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Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.

TitleCirculating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study.
Publication TypeJournal Article
Year of Publication2007
AuthorsHoogeveen RC, Ballantyne CM, Bang H, Heiss G, Duncan BB, Folsom AR, Pankow JS
JournalDiabetologia
Volume50
Issue1
Pagination36-42
Date Published2007 Jan
ISSN0012-186X
KeywordsAfrican Americans, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Humans, Incidence, Inflammation, Intercellular Adhesion Molecule-1, Lipoproteins, LDL, Male, Middle Aged, Oxidative Stress, Proportional Hazards Models, Prospective Studies, Risk Factors
Abstract

AIMS/HYPOTHESIS: 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.

MATERIALS AND 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/INTERPRETATION: 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.

DOI10.1007/s00125-006-0533-8
Alternate JournalDiabetologia
PubMed ID17136392
Grant ListN01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
R01-DK56918 / DK / NIDDK NIH HHS / United States