title: The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes.
abstract: OBJECTIVE
  This study was undertaken to determine whether levels of inflammation and endothelial dysfunction biomarkers in serum samples collected at baseline in the Diabetes Control and Complications Trial (DCCT) cohort could predict the development of retinopathy.
  
  
  METHODS
  Levels of clotting/fibrinolysis, inflammation and endothelial dysfunction biomarkers were measured in 1391 subjects with type 1 diabetes to determine whether their levels predicted increased risk to develop or accelerate progression of retinopathy during 16years of follow-up.
  
  
  RESULTS
  Using regression models adjusted for DCCT treatment group, duration of diabetes, baseline retinopathy scores, HbA1c and albumin excretion rate, the baseline levels of sE-selectin and PAI-1 (active) were significantly associated with increased risk of a 3-step progression in retinopathy score in the primary prevention cohort (PPC). After adjusting for additional covariates (e.g., ACE/ARB and statin therapy), this association persisted. Levels of active and total PAI-1 in the same group were also significantly associated, after similar adjustments, with the time to progress to severe non-proliferative retinopathy during the follow-up period (54 and 29%, respectively of increased risk). No associations were observed in the secondary intervention cohort for any of the outcomes.
  
  
  CONCLUSIONS
  High levels of sE-selectin and PAI-1 are associated with the development of retinopathy in patients with uncomplicated type 1 diabetes.
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Hussein A
authors.initials: HA
authors.lastname: Rajab
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Baker
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Hunt
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Klein
authors.affiliation: The Biostatistics Center, George Washington University, Washington DC, Washington DC, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cleary
authors.affiliation: The Biostatistics Center, George Washington University, Washington DC, Washington DC, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lachin
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Medical Genetics, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson VA Medical Center, Charleston, SC, USA. Electronic address: virellam@musc.edu.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D003930:Diabetic Retinopathy / Q000097:blood* / Q000503:physiopathology; D018450:Disease Progression; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D031300:Retinal Vasculitis / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D012189:Retrospective Studies; D018570:Risk Assessment; D012380:Role; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; D018836:Inflammation Mediators; D017395:Plasminogen Activator Inhibitor 1; D002097:C-Reactive Protein
keywords: Biomarkers; Diabetes complications; E-selectin; Plasminogen activator inhibitor type 1; Retinopathy; Type 1 diabetes