Reduction of paraoxonase-1 activity may contribute the qualitative impairment of HDL particles in patients with type 2 diabetes

Abstract

Aims: Cholesterol efflux with high-density lipoprotein (HDL) particles has an important role in the first step of reverse cholesterol transport (RCT). However, HDL function in type 2 diabetes has not been well investigated thoroughly. We measured cholesterol efflux in 36 patients with type 2 diabetes compared with 9 controls without diabetes.

Methods: The HDL fraction was separated with polyacrylamide gel and recovered using the protein recovery system. Concentration adjusted HDL fraction was used to determine HDL-mediated cholesterol efflux (Efflux-hdl) from THP-1 derived macrophages. We measured paraoxonase-1 (PON 1) activity to determine antioxidation capacity, serum amyloid A protein (SAA) to determine inflammatory response, and carboxymethyl-lysin (CML) to determine antiglucoxidative capacity.

Results: Efflux-hdl demonstrated no correlation with plasma apoprotein A-1 (ApoA-I) or HDL-cholesterol in patients with diabetes. PON1 activity in the patients' HDL fraction was positively correlated with Efflux-hdl (r=0.39, p=0.02), and showed a negative tendency with HbA1c levels (r=-0.28, p=0.10). SAA and CML levels did not demonstrate correlation with Efflux-hdl in patients with diabetes.

Conclusion: We confirmed the functional changes in HDL particles in the patients. Efflux-hdl from macrophages was reduced depending upon the decrease in PON1 activity, which was inversely related to HbA1c levels.