Paraoxonase-1 activity is positively related to phospholipid transfer protein activity in type 2 diabetes mellitus: Role of large HDL particles

High density lipoprotein (HDL)-associated paraoxonase-1 (PON-1) exerts anti-oxidative properties, whereas phospholipid transfer protein (PLTP) is able to convert mature HDL into larger and smaller HDL particles. Here we tested associations of PON-1 with PLTP in type 2 diabetes mellitus (T2DM), a condition characterized by lower PON-1 activity and higher PLTP activity. Serum PON-1 (arylesterase activity), plasma PLTP activity (liposome-vesicle HDL system), and (apo)lipoproteins were measured in 81 T2DM subjects (mean age 59±9years; 31 women; no insulin treatment). In 48 participants, HDL subfractions were measured by nuclear magnetic resonance spectroscopy. In univariate correlation analysis, PON-1 activity was positively related to PLTP activity (r=0.348, p=0.001). PLTP activity was positively related to blood pressure, body mass index and triglycerides, whereas PON-1 activity was positively to HDL cholesterol and apoA-I (p <0.05 to <0.01 for each). Both PLTP activity and PON-I activity were positively related to large HDL particles (r=0.379, p=0.008 and r=0.411, p=0.004, respectively). In multivariable linear regression analysis, PON-1 activity was associated with PLTP activity independent of clinical covariates and HDL cholesterol or apoA-I (β=0.340, p=0.001 and β=0.320, p=0.003, respectively). The association of PON-1 activity with PLTP activity was lost in analysis which included large HDL particles (large HDL: β=0.411, p=0.004). PON-1 activity is positively related to PLTP activity in T2DM, raising the possibility that PLTP could act to maintain PON-1. This association may in part be attributable to a common relationship of PON-1 and PLTP with large HDL particles