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

Department of Medicine, The University of Melbourne, St. Vincent's Hospital, Fitzroy, 3065 Melbourne, Australia.
Clinical Science (Impact Factor: 5.6). 06/2005; 108(6):497-506. DOI: 10.1042/CS20040312
Source: PubMed


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 PON1 (paraoxonase 1) 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 PON1 activity, with and without correction for HDL-cholesterol, was lower in diabetes but did not differ in ESRD compared with healthy subjects. Plasma PON1 activity, without correction for HDL, did not differ between the three groups. In ESRD, plasma PON1 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 PON1 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 PON1 activity.

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    • "the plasma proteins, have often been controversial. Whereas some studies (Telci et al., 2000; Martin-Gallan et al. 2003) showed pathologically increased plasma protein carbonylation in complication-free type 1 and type 2 diabetic patients, other studies reported opposite results (Odetti et al., 1999; Kalogerakis et al., 2005). Furthermore, an interrelation between protein carbonyl levels and the development of diabetic complications has been reported for microangiopathy cases (Konukoglu et al., 2002; Adaikalakoteswari et al., 2006) but rarely for a diabetic retinopathy group of patients (Pan et al., 2008), further subdivided according to the clinical forms of the disease. "
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