title: Baseline markers of inflammation are associated with progression to macroalbuminuria in type 1 diabetic subjects.
abstract: OBJECTIVE
  The current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria.
  
  
  METHODS
  Levels of inflammation and endothelial cell dysfunction biomarkers were measured in 1,237 of 1,441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline. To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, micro-, and macroalbuminuria were the outcomes of interest.
  
  
  RESULTS
  In the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and -2 lead to a 30-50% increase in the odds to develop macroalbuminuria. Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and -2 but not for IL-6 or PAI-1.
  
  
  CONCLUSIONS
  Our study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and -2, are important predictors of macroalbuminuria in patients with type 1 diabetes.
authors.affiliation: Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H Johnson VA Medical Center, Charleston, South Carolina, USA. virellam@musc.edu
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Baker
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Hunt
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cleary
authors.forename: Richard
authors.initials: R
authors.lastname: Klein
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000209:etiology*; D015415:Biomarkers / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II