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  • Title: Diabetic retinopathy risk correlates with intracellular concentrations of the glycoxidation product Nepsilon-(carboxymethyl) lysine independently of glycohaemoglobin concentrations.
    Author: Hammes HP, Brownlee M, Lin J, Schleicher E, Bretzel RG.
    Journal: Diabetologia; 1999 May; 42(5):603-7. PubMed ID: 10333054.
    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 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.
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