Risk Factors related to Inflammation and Endothelial Dysfunction in the DCCT/EDIC Cohort and their Relationship with Nephropathy and Macrovascular Complications

doi:10.2337/dc08-0659

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, PhD (virellam{at}musc.edu)¹,
Rickey E. Carter, PhD²,
Gregory E. Gilbert, PhD²,
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 Study Group

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

Abstract

Objective: Since 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 (CRP and fibrinogen, soluble VCAM-1, ICAM-1 and E selectin, and fibrinolytic markers) in a sub-group of patients from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/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).

Results: After adjusting for conventional risk factors (age, gender, DCCT treatment group, diabetes duration, HbA1c, 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 sE-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 sE-selectin discriminate better patients with albuminuria than conventional risk factors.