Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Diabetes Care. 2008 Oct;31(10):2006-12. doi: 10.2337/dc08-0659. Epub 2008 Jul 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Albuminuria / epidemiology
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Carotid Arteries / pathology
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetic Angiopathies / epidemiology*
  • Diabetic Angiopathies / prevention & control
  • Diabetic Nephropathies / epidemiology*
  • Diabetic Nephropathies / prevention & control
  • Endothelium, Vascular / pathology*
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / epidemiology*
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Models, Statistical
  • Regression Analysis
  • Risk Factors
  • Tunica Intima / pathology
  • Tunica Media / pathology


  • Biomarkers
  • C-Reactive Protein