Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL

Abstract

Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellitus and aimed to identify potential determinants of this parameter. In a cross-sectional study, we investigated 74 patients with type 2 diabetes and 75 control subjects. Antioxidative properties of HDL were measured and expressed as either (i) HDL antioxidative capacity or (ii) HDL antioxidation index after multiplying HDL antioxidative capacity results with individual plasma HDL cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) and paraoxonase-1 (PON-1) activities were determined. HDL antioxidative capacity was similar in patients with diabetes and controls, while the HDL antioxidation index was decreased in patients with diabetes (P = 0.005) owing to lower plasma HDL cholesterol (P < 0.001). LCAT activity was higher and PON-1 activity lower in type 2 diabetes mellitus (each P < 0.001). In the combined subjects, HDL antioxidative capacity was inversely related to LCAT activity (P < 0.01). The HDL antioxidation index correlated negatively with blood glucose (P < 0.001), HbA1c and LCAT activity (each P < 0.01), and positively with PON-1 activity (P < 0.01). Multiple linear regression analysis demonstrated that high LCAT activity was associated with both decreased HDL antioxidation capacity (P < 0.05) and index (P < 0.001) independent of diabetes status, glycaemic control and PON-1. Overall, the antioxidative functionality of HDL is impaired in type 2 diabetes mellitus mostly because of lower HDL cholesterol. Hyperglycaemia, increased LCAT activity and lower PON-1 activity likely contribute to impaired antioxidative functionality of HDL.