Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Nepsilon-(carboxymethyl) lysine independently of glycohaemoglobin concentrations

Diabetologia. 1999 May;42(5):603-7. doi: 10.1007/s001250051201.


Aims/hypothesis: We investigated whether either the amount of diabetes-induced intracellular oxidative stress or the concentration of hyperglycaemia-induced advanced glycation endproducts is associated with the risk of diabetic retinopathy.

Methods: We measured concentrations of the glycoxidation product Nepsilon-(carboxymethyl)lysine and two non-oxidation-dependent advanced glycation end-products (methylglyoxal-derived and 3-deoxyglucosone-derived) in CD45RA+ T-cells from 21 Type I (insulin-dependent) diabetic patients with and without diabetic retinopathy and from age-matched nondiabetic control subjects.

Results: Intracellular concentrations of both oxidation-dependent Nepsilon-(carboxymethyl)lysine and oxidation-independent advanced glycation endproducts were increased in memory T-cells from diabetic patients. Nepsilon-(carboxymethyl)lysine: diabetic median-24176 arbitrary units/mg protein (95% confidence interval 18690-34099 arbitrary units/mg protein); nondiabetic-9088 arbitrary units/mg protein (confidence interval 6994-10696 arbitrary units/mg protein; p < 0.0001). Methylglyoxal-derived advanced glycation end products: diabetic-5430 arbitrary units/ mg protein (confidence interval 3458-13610); nondiabetic-271 arbitrary units/mg protein (confidence interval 61-760 arbitrary units/mg protein; p< 0.0001). 3-Deoxyglucosone-derived advanced glycation end products: diabetic-8070 arbitrary units/mg protein (confidence interval 7049-16551 arbitrary units/mg protein); nondiabetic-1479 arbitrary units/ mg protein (confidence interval 1169-3170; p< 0.0001). Only Nepsilon-(carboxymethyl)lysine concentrations, however, inversely correlated with the duration of retinopathy-free diabetes (r = -0.51; p < 0.02). Diabetes-dependent Nepsilon-(carboxymethyl)lysine accumulation did not correlate with age, diabetes duration, or averaged glycohaemoglobin concentrations. In vitro experiments wih menadione and lymphocytes confirmed that Nepsilon-(carboxymethyl)lysine concentrations reflect intracellular oxidative stress.

Conclusion/interpretation: Monitoring intracellular concentrations of increased oxidative stress in long-lived CD45RA+ lymphocytes by markers such as Nepsilon-(carboxymethyl)lysine possibly identifies a subgroup of patients at high risk for microvascular complications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Deoxyglucose / analogs & derivatives
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetic Retinopathy / blood*
  • Female
  • Glycated Hemoglobin A / analysis*
  • Glycation End Products, Advanced / blood
  • Humans
  • Leukocyte Common Antigens / analysis
  • Lysine / analogs & derivatives*
  • Lysine / blood
  • Male
  • Middle Aged
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Pyruvaldehyde
  • Risk Factors
  • T-Lymphocytes / chemistry*
  • T-Lymphocytes / immunology


  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • 3-deoxyglucose
  • N(6)-carboxymethyllysine
  • Pyruvaldehyde
  • Deoxyglucose
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Lysine