Diabetologia

, Volume 42, Issue 5, pp 603–607

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

  • H.-P. Hammes
  • M. Brownlee
  • J. Lin
  • E. Schleicher
  • R. G. Bretzel
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DOI: 10.1007/s001250051201

Cite this article as:
Hammes, HP., Brownlee, M., Lin, J. et al. Diabetologia (1999) 42: 603. doi:10.1007/s001250051201

Abstract

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 Ne-(carboxymethyl)lysine and two non-oxidation-dependent advanced glycation endproducts (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 non-diabetic control subjects. Results. Intracellular concentrations of both oxidation-dependent Ne-(carboxymethyl)lysine and oxidation-independent advanced glycation endproducts were increased in memory T-cells from diabetic patients. Ne-(carboxymethyl)lysine: diabetic median-24 176 arbitrary units/mg protein (95 % confidence interval 18 690–34 099 arbitrary units/mg protein); nondiabetic-9088 arbitrary units/mg protein (confidence interval 6994–10 696 arbitrary units/mg protein; p < 0.0001). Methylglyoxal-derived advanced glycation end products: diabetic-5430 arbitrary units/mg protein (confidence interval 3458–13 610); 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 7049–16 551 arbitrary units/mg protein); nondiabetic-1479 arbitrary units/mg protein (confidence interval 1169–3170; p < 0.0001). Only Ne-(carboxymethyl)lysine concentrations, however, inversely correlated with the duration of retinopathy-free diabetes (r = –0.51; p < 0.02). Diabetes-dependent Ne-(carboxymethyl)lysine accumulation did not correlate with age, diabetes duration, or averaged glycohaemoglobin concentrations. In vitro experiments wih menadione and lymphocytes confirmed that Ne-(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 Ne-(carboxymethyl)lysine possibly identifies a subgroup of patients at high risk for microvascular complications. [Diabetologia (1999) 42: 603–607]

Keywords Diabetic retinopathypredictionlymphocytesglycation.
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Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • H.-P. Hammes
    • 1
  • M. Brownlee
    • 2
  • J. Lin
    • 1
  • E. Schleicher
    • 3
  • R. G. Bretzel
    • 1
  1. 1.3 rd Medical Department, Centre of Internal Medicine, Justus-Liebig-University, Giessen, GermanyDE
  2. 2.Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USAUS
  3. 3.4 rd Medical Department, Eberhard-Karl-University, Tübingen, GermanyDE