Research Traffic-Related Air Pollution and Incident Type 2 Diabetes: Results from the SALIA Cohort Study Ursula Krämer,1* Christian Herder,2* Dorothea Sugiri,1 Klaus Strassburger,3 Tamara Schikowski,1 Ulrich Ranft,1 and Wolfgang Rathmann 3 1Institut für Umweltmedizinische Forschung (IUF), Leibniz Center at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; 2Institute for Clinical Diabetology, and 3Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany o Bjectiv diabetes. Background : Cross-sectional and ecological studies indicate that air pollution may be a risk factor for type 2 diabetes, but prospective data are lacking. : We examined the association between traffic-related air pollution and incident type 2 d esign : Between 1985 and 1994, cross-sectional surveys were performed in the highly industrial- ized Ruhr district (West Germany); a follow-up investigation was conducted in 2006 using data from the Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort. p articpns : 1,775 nondiabetic women who were 54–55 years old at baseline participated in both baseline and follow-up investigations and had complete information available. Materils and Methods : Using questionnaires, we assessed 16-year incidence (1990–2006) of type 2 diabetes and information about covariates. Complement factor C3c as marker for subclinical inflammation was measured at baseline. Individual exposure to traffic-related particulate matter (PM) and nitrogen dioxide was determined at different spatial scales. r esult : Between 1990 and 2006, 87 (10.5%) new cases of diabetes were reported among the SALIA cohort members. The hazards for diabetes were increased by 15–42% per interquartile range of PM or traffic-related exposure. The associations persisted when different spatial scales were used to assess exposure and remained robust after adjusting for age, body mass index, socioeconomic status, and exposure to several non–traffic-related sources of air pollution. C3c was associated with PM pollution at baseline and was a strong independent predictor of incident diabetes. Exploratory analyses indicated that women with high C3c blood levels were more susceptible for PM-related excess risk of diabetes than were women with low C3c levels. c onclusi : Traffic-related air pollution is associated with incident type 2 diabetes among elderly women. Subclinical inflammation may be a mechanism linking air pollution with type 2 diabetes. r elvanc to clina practie : Our study identifies traffic-related air pollution as a novel and potentially modifiable risk factor of type 2 diabetes. k ey words : air pollution, cohort study, inflammation, traffic, type 2 diabetes. Environ Health Perspect 118:1273–1279 (2010). doi:10.1289/ehp.0901689 [Online 27 May 2010] Particulate matter (PM) air pollution is associated with an increased risk for cardio- vascular events (Miller et al. 2007; Pope et al. 2004). There is compelling evidence that peo- ple with diabetes are more vulnerable to car- diovascular health effects associated with PM air pollution (O’Neill et al. 2005; Whitsel et al. 2009). Findings from a study conducted by Brook et al. (2008) have suggested that several of the biological pathways that have been linked to air pollution and cardiovas- cular disease (including systemic oxidative stress and low-grade inflammation) may also promote type 2 diabetes. Recently, a cross-sectional study indicated higher diabetes prevalence among women who were exposed to higher levels of nitrogen dioxide (NO2), a marker of traffic-related air pollution (Brook et al. 2008). Another recent study demonstrated that ambient fine PM induces insulin resistance and an increase in visceral adiposity in mice (Sun et al. 2009). Subclinical inflammation has been postu- lated as a mediator between air pollution and cardiometabolic risk and has also been linked with impaired glucose metabolism (Kempf et al. 2008; Kolb and Mandrup-Poulsen 2005). Thus, an association between air pol- lution and type 2 diabetes appears conceiv- able and is biologically plausible. However, data from prospective studies on air pollution and incident type 2 diabetes are lacking. We investigated the association between traffic-related air pollution and incident type 2 diabetes in the prospective Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort study of middle-aged women in Germany (Gehring et al. 2006; Schikowski et al. 2005, 2007). We focused on traffic-related air pollution, because it represents a major source of air pollution, particularly in urban areas. SALIA comprises female participants from the highly industrial- ized Ruhr district and two rural reference coun- ties and has been used before to demonstrate associations between traffic-related air pollution and mortality and respiratory diseases (Gehring et al. 2006; Schikowski et al. 2005, 2007). Environmental Health Perspectives • volume 118 | number 9 | September 2010 Furthermore, we investigated whether subclinical inflammation might influence susceptibility to traffic-related air pollution and tested whether the association between air pollution and diabetes might depend on elevated serum concentrations of complement factor C3c at baseline. C3c is a cleavage prod- uct of the complement factor C3, one of the most abundant complement proteins in the circulatory system. C3 is produced mainly in the liver, and systemic levels increase in infection and inflammation, although to a lesser extent than acute-phase proteins such as C-reactive protein (Moshage 1997; Ritchie et al. 2004). High levels of C3 in the circu- lation are found in obesity and have been implicated in the risk for cardiovascular disease (Engström et al. 2007; Hernández- Mijares et al. 2007). C3c represents a surro- gate marker for subclinical inflammation and has been shown to be a risk factor for diabetes Address correspondence to W. Rathmann, Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf´m Hennekamp 65, D-40225 Düsseldorf, Germany. Telephone: 49 211 3382 663. Fax: 49 211 3382 677. E-mail: rathmann@ddz.uni-duesseldorf.de *These authors contributed equally to this study. Supplemental Material is available online (doi:10.1289/ehp.0901689 via http://dx.doi.org/). We thank U. Gehring (Helmholtz Zentrum München, Institute of Epidemiology, Neuherberg, Germany) for geocoding the addresses in the frame of the mortality follow-up; A. Brandt (North Rhine-Westphalia State Environmental Agency, Essen, Germany) for providing data on road traf- fic and emission inventories; T. Kuhlbusch (IUTA Duisburg Institut für Energie- und Umwelttechnik e.V., Duisburg, Germany) for conducting the measurement program for particles and NO2; K. Meliefste (Institute for Risk Assessment Sciences, Utrecht University, The Netherlands) for analyzing the blackness of particle filters; the German Remote Sensing Data Center, Wessling, Germany, for pro- viding the land-use data; and R. Stiller-Winkler, B. Schulten, H. Idel (Hygiene Institute of the University Düsseldorf, Germany) for analyzing C3c in the base- line investigation. Finally, we express our apprecia- tion to all study participants. This study was supported by the Ministries of the Environment and of Innovation, Science, Research and Technology (North-Rhine Westphalia) and the German Federal Ministry of Health. The authors declare they have no actual or potential competing financial interests. Received 13 November 2009; accepted 11 May 2010. 1273