Elevated Haemoglobin Levels of N––Carboxymethyllysine and Acrolein Lysine Adducts Are Associated With Proliferative Diabetic Retinopathy

Abstract

Purpose: : To investigate whether serum and haemoglobin levels of the advanced glycation/lipoxidation end product (AGE/ALE), N–ε–carboxymethyllysine (CML), and the ALE, acrolein lysine, are associated with the grade of retinopathy in diabetic patients.

Methods: : Serum and haemoglobin levels of CML and acrolein lysine were measured using a newly developed competitive ELISA in Type 1 and Type 2 diabetic patients (n=176; aged 60.15±1.27 years) with no retinopathy, non proliferative retinopathy or proliferative retinopathy, and in a non–diabetic control group (n=51; aged 52.49±2.52 years). Patients with macroalbuminuria were excluded from the study.

Results: : Levels of CML and acrolein lysine in serum were significantly increased in diabetic patients compared to healthy subjects (mean respective values were 138±3 and 121±7 µg/ml, p<0.01 for CML and 22±0.5 and 19±0.9 µg/ml, p<0.05 for acrolein). However, serum levels of these adducts failed to associate with the severity of retinopathy (p>0.05; one–way ANOVA). Haemoglobin levels of CML and acrolein lysine were also elevated in diabetic patients (mean respective values for diabetic and control subjects were 13.3±0.4 and 10.72±0.4 AU/mg, p<0.01 for CML and 0.36±0.02 and 0.23±0.04 AU/mg, p<0.01 for acrolein). While no differences in haemoglobin CML and acrolein lysine levels were apparent between control individuals and diabetic patients without retinopathy or with non proliferative retinopathy, these adducts were increased in patients with proliferative retinopathy (CML: 14.2±1.5 AU/mg p<0.05 vs control subjects; acrolein lysine: 0.42±0.03 AU/mg, p<0.01 vs controls).

Conclusions: : Our data suggest haemoglobin levels of CML and acrolein lysine may provide a useful risk marker for progression to proliferative diabetic retinopathy and that elevated intracellular ALE/AGE formation may be involved in the pathogenesis of the advanced stages of the disease.

Keywords: diabetes • diabetic retinopathy • retina