Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.
OBJECTIVE
To evaluate the role of oxidative stress and inflammation in the aetiology of type 2 diabetes, we examined the association of oxidised LDL (ox-LDL) and soluble intercellular adhesion molecule-1 (sICAM-1) levels with type 2 diabetes incidence over 9 years in the Atherosclerosis Risk in Communities Study.


METHODS
In a large, prospective, case-cohort design, ox-LDL and sICAM-1 were measured in stored plasma samples collected at baseline in stratified samples of 581 diabetes cases and 572 non-cases selected from 10,275 middle-aged men and women without prevalent diabetes at baseline.


RESULTS
Compared with non-cases, diabetes cases had significantly higher mean baseline levels of ox-LDL and sICAM-1. Elevated ox-LDL and sICAM-1 were both associated with increased risk of incident diabetes after adjustment for age, sex, race and centre, with hazard ratios for the highest vs lowest tertiles of 1.68 (95% CI 1.25-2.24) and 1.91 (95% CI 1.45-2.50), respectively. After additional adjustment for fasting glucose, waist circumference, HDL-cholesterol, triacylglycerol, hypertension and C-reactive protein, only sICAM-1 remained an independent predictor of incident diabetes (hazard ratio 1.50; 95% CI 1.02-2.23).


CONCLUSIONS
In this community-based cohort of middle-aged US adults, elevated plasma ox-LDL and sICAM-1 levels were associated with increased risk of type 2 diabetes. Measurement of ICAM-1 or ox-LDL, or other measures related to inflammation or oxidative stress, may be helpful in identifying those patient populations in which to test whether novel therapies that inhibit specific pathways related to inflammation or oxidative stress are beneficial in the prevention of diabetes in humans.
Hoogeveen
R C
RC
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX, USA. ronh@bcm.tmc.edu
Ballantyne
C M
CM
Bang
H
H
Heiss
G
G
Duncan
B B
BB
Folsom
A R
AR
Pankow
J S
JS
D001741:Black or African American; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D044465:White People
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1