum rechts der Isar

Technische Universität München

Neuherberg, Germany

Iana Markevych

Institute of Epidemiology I

Helmholtz Zentrum München

Neuherberg, Germany

Orietta D’Orlando

Institute of Diabetes Research

Helmholtz Zentrum München and

Forschergruppe Diabetes

Klinikum rechts der Isar

Technische Universität München

Neuherberg, Germany

Katharina Warncke

Department of Pediatrics

Klinikum rechts der Isar

Technische Universität München

Munich, Germany

Susanne Jochner

Department of Ecology and

Ecosystem Management Ecoclimatology

Technische Universität München

Freising, Germany

Joachim Heinrich

Institute of Epidemiology I

Helmholtz Zentrum München

Neuherberg, Germany

Anette-Gabriele Ziegler

Institute of Diabetes Research

Helmholtz Zentrum München and

Forschergruppe Diabetes

Klinikum rechts der Isar

Technische Universität München

Neuherberg, Germany

anette-g.ziegler@helmholtz-muenchen.de

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REFERENCES

1. Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G, Group ES. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033
2. Beyerlein A, Wehweck F, Ziegler AG, Pflueger M. Respiratory infections in early life and the development of islet autoimmunity in children at increased type 1 diabetes risk: evidence from the BABYDIET study. JAMA Pediatr. 2013;167:800–807
3. Li Y, Rittenhouse-Olson K, Scheider WL, Mu L. Effect of particulate matter air pollution on C-reactive protein: a review of epidemiologic studies. Rev Environ Health. 2012;27:133–149
4. MacIntyre EA, Gehring U, Molter A, et al. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE Project. Environ Health Perspect. 2014;122:107–113
5. Thümer L, Adler K, Bonifacio E. German new onset diabetes in the young incident cohort study: DiMelli study design and first-year results. Rev Diabet Stud. 2010;7:202–208
6. Beyerlein A. Quantile regression: opportunities and challenges from a user’s perspective. Am J Epidemiol. 2014;180:330–331
7. Hathout EH, Beeson WL, Nahab F, Rabadi A, Thomas W, Mace JW. Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age. Pediatr Diabetes. 2002;3:184–188

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