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Re: Ambient Air Pollution and Early Manifestation of Type 1 Diabetes

Rosenbauer, Joachim; Tamayo, Teresa; Bächle, Christina; Stahl-Pehe, Anna; Landwehr, Sandra; Sugiri, Dorothee; Krämer, Ursula; Maier, Werner; Hermann, Julia M.; Holl, Reinhard W.; Rathmann, Wolfgang

doi: 10.1097/EDE.0000000000000495
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Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany, German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany, joachim.rosenbauer@ddz.uni-duesseldorf.de

Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany, Institute of Medical Statistics, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany

Helmholtz Zentrum München, Institute of Health Economics and Health Care Management, Neuherberg, Germany, German Center for Diabetes Research (DZD), Partner Neuherberg, Neuherberg, Germany

Institute for Epidemiology and Medical Biometry, ZIBMT, University of Ulm, Ulm, Germany, German Center for Diabetes Research (DZD), Associated Partner Ulm, Ulm, Germany

Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany, German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany

Supported by the Competence Network for Diabetes Mellitus funded by the Federal Ministry of Education and Research (Support Code 01GI1109A), which has been integrated into the German Center for Diabetes Research (DZD) as of January 2015. The German Diabetes Center is institutionally funded by the German Ministry of Health and the Ministry of Innovation, Sciences and Research of the Federal State of North Rhine-Westphalia.

The authors report no conflicts of interest.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article (www.epidem.com).

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To the Editor

Animal and epidemiologic studies suggest adverse effects of ambient air pollutants on type 1 diabetes.1–4 Increased pre- or postnatal exposure to air pollutants (ozone, particulate matter, sulfate, and nitrogen dioxide) was shown to be associated with an increased type 1 diabetes risk, and particulate matter to type 1 diabetes onset before 5 years old.2–4 However, findings regarding single air pollutants have been inconsistent. A recent study indicated that traffic-related air pollution may accelerate the manifestation of type 1 diabetes in very young children.5

We analyzed the association between air pollutants and age at onset of type 1 diabetes using data from the type 1 diabetes register for North Rhine-Westphalia (West-Germany), which is part of the EURODIAB (Europe and Diabetes) initiative.6 The completeness of registration in the age group 0–19 years was estimated to be 98% in 2002–2014. We obtained data on exposure to particulate matter with an aerodynamic diameter smaller than 10 μm (PM10), nitrogen dioxides (NO2), and accumulated ozone (O3-AOT40: excess ozone accumulated over a threshold of 40 ppb) for 2001–2005 from the German Federal Environment Agency (Umweltbundesamt II). Smoothed exposure data are estimated based on an 8 × 8 square km grid (see eAppendix; http://links.lww.com/EDE/B50). Average concentrations were calculated for each five-digit postcode area by intersection of the 8 × 8 square km grid with the German postcode map. We determined exposure of incident cases to air pollutants by linking exposure data to cases’ residential addresses at type 1 diabetes onset according to five-digit postcodes. The ethical review board of Düsseldorf University approved the study.

We included 6,807 incident type 1 diabetes patients aged 0 to 19 years at diagnosis (mean age at diagnosis [SD]: 9.7 [4.5] years) in 2006–2014 in the principal analyses. To be consistent with a previous study,5 we applied simple linear and quantile regression with age at diagnosis and 10th, 30th, 50th, 70th, and 90th percentile as dependent and air pollutants as independent variables. Models were adjusted for sex, German versus non-German nationality, the German Index of Multiple Deprivation,7 family history of type 1 diabetes, level of urbanization of residence (Eurostat definition8), and additionally for patients’ body mass index at diagnosis (available for 5,625 cases). For sensitivity analyses, we performed quantile regressions at a finer grid of percentiles (5th to 95th percentile by 5%) and refitted all models including all incident cases in 2002–2014 from the North Rhine-Westphalia register (N = 9,722, mean age at diagnosis [SD]: 9.7 [4.5] years) and exposure data for 2001–2009.

Results indicate that exposure to ambient air pollutants or ozone was not associated either with mean age at diagnosis or with any percentile of age at diagnosis, as evident from 95% confidence interval estimates (Figure). All sensitivity analyses confirmed these results (eFigures 1–3; http://links.lww.com/EDE/B50).

