Evaluation of N(epsilon)-(3-formyl-3,4-dehydropiperidino)lysine as a novel biomarker for the severity of diabetic retinopathy

Aims/hypothesis Recent studies suggest that oxidative stress should be monitored alongside HbA(1c) to identify subgroups of diabetic patients at high risk of initiation or progression of retinopathy. The acrolein-derived advanced lipoxidation end-product (ALE), N(epsilon)-(3-formyl-3,4-dehydropiperidino) lysine (FDP-lysine), is a useful biomarker that reflects the cumulative burden of oxidative stress over long periods of time. The purpose of the present study was to investigate whether serum and haemoglobin levels of FDP-lysine are associated with the severity of diabetic retinopathy in type 1 and type 2 diabetic patients. Methods Serum and haemoglobin levels of FDP-lysine were measured by competitive ELISA in 59 type 1 and 76 type 2 diabetic patients with no retinopathy, non-proliferative retinopathy or proliferative retinopathy (mean age [+/- SEM] 54.3 +/- 1.3 years), and in 47 non-diabetic control individuals (mean age 51.9 +/- 2.1 years). Results Serum and haemoglobin levels of FDP-lysine were significantly increased in diabetic patients compared with control individuals (p=0.04 and p=0.002, respectively). However, no significant association was found between levels of serum FDP-lysine and the severity of diabetic retinopathy (p=0.97). In contrast, increased haemoglobin FDP-lysine levels were observed in patients with proliferative retinopathy compared with patients without retinopathy and with non-proliferative retinopathy (p=0.04). The relationship of FDP-lysine with proliferative retinopathy was unaltered after adjustment for HbA(1c), or other clinical parameters. Conclusions/interpretation Our data suggest that haemoglobin FDP-lysine may provide a useful risk marker for the development of proliferative diabetic retinopathy independently of HbA(1c), and that elevated intracellular ALE formation may be involved in the pathogenesis of this sight-threatening complication of diabetes.