1. Diabetes incidence and long-term exposure to air pollution: a cohort study Zorana Jovanovic Andersen 14.09.2011 ISEE

2. Diabetes  Diabetes epidemic, cased in large part by obesity epidemic and physical inactivity  Metabolic disease, high blood sugar, type-2, insulin resistance  In USA

3. Background: Diabetes & Air Pollution  Diabetes established modifier of a link between air pollution and CVD (inflammation, endothelial dysfunction, prothrombotic changes, altered heart rate variability)  Biological mechanism prolonged exposure to air pollution involves inflammation in adipose tissue, increased blood glucose levels, insulin resistance, glucose intolerance in mice  Short-term exposure to elevated air pollution linked to increased risk of diabetes mortality and hospitalization

4. Evidence: Diabetes Prevalence & Air Pollution

5. Evidence: Diabetes Incidence & Air Pollution

6. Aim of this study  We studied the association between traffic-related air pollution levels at the residence and the risk for diabetes in an elderly Danish cohort, and tested for an effect modification by lifestyle, education, and co-morbid conditions.

7. Methods - Cohort  Danish Diet, Cancer and Health cohort  57 053 subjects, Copenhagen and Aarhus  Interviewed in 1993-1997 (baseline)  Age 50-65 years  Linkage to Central Population Registry and Danish Address Database - residential address history (1971)  Linkage to Danish National Diabetes Register (1995) for assessment of health outcome

8. Danish Diabetes Register  The NDR was established by linking existing nationwide administrative records in the Danish healthcare system Source of DataInclusion Criteria National Patient Register (NPR) hospitals discharge diagnoses (1994) hospital admission for diabetes: ICD10: DE10-14, DH36.0, DO24, or ICD8: 249, 250 National Health Insurance Registry (NHISR) with information of all services provided by general and specialist practitioners (1973) 1. chiropody for diabetic patients; 2. five blood glucose measurements within 1 year 3. two blood glucose measurements per year for five consecutive years registered Register of Medicinal Product Statistics (RMPS) containing all prescriptions dispensed at Danish pharmacies (1993) second purchase of insulin or oral glucose-lowering drugs within 6 months

9. Danish Diabetes Register  Results of blood glucose measurements are not included  50-60% of the patients > 1 inclusion criterion  Not possible to distinguish type 1 and type 2 diabetes  Due to different dates of initiation of the underlying registers and accumulation of prevalent cases, only incidence values after 1 January 1995 were found to be reliable  Incidence of diabetes was defined as the earliest record in the diabetes register occurring after 1 January 1995, between baseline (1993-1997) and 27 June 2006.

10. Methods – Air Pollution Exposure  AirGIS dispersion model, sum of: 1) regional background, 2) urban background, & 3) street level contribution  Input for AirGIS model  Street/building geometry  Street network and traffic data  Meteorology GIS Maps building height, street width, open sector Traffic counts, emission factors, density, speed, types, variation patterns over time

11. Methods – Air Pollution Exposure  AirGIS Model output:  Annual mean NO 2 /NO x concentrations at individual address Flow and dispersion inside a street canyon

12. Methods – Statistical Model  Cox proportional hazards model, left truncation at age at baseline, and right censoring at age at hospital admission for ACS, death, emigration, or 27 June 2006  NO 2 /NO x, time-dependent variables, the estimates per IQR  Confounders: smoking (status, intensity, duration, ETS), occupational exposures, BMI, educational level, fruit consumption  Effect modification: interaction term, Wald-test  Spline (rcs) in R, for dose-repsonse curve

13. Results 570535181840402877 Exclusions: -571 cancer before baseline -962 missing address or geocode -1 341 missing address -1 147 self-reported diabetes at baseline -173 diabetes record in the NDR before baseline -6 with diabetes between baseline and 01.01.1995 -1 035 missing covariates 7.8% diabetes originally included in NDR Incidence rate: 8 per1 000 person-years 5.5% diabetes ‘strict definition’ Incidence rate: 5.7 per 1 000 person-years ”Confirmed Diabetes” Original Cohort Final Study Population ”All Diabetes” Exclusion of 1163 included solely due to blood glucose measurements

14. Results

15. Results: Exposure to Air Pollution

16. Results: Main Analysis Model WITHOUT waist-to-hip ratio: 1.05 (1.02-1.10) Model WITHOUT BMI and waist-to- hip ratio: 1.08 (1.04-1.12)

17. Results: Effect Modification

19. Results: dose-response

20. Conclusions  The risk for diabetes was weakly positively associated with increasing mean levels of traffic-related air pollution at the residence  The risk was highest in non-smokers and physically active people, those with a-priori low risk