FIGURE

FIGURE

Our findings indicate that high exposure to traffic-related air pollutants or atmospheric ozone on scale of several kilometers are not related to the age at onset of type 1 diabetes. Thus, our study could not provide further evidence for the recently raised hypothesis that traffic-related air pollution may accelerate the manifestation of type 1 diabetes in very young children.5

Compared with the previous study,5 shortcomings of our study that may have biased our findings are the limited spatial resolution of exposure measures (8 × 8 vs. 1 × 1 square km), the coarser linkage of exposure data to patients (five-digit postcode area of residence vs. exact residential address), and the lack of individual socioeconomic data. We, however, adjusted for community-based German index of multiple deprivation as proxy for individual socioeconomic status. Strengths of our study are the high completeness of registered type 1 diabetes cases and the large study cohort.

Given the limited and contradictory evidence, further studies from other regions, ideally prospective studies with improved measures of individual exposure to ambient air pollutants, are warranted to clarify the association of ambient air pollutants with accelerated manifestation and risk of type 1 diabetes.

Joachim Rosenbauer

Teresa Tamayo

Christina Bächle

Anna Stahl-Pehe

Institute for Biometrics and Epidemiology

German Diabetes Center

Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf

Düsseldorf, Germany

German Center for Diabetes Research (DZD)

Partner Düsseldorf

Düsseldorf, Germany

joachim.rosenbauer@ddz.uni-duesseldorf.de

Sandra Landwehr

Institute for Biometrics and Epidemiology

German Diabetes Center

Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf

Düsseldorf, Germany

Institute of Medical Statistics

Heinrich Heine University Düsseldorf

Düsseldorf, Germany

Dorothee Sugiri

Ursula Krämer

IUF-Leibniz Research Institute for Environmental Medicine

Düsseldorf, Germany

Werner Maier

Helmholtz Zentrum München

Institute of Health Economics and Health Care Management

Neuherberg, Germany

German Center for Diabetes Research (DZD)

Partner Neuherberg

Neuherberg, Germany

Julia M. Hermann

Reinhard W. Holl

Institute for Epidemiology and Medical Biometry

ZIBMT, University of Ulm

Ulm, Germany

German Center for Diabetes Research (DZD)

Associated Partner Ulm

Ulm, Germany

Wolfgang Rathmann

Institute for Biometrics and Epidemiology

German Diabetes Center

Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf

Düsseldorf, Germany

German Center for Diabetes Research (DZD)

Partner Düsseldorf

Düsseldorf, Germany

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REFERENCES

1. Yan YH, C-K Chou C, Wang JS, et al. Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model. Toxicol Appl Pharmacol. 2014;281:211–220.
2. 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.
3. Hathout EH, Beeson WL, Ischander M, Rao R, Mace JW. Air pollution and type 1 diabetes in children. Pediatr Diabetes. 2006;7:81–87.
4. Malmqvist E, Larsson HE, Jönsson I, et al. Maternal exposure to air pollution and type 1 diabetes–accounting for genetic factors. Environ Res. 2015;140:268–274.
5. Beyerlein A, Krasmann M, Thiering E, et al. Ambient air pollution and early manifestation of type 1 diabetes. Epidemiology. 2015;26:e31–e32.
6. Bendas A, Rothe U, Kiess W, et al. Trends in incidence rates during 1999-2008 and prevalence in 2008 of childhood type 1 diabetes mellitus in Germany–model-based national estimates. PLoS One. 2015;10:e0132716.
7. Maier W, Holle R, Hunger M, et al.; DIAB-CORE Consortium. The impact of regional deprivation and individual socio-economic status on the prevalence of Type 2 diabetes in Germany. A pooled analysis of five population-based studies. Diabet Med. 2013;30:e78–e86.
8. Eurostat, Reference And Management Of Nomenclatures – Degree of Urbanization. Available at http://ec.europa.eu/eurostat/ramon/miscellaneous/index.cfm?TargetUrl=DSP_DEGURBA. Accessed 6 July 2015.

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