Diabetes incidence and long-term exposure to air pollution: a cohort study

Zorana Jovanovic Andersen 14.09.2011 ISEE

Diabetes Diabetes epidemic, cased in large part by

obesity epidemic and physical inactivity Metabolic disease, high blood sugar, type-2,

insulin resistance In USA

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

Evidence: Diabetes Prevalence & Air Pollution

Evidence: Diabetes Incidence & Air Pollution

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.

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

Danish Diabetes Register The NDR was established by linking existing

nationwide administrative records in the Danish healthcare systemSource of Data Inclusion 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 year3. 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

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.

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

Road centre lineAddress point

BuildingRoad centre lineAddress point

Building

GIS Maps building height, street width, open sector

Traffic counts, emission factors, density, speed, types, variation patterns over time

Methods – Air Pollution Exposure AirGIS Model output:

Annual mean NO2 /NOx concentrations at individual address

NOX (Class)

680000 690000 700000 710000 720000 730000

6140000

6150000

6160000

6170000

6180000

6190000

6200000

6210000

6220000

1 2 3 4 5 6 7 8 9 10

a)

Lille Valby

wind

Leeward Windward

Recirculated pollution

Direct emission

Background pollution

Flow and dispersion inside a street canyon

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

NO2 /NOx ,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

Results5705

35181

84040

2877

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

Results

Results: Exposure to Air Pollution0

510

1520

Per

cent

10 20 30 40 50 60NO2 (µg/m3)

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)

Results: Effect Modification

Results: Effect Modification

Results: dose-response

NO2 (µg/m3)

log

Rel

ativ

e H

azar

d

10 20 30 40 50 60

-0.2

0.0

0.2

0.4

0.6

0.8

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