title: Advanced glycation urinary protein-bound biomarkers and severity of diabetic nephropathy in man.
abstract: OBJECTIVE
  The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes.
  
  
  METHODS
  Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) <20 μg/min), microalbuminuria (Micro, AER 20-200 μg/min) or macroalbuminuria (Macro, AER ≥200 μg/min). Serum and urine AGE-modified proteins were measured.
  
  
  RESULTS
  In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes.
  
  
  CONCLUSIONS
  Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts.
authors.affiliation: Glycation and Diabetes Complications, Baker IDI Heart and Diabetes Institute, St Kilda Rd. Central, Melbourne, VIC 8008, Australia. melinda.coughlan@bakeridi.edu.au
authors.forename: Melinda T
authors.initials: MT
authors.lastname: Coughlan
authors.forename: Sheila K
authors.initials: SK
authors.lastname: Patel
authors.forename: George
authors.initials: G
authors.lastname: Jerums
authors.forename: Sally A
authors.initials: SA
authors.lastname: Penfold
authors.forename: Tuong-Vi
authors.initials: TV
authors.lastname: Nguyen
authors.forename: Karly C
authors.initials: KC
authors.lastname: Sourris
authors.forename: Sianna
authors.initials: S
authors.lastname: Panagiotopoulos
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Srivastava
authors.forename: Mark E
authors.initials: ME
authors.lastname: Cooper
authors.forename: Louise M
authors.initials: LM
authors.lastname: Burrell
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Macisaac
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000652:urine; D003928:Diabetic Nephropathies / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced