title: High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes.
abstract: BACKGROUND
  Modified low-density lipoprotein (LDL) immune complexes (IC) have proinflammatory properties and play a role in albuminuria development.
  
  
  METHODS
  We measured oxidized LDL (oxLDL) and advanced glycation end-product (AGE)-LDL in IC isolated from sera of Type 1 diabetic subjects followed for 14-20 years and studied their association with abnormal albuminuria. Patients with albumin excretion rates (AER)<40 mg/24 h at baseline and follow-up (n=302) were deemed resistant to developing abnormal albuminuria. Patients with AER<40 mg/24 h at baseline whose AER levels progressed to >40 mg/24 h were considered prone to abnormal albuminuria (n=185), those who progress to AER>299 mg/24 h were considered as having macroalbuminuria (n=57). The odds of developing abnormal albuminuria were estimated by logistic regression based on natural log-transformed levels of oxLDL and AGE-LDL in IC and stratified by baseline AER decile.
  
  
  RESULTS
  OxLDL and AGE-LDL were significantly higher in IC isolated from patients progressing to abnormal albuminuria. In unadjusted conditional logistic analysis, an increase of 1 SD in oxLDL and AGE-LDL levels in IC significantly increased the odds ratio (OR) for development of macroalbuminuria, respectively, by a factor of 2.5 and 1.8 (P<0.001, P=0.008). The increased odds of developing macroalbuminuria remained significant when adjusted for treatment group, diabetes duration, retinopathy, baseline hemoglobin A1c and LDL (OR=2.5 and 1.8, respectively, P<0.01).
  
  
  CONCLUSIONS
  Higher levels of oxLDL and AGE-LDL in circulating IC were associated with increased odds to develop abnormal albuminuria.
authors.affiliation: Department of Medicine and Laboratory Services, Medical University of South Carolina and Ralph H. Johnson VA Medical Center, Charleston, SC, USA. virellam@musc.edu
authors.forename: Maria F
authors.initials: MF
authors.lastname: Lopes-Virella
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Baker
authors.forename: John
authors.initials: J
authors.lastname: Lachin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Virella
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D048909:Diabetes Complications / Q000097:blood / Q000209:etiology* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology* / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000276:immunology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000936:Antigen-Antibody Complex; D017127:Glycation End Products, Advanced; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde