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

  1. Maria F. Lopes-Virella, MD, PHD1,
  2. Rickey E. Carter, PHD2,
  3. Gregory E. Gilbert, MS2,
  4. Richard L. Klein, PHD1,
  5. Miran Jaffa, PHD2,
  6. Alicia J. Jenkins, MD13,
  7. Timothy J. Lyons, MD13,
  8. W. Timothy Garvey, MD14,
  9. Gabriel Virella, MD, PHD5 and
  10. and the DCCT/EDIC Cohort Study Group
  1. 1Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, South Carolina
  2. 2Department of Biostatistics, Bioinformatics, and Epidemiology, Medical University of South Carolina, Charleston, South Carolina
  3. 3Section of Endocrinology, Oklahoma University of Health Sciences Center, Oklahoma City, Oklahoma
  4. 4Department of Nutrition, University of Alabama, Birmingham, Alabama
  5. 5Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
  1. Corresponding author: Maria F. Lopes-Virella, virellam{at}musc.edu

Abstract

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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 15 July 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted July 10, 2008.
    • Received April 3, 2008.
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  1. doi: 10.2337/dc08-0659 Diabetes Care October 2008 vol. 31 no. 10 2006-2012
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