title: Is diabetes an acquired disorder of reactive glucose metabolites and their intermediates?
abstract: OBJECTIVE
  We hypothesised that diabetic patients would differ from those without diabetes in regard to the handling of glucose-derived reactive metabolites, evidenced by triosephosphate intermediates (TP(INT)) and methylglyoxal (MG), irrespective of the type of diabetes, plasma glucose level or HbA(1c) value.
  
  
  METHODS
  To test this hypothesis, erythrocytes were isolated from patients with type 1 (n = 12) and type 2 (n = 12) diabetes with varying blood glucose and HbA(1c) levels. These were then compared with erythrocytes isolated from individuals without diabetes (n = 10), with respect to MG, as determined by HPLC, and TP(INT), as determined by endpoint enzymatic assays.
  
  
  RESULTS
  The concentrations of intracellular TP(INT) and MG were significantly elevated in erythrocytes from diabetic patients. Normalisation of either TP(INT) or MG to intracellular glucose concentration (nmol glucose/mgHb) confirmed that erythrocytes from diabetic patients accumulated more reactive metabolites than did those from healthy controls.
  
  
  CONCLUSIONS
  Diabetic patients can be characterised by an increased formation of TP(INT) and MG. The 25-fold increase of MG in type 1 and the 15-fold increase in type 2 diabetes, together with a several-fold increase in TP(INT) and decreased glyceraldehyde-3-phosphate dehydrogenase activity even under normal glucose conditions, imply that normalising glucose level cannot completely prevent late diabetic complications until this acquired error of metabolism has been restored.
authors.affiliation: Department of Medicine and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Fleming
authors.forename: J
authors.initials: J
authors.lastname: Cuny
authors.forename: G
authors.initials: G
authors.lastname: Nawroth
authors.forename: Z
authors.initials: Z
authors.lastname: Djuric
authors.forename: P M
authors.initials: PM
authors.lastname: Humpert
authors.forename: M
authors.initials: M
authors.lastname: Zeier
authors.forename: A
authors.initials: A
authors.lastname: Bierhaus
authors.forename: P P
authors.initials: PP
authors.lastname: Nawroth
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011765:Pyruvaldehyde / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011765:Pyruvaldehyde