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Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate

¹Steno Diabetes Center, Gentofte, Denmark
²Department of Internal Medicine, Academic Hospital Maastricht, The Netherlands
³Faculty of Health Science, Aarhus University, Aarhus, Denmark
⁴Department of Medical Endocrinology, Rigshospitalet, Copenhagen, Denmark

ansa{at}steno.dk

ABSTRACT

Objectives: We evaluated the association of biomarkers of endothelial dysfunction and inflammation with all-cause mortality and cardiovascular mortality and morbidity, and decline in glomerular filtration rate (GFR) in type 1 diabetic patients.

Material and Methods: We prospectively followed 199 type 1 diabetic patients with diabetic nephropathy and 192 patients with persistent normoalbuminuria. Biomarkers were measured at baseline.

Results: We constructed 2 Z-scores: the mean inflammatory Z-score combined C-reactive protein, interleukin-6, soluble intercellular adhesion molecule (sICAM-1), and secreted phospholipase A(2) and the mean Z-score for endothelial dysfunction combined soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1, and sICAM-1.

The mean Z-score of inflammatory biomarkers was associated with mortality and the combined endpoint in patients with diabetic nephropathy after multivariate adjustment (Hazard Ratio (HR) 1.7, 95% Confidence Interval, 1.1-2.6; p=0.025, and 1.5 (1.1-2.2); p=0.017).

The mean Z-score for endothelial dysfunction biomarkers was associated with mortality in a model adjusting for age and gender in patients with diabetic nephropathy (HR 1.6 (1.0-2.3); p=0.031).

The mean Z-score for endothelial dysfunction correlated with decline in GFR (r= –0.243; p=0.001); the correlation persisted after multivariate adjustment: Coefficient: –1.38 (95% CI –2.27, –0.50), p=0.002.

Conclusions: Mean Z-score of inflammatory biomarkers are significantly associated with all-cause mortality and cardiovascular morbidity and mortality in patients with nephropathy after multivariate adjustment. These data suggest that the high risk of cardiovascular disease in type 1 diabetes maybe explained in part by inflammatory activity. Mean Z-score of endothelial dysfunction correlated after multivariate adjustment with the rate of decline in GFR.

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