title: Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes.
abstract: OBJECTIVE
  Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease.
  
  
  METHODS
  We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intima-medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12.
  
  
  RESULTS
  OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r = 0.66-0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT ≥ 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81).
  
  
  CONCLUSIONS
  Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intima-medial thickening in patients with type 1 diabetes.
authors.affiliation: Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, United States; Ralph H. Johnson VA Medical Center, Charleston, SC, United States. Electronic address: huntke@musc.edu.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Hunt
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Baker
authors.forename: Patricia
authors.initials: P
authors.lastname: Cleary
authors.forename: Jye-Yu
authors.initials: JY
authors.lastname: Backlund
authors.forename: Timothy
authors.initials: T
authors.lastname: Lyons
authors.forename: Alicia
authors.initials: A
authors.lastname: Jenkins
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000150:complications / Q000276:immunology / Q000473:pathology*; D001794:Blood Pressure; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D016017:Odds Ratio; D015995:Prevalence; D012044:Regression Analysis; D055815:Young Adult
chemical_list: D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
keywords: Carotid artery intima–media thickness; Modified LDL; Subclinical atherosclerosis; Type 1 diabetes