Protective effect of paraoxonase 1 of high‐density lipoprotein in type 2 diabetic patients with nephropathy

Abstract

Paraoxonase 1 (PON1) is an important antioxidative enzyme associated with high-density lipoproteins (HDL). Recent data suggest that HDL antioxidative ability may be altered in type 2 diabetic patients. The aim of this study was, therefore, to investigate whether HDL-PON1 activity and HDL antioxidative ability were related to the presence and severity of diabetic nephropathy. Sixty type 2 diabetic patients, who were subdivided into normoalbuminuria, microalbuminuria and macroalbuminuria, and 20 age- and sex-matched healthy controls were recruited. HDL was then isolated to measure PON1 activity, lipid peroxide and its ability in protecting low-density lipoprotein (LDL) from oxidation. HDL-PON1 activity and HDL antioxidative ability in protecting LDL from oxidation was preserved in diabetic patients with normoalbuminuria, but significantly decreased in those with microalbuminuria or macroalbuminuria. HDL peroxide was comparable between healthy controls and normoalbuminuric patients, but significantly increased in those with microalbuminuria or macroalbuminuria. On multiple analyses, urinary protein was an independent negative determinant of HDL-PON1 activity, and HDL-PON1 activity was positively associated with HDL antioxidative ability, and negatively associated with HDL peroxide. HDL-PON1 activity is decreased in type 2 diabetic patients with incipient or overt nephropathy, which relates to the reduced HDL antioxidative ability in protecting LDL from oxidation and increased peroxide in HDL.