Ambient Air Pollution and Early Manifestation of Type 1 Diabetes

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, https://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, https://links.lww.com/EDE/A875).FIGURE: Point estimates and 95% confidence intervals for differences in the age at diagnosis of type 1 diabetes (T1D) per 2 SD increases in PM10, NO2, NDVI, PM2.5, and PM2.5 absorbance, and per 500 m increase in distance to the nearest major road, with adjustment for sex, parental education, family history of T1D, and body mass index. The dots represent specific quantile regression estimates and are connected by dashes to visualise trends by age quantiles. The horizontal grey lines represent the linear regression coefficients and their respective confidence intervals. The horizontal line depicts y = 0 as a reference.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. 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, https://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 [email protected]