Oxidative stress and high-density lipoprotein function in Type I diabetes and end-stage renal disease

In a cross-sectional study, oxidative stress in high vascular disease risk groups, ESRD (end-stage renal disease) and Type I diabetes, was assessed by measuring plasma protein carbonyls and comparing antioxidant capacity of HDL (high-density lipoprotein) as pertaining to PONI (paraoxonase I) activity and in vitro removal of LPO (lipid peroxides). ESRD subjects on haemodialysis (n = 22), Type I diabetes subjects (n = 20) without vascular complications and healthy subjects (n = 23) were compared. Plasma protein carbonyls were higher in ESRD patients [0.16 (0.050) nmol/mg of protein; P = 0.001; value is mean (SD)] relative to subjects with Type I diabetes [0.099 (0.014) nmol/mg of protein] and healthy subjects [0.093 (0.014) nmol/mg of protein]. Plasma PONI activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PONI activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PONI activity and plasma protein carbonyl concentrations were inversely related (r = -0.50, P < 0.05). In an in vitro assay, LPO removal by HDL in ESRD subjects was greater than HDL from healthy subjects (P < 0.01), whereas HDL from patients with Type I diabetes was less effective (P < 0.01). Efficacy of LPO removal was unrelated to plasma PONI activity, in vitro glycation or mild oxidation, but was impaired by marked oxidation and glycoxidation. Protein carbonyl levels are increased in ESRD but not in complication-free Type I diabetes. HDL antioxidant function is increased in ESRD, perhaps a compensatory response to increased oxidative stress, but is lower in Type I diabetes. HDL dysfunction is related to glycoxidation rather than glycation or PONI activity. © 2005 The Biochemical Society.