Decreased basal activity of HDL associated enzyme: Paraoxonase (PON) during uncompensated oxidative stress among type 2 diabetes mellitus patients

Abstract

The inverse relationship between serum levels of High Density Lipoprotein (HDL) and the development of Cardio Vascular Disease (CVD) risk among diabetic patients was known for several decades. Besides the decreasing quantity of HDL, the qualitative functions of HDL are adversely affected during uncompensated oxidative stress among diabetics and leads to implication of several complications such as dyslipidemia, lipid peroxidation, endothelial dysfunction and atherosclerosis. Therefore we have undertaken this study to determine anti-atherogenic property of HDL by measuring it's one of the associated enzymes; paraoxonase (PON) among type 2 diabetes patients, along with the serum activity of superoxide dismutase (SOD) as an index of antioxidant status and lipid peroxidation end product, i.e malondialdehyde (MDA) as a marker for oxidative stress. This study included a total of 56 untreated type 2 diabetic patients and 29 healthy volunteers as controls. FBS, PPBS, HbA1C and fasting lipid profile were measured in both the study groups. Activity of basal PON, SOD and plasma MDA levels was determined in both the study groups according to standard clinical laboratory procedures. All the diabetic patients were under poor glycemic control. Serum levels of HDL between the two study groups are not significantly differed. But, serum basal PON and SOD activity were significantly decreased, whereas MDA levels were highly elevated (284 ± 59 nM/mL/min, 111 ± 35 μmol/L, 10.38 ± 4.17 IU/mL respectively) when compared with healthy controls (371 ± 46 nM/mL/min, 63 ± 12 μmol/L, 16.91 ± 2.89 IU/mL respectively). Although there is no significant reduction in concentrations of HDL in diabetics when compared with controls, but there was a significant decrease in anti-atherogenic property i.e. activity of paraoxonase enzyme. Moreover the serum activity of paraoxonase was significant and negatively correlated with MDA levels (r = - 0.53, P < 0.001) as well as with FBS (r = - 0.30, P < 0.05). Therefore the qualitative functions of HDL are significantly affected by hyperglycemia induced oxidative stress. Hence, we concluded that the quality of HDL is most important in order to determine oxidative stress related complications in diabetes mellitus than its concentration.