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Published online July 15, 2008
Diabetes Care 31:2006-2012, 2008
DOI: 10.2337/dc08-0659
© 2008 by the American Diabetes Association
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Pathophysiology/Complications
Original Research

Risk Factors Related to Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort and Their Relationship With Nephropathy and Macrovascular Complications

Maria F. Lopes-Virella, MD, PHD1, Rickey E. Carter, PHD2, Gregory E. Gilbert, MS2, Richard L. Klein, PHD1, Miran Jaffa, PHD2, Alicia J. Jenkins, MD1,3, Timothy J. Lyons, MD1,3, W. Timothy Garvey, MD1,4, Gabriel Virella, MD, PHD5 and the DCCT/EDIC Cohort Study Group

1 Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, South Carolina
2 Department of Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, Charleston, South Carolina
3 Section of Endocrinology, Oklahoma University of Health Sciences Center, Oklahoma City, Oklahoma
4 Department of Nutrition, University of Alabama, Birmingham, Alabama
5 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina

Corresponding author: Maria F. Lopes-Virella, virellam{at}musc.edu

OBJECTIVE—Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

RESEARCH DESIGN AND METHODS—We determined which of these risk factors or clusters thereof are associated with the presence of and subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]).

RESULTS—After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol, and smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P < 0.01) and soluble E-selectin had a strong association with nephropathy (P < 0.01).

CONCLUSIONS—The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.


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