Key result
Composite scores of acute-phase reactants (OR 2.78; 95% CI 1.42-5.42), thrombolytic factors, and cytokines/adipokines were associated with higher levels of atherosclerosis at EDIC year 12.
Why the study?
Are composite scores of inflammatory, thrombotic, and endothelial biomarkers associated with subclinical atherosclerosis in patients with type 1 diabetes?
Cohort (n=886)
Are composite scores of inflammatory, thrombotic, and endothelial biomarkers associated with subclinical atherosclerosis in patients with type 1 diabetes?
Odds Ratio: 2.78 (95% CI 1.42–5.42)
Composite scores of inflammatory and thrombotic biomarkers are associated with subclinical atherosclerosis in type 1 diabetes, though individual biomarkers are not predictive.
Supports inflammatory pathways in type 1 diabetes atherosclerosis; hypothesis-generating and should not yet alter clinical practice.
OBJECTIVE: There is considerable interest in identifying biomarkers that predict high risk for the development of macrovascular complications in patients with diabetes. Therefore, the longitudinal association between subclinical atherosclerosis as measured by internal carotid artery intima-media thickness (IMT) and acute-phase reactants, cytokines/adipokines, thrombosis, and adhesion molecules was examined. RESEARCH DESIGN AND METHODS: Biomarkers were measured at four time points over 20 years in 886 DCCT/EDIC participants with type 1 diabetes. Four composite scores were created by combining z scores generated from within the data set of individual biomarkers: acute-phase reactants (fibrinogen, C-reactive protein), thrombosis (fibrinogen, active and total plasminogen activator inhibitor [PAI]-1), cytokines/adipokines (tumor necrosis factor receptor-1 and -2, active and total PAI-1, IL-6), and endothelial dysfunction (soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble E-selectin). Internal carotid IMT was measured at EDIC years 1, 6, and 12, with elevated IMT defined at each time point as being in the upper quintile of its distribution. RESULTS: Logistic regression models indicate that while individual biomarkers were not predictive of or associated with subclinical atherosclerosis, composite scores of acute-phase reactants (odds ratio [OR] 2.78 [95% CI 1.42, 5.42]), thrombolytic factors (OR 2.83 [95% CI 1.45, 5.52]), and cytokines/adipokines (OR 2.83 [95% CI 1.48, 5.41]) measured at our final time point EDIC years 8-11 were associated with higher levels of atherosclerosis at EDIC year 12, but findings were not consistent at early time points. The endothelial dysfunction score was not appreciably predictive of or associated with subclinical atherosclerosis at any of the time points measured. CONCLUSIONS: The pathophysiologic relationship between higher biomarker levels and progression of subclinical atherosclerosis remains unclear.
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Hunt et al. (2015) conducted a cohort in Type 1 diabetes (n=886). Elevated composite scores of acute-phase reactants, thrombolytic factors, and cytokines/adipokines was evaluated on Elevated internal carotid IMT (upper quintile) at EDIC year 12 (OR 2.78, 95% CI 1.42-5.42). Composite scores of acute-phase reactants (OR 2.78; 95% CI 1.42-5.42), thrombolytic factors, and cytokines/adipokines were associated with higher levels of atherosclerosis at EDIC year 12.
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