title: Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema.
abstract: OBJECTIVE
  Diabetic retinopathy is a frequent microvascular complication. In search of novel risk markers, we analysed the association between serum levels of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML) and prevalence of advanced stages of retinopathy in Type 2 diabetic patients without nephropathy.
  
  
  METHODS
  We carried out a case-control study of Type 2 diabetic patients with and without advanced stages of diabetic retinopathy. Retinopathy and macular oedema were defined according to standard criteria. Serum levels of CML were estimated by means of a novel competition-based ELISA assay.
  
  
  RESULTS
  Serum levels of CML were significantly different between age-matched controls (n=792; mean value +/- SD: 521+/-134 ng/ml), Type 2 diabetic patients without severe retinopathy (821+/-141 ng/ml; p<0.0001) and Type 2 diabetic patients with proliferative retinopathy (1182+/-346 ng/ml; p<0.0001). Levels of CML greater than 1000 ng/ml represented a 25-fold increase in risk of proliferative retinopathy. Receiver operating characteristics analysis revealed a CML threshold of 1087 ng/ml (100% sensitivity, 93% specificity) for clinically significant macular oedema.
  
  
  CONCLUSIONS
  High serum levels of CML were associated with advanced stages of retinopathy. Serum levels were shown to be a progressive risk marker, whereby a level of more than 1000 ng/ml induced a 25-fold increase in risk of proliferative retinopathy and clinically significant macular oedema. Our data suggest that serum levels of CML provide a novel risk marker for advanced stages of diabetic retinopathy in Type 2 diabetic patients.
authors.affiliation: Division of Endocrinology and Diabetes, Department of Internal Medicine, University of Ulm, Ulm, Germany. bernhard.boehm@medizin.uni-ulm.de
authors.forename: B O
authors.initials: BO
authors.lastname: Boehm
authors.forename: S
authors.initials: S
authors.lastname: Schilling
authors.forename: S
authors.initials: S
authors.lastname: Rosinger
authors.forename: G E
authors.initials: GE
authors.lastname: Lang
authors.forename: G K
authors.initials: GK
authors.lastname: Lang
authors.forename: R
authors.initials: R
authors.lastname: Kientsch-Engel
authors.forename: P
authors.initials: P
authors.lastname: Stahl
mesh_terms: D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000097:blood*; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood*; D008268:Macular Degeneration / Q000097:blood*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; C054688:N(6)-(1-carboxyethyl)lysine; D008239:Lysine