Plasma phospholipid transfer protein activity is independently determined by obesity and insulin resistance in non-diabetic subjects

Phospholipid transfer protein (PLTP) is an emerging cardio-metabolic risk factor which is intricately involved in lipoprotein metabolism. Elevated plasma PLTP activity levels are reported in obesity and diabetes mellitus, but the relative contributions of obesity and insulin resistance to plasma PLTP activity remain unclear. We tested whether plasma PLTP activity is independently related to (central) obesity and insulin resistance in non-diabetic subjects. The relationships of plasma PLTP activity levels (phospholipid vesicles-HDL system) with waist circumference, waist/hip ratio, body mass index (BMI) and insulin resistance (homeostasis model assessment (HOMA(ir))) were determined in 313 non-diabetic subjects (273 men). PLTP activity was higher in 67 subjects with enlarged waist circumference (NCEP-ATP-III criteria; 102 ± 11 AU) compared to 246 subjects with normal waist (98 ± 11 AU, P=0.027). In univariate analysis PLTP activity correlated positively with waist (r=0.188), waist/hip ratio (r=0.143), BMI (r=0.125) and HOMA(ir) (r=0.192) (P <0.05 to P <0.001). The relationship of PLTP with HOMA(ir) was confined to subjects with the highest waist circumference and waist/hip ratio. In age- and sex-adjusted multiple linear regression models, waist circumference (β=0.158, P=0.025), but not BMI, predicted PLTP activity independently of HOMA(ir) (β=0.126, P=0.047). Furthermore, both waist and waist/hip ratio interacted positively with HOMA(ir) on PLTP activity (β=0.109, P=0.056 and β=0.156, P=0.034, respectively). In non-diabetic subjects, both obesity and insulin resistance influence plasma PLTP activity, resulting in elevated plasma PLTP activity particularly with combined increases in obesity and insulin resistance. Higher PLTP activity could contribute to elevated cardiovascular risk in the presence of obesity and insulin resistance