Krämer et al. (Shima et al. 1999). It was measured at study baseline and showed an association with air pollution (Stiller-Winkler et al. 1989). Materials and Methods Study design and population. The SALIA cohort study is based on consecutive cross- sectional surveys that were performed between 1985 and 1994 as part of the Environmental Health surveys in North-Rhine Westphalia (West Germany). Seven different study areas from the highly industrialized Ruhr district [Dortmund (1985, 1990), Duisburg (1990), Essen (1990), Gelsenkirchen (1986, 1990), and Herne (1986)] were chosen to represent a range of polluted areas with high-traffic load as well as steel and coal industries. Additionally two nearby nonindustrialized towns [Borken (1985, 1986, 1987, 1990, 1993, 1994) and Dülmen (1985, 1986)] were chosen as lower polluted areas. All women 54–55 years old who were living in the study region were asked to participate; a total of 4,874 women (70%) participated in the study (Schikowski et al. 2005). Gehring et al. (2006) conducted a mortality follow-up of these women in 2003. In 2006, we performed a questionnaire follow-up and invited all women who were still living and who had addresses available (n = 4,027). A follow-up clinical examina- tion in a randomly selected subgroup was per- formed in 2008–2009. We obtained written informed consent from all study participants. The study was approved by the ethics com- mittee of the Ruhr University in Bochum (Germany). Baseline examination. The baseline ques- tionnaire included items on symptoms and diagnoses of respiratory diseases [Fragebogen der Querschnittstudie 55jähriger Frauen (Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein- Westfalen 1993)]. We also asked about single-room heating with fossil fuels and occupational exposure (dust and extreme tem- peratures). Socioeconomic status was stratified into two categories by the maximum period of education achieved by either the women or their husbands (< 10 years vs. ≥ 10 years). Women were also grouped according to their smoking habits as never smokers, passive smokers (home, workplace), past smokers, or current smokers (further categorized by < 15, 15–30, and > 30 pack-years). Height and weight were measured under standardized conditions. Nonfasting serum samples were collected and stored in the central laboratory at the Hygiene Institute (Düsseldorf University, Germany) at –70°C for a maximum period of 3 months prior to analysis. The complement factor 3 cleavage product C3c was determined in a central laboratory at the Hygiene Institute (before 1274 1990 using immunoprecipitation methods and after 1990 with nephelometry; all analy- ses with C3c data in this study were adjusted for the two different analytic methods using regression analysis (Fink et al. 1989; Stiller- Winkler et al. 1989). Follow‑up questionnaire and investiga ‑ tion. In 2006, study participants received a follow-up questionnaire [a modified version of the baseline questionnaire that included additional questions on diabetes (age of onset, treatment) and other diseases] in the mail from the local health departments where the baseline investigation already had taken place. The health authorities from Herne could not participate in 2006, so addresses from Herne were missing. The self-administered question- naire included the questions from the baseline questionnaire and, in addition, several items on cardiometabolic diseases. For example, we asked whether the participants had ever been diagnosed by a physician with hyper- lipidemia, myocardial infarction, stroke, or diabetes. With respect to diabetes, the year of diagnosis, antidiabetic treatment, and type of medication were asked. The incidence of physician-diagnosed diabetes after 1990 was chosen as the main outcome (16-year inci- dence). The beginning of antidiabetic treat- ment was not documented. The vast majority of incident diabetes cases in this age group can be assumed to have type 2 diabetes. In the case of Borken (control region), where some of the baseline examinations were performed in 1993 and 1994, we counted only diagnoses after these dates as cases. In the 2008–2009 clinical examination, the same questions on diabetes as in the 2006 questionnaire were asked in an interview. These data were used to test the reliability of the questionnaire results. Assessment of exposure to ambient air pollution. We used four methods with dif- ferent spatial scales to characterize exposure of the women [see Supplemental Material (doi:10.1289/ehp.0901689)]. First, data from monitoring stations maintained by the State Environment Agency covering the Ruhr area in an 8-km grid were used to reflect broad-scale spatial variation in air quality. The 5-year means of 1986–1990 at the meas- urement stations, which were located nearest to the home addresses of the women, were used. Second, we assessed the exposure to motor vehicle exhaust (1-km grid) by using emission inventories provided by the State Environment Agency. The agency estimated the annual mass of PM and NO2 emitted per square kilometer from road traffic. We used the emission inventory from 1994 to charac- terize emissions in the square kilometer where the women lived. Third, we applied land-use regression models to assign estimated NO2 and soot concentrations from traffic-related sources to the residential address of each individual (Brauer et al. 2003; Hochadel et al. 2006). Briefly, the models were based on a 1-year measurement program conducted in 2002. Concentrations of NO2, fine PM [aerodynamic diameter ≤ 2.5 µm (PM2.5)], and filter absorbance of PM2.5 were meas- ured at 40 points in two regions (Duisburg, Borken) based on 14-day samples for each season (spring, summer, fall, winter) and site. The models could explain 92% and 87% of the variance in NO2 and PM2.5 absor- bance, respectively. Modeled NO2 and PM2.5 absorbance (soot) were then applied to the women’s addresses in the year 1990. Fourth, exposure was characterized by the distance from home address at baseline investigation to the next major road with > 10,000 cars per day (highly exposed: distance to street < 100 m). During 1985–1995 a steep decline in air pollution, especially in PM pollu- tion, took place in Germany. However, this did not affect the spatial pattern of traffic- related pollution in our investigation area. The correlations were fairly stable over time [see Supplemental Material (doi:10.1289/ ehp.0901689)]. The ranking of traffic-related exposure remained the same throughout the follow-up period of 16 years. We therefore assumed that measurements performed after the end of the baseline investigation still reflected the pattern of pollution the women were exposed to before 1990 and are valid to determine the association between pollution pattern and the incidence of diabetes. Because of the steep decline of air pollution, we used air pollution data from 1990 and started counting incident cases of diabetes from 1990 to 2006 instead of using data from the indi- vidual time points of the baseline investiga- tion. Therefore, length of follow-up is most likely not confounded by exposure at baseline. Statistical analyses. Data are given as pro- portions for categorized variables or means and SD or geometric means and geometric SDs for continuous variables with normal or with log-normal distribution, respectively. Chi-square tests and F-tests were used to detect significant differences between groups. We analyzed the association of type 2 dia- betes incidence with ambient air pollution exposure using Cox regression analyses and accounted for ties using the exact method. Incident cases were women who reported being newly diagnosed with diabetes by a physician after 1990. Hazard ratios (HRs) with corresponding 95% confidence inter- vals (CIs) were estimated for increases of 1 interquartile range (IQR; calculated from the distribution of the whole sample) in PM or NO2 exposure and for residential address < 100 m to a busy road. The level of sig- nificance was set as 0.05. Age, body mass ovlume 118 | number 9 | September 2010 • Environmental Health Perspectives