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  • Title: Elevated serum levels of N(epsilon)-carboxymethyl-lysine, an advanced glycation end product, are associated with proliferative diabetic retinopathy and macular oedema.
    Author: Boehm BO, Schilling S, Rosinger S, Lang GE, Lang GK, Kientsch-Engel R, Stahl P.
    Journal: Diabetologia; 2004 Aug; 47(8):1376-9. PubMed ID: 15258735.
    Abstract:
    AIMS/HYPOTHESIS: Diabetic retinopathy is a frequent microvascular complication. In search of novel risk markers, we analysed the association between serum levels of the major advanced glycation end product N(epsilon)-carboxymethyl-lysine (CML) and prevalence of advanced stages of retinopathy in Type 2 diabetic patients without nephropathy. METHODS: We carried out a case-control study of Type 2 diabetic patients with and without advanced stages of diabetic retinopathy. Retinopathy and macular oedema were defined according to standard criteria. Serum levels of CML were estimated by means of a novel competition-based ELISA assay. RESULTS: Serum levels of CML were significantly different between age-matched controls (n=792; mean value +/- SD: 521+/-134 ng/ml), Type 2 diabetic patients without severe retinopathy (821+/-141 ng/ml; p<0.0001) and Type 2 diabetic patients with proliferative retinopathy (1182+/-346 ng/ml; p<0.0001). Levels of CML greater than 1000 ng/ml represented a 25-fold increase in risk of proliferative retinopathy. Receiver operating characteristics analysis revealed a CML threshold of 1087 ng/ml (100% sensitivity, 93% specificity) for clinically significant macular oedema. CONCLUSIONS/INTERPRETATION: High serum levels of CML were associated with advanced stages of retinopathy. Serum levels were shown to be a progressive risk marker, whereby a level of more than 1000 ng/ml induced a 25-fold increase in risk of proliferative retinopathy and clinically significant macular oedema. Our data suggest that serum levels of CML provide a novel risk marker for advanced stages of diabetic retinopathy in Type 2 diabetic patients.
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