Abstract 6274: Heterogeneous Postprandial Lipoprotein and Inflammatory Responses in the Metabolic Syndrome, and Response to FenofibrateTherapy
Describe heterogeneous postprandial responses in subjects with elevated fasting triglycerides (TG≥1.7 mmol/L and <6.9 mmol/L) and the MetS, and investigate the effects of fenofibrate (160 mg/d) on postprandial TG-containing lipoproteins and inflammatory markers in subjects with early (3.5 h) versus late (8 h) postprandial TG responses. Fifty-five subjects (41 M, 14 F) with high TG and two or more of the ATP III criteria of the MetS were randomized to fenofibrate (160 mg/d) or placebo in a double-blind controlled clinical trial. A standardized fat load (50 g/m2) was given orally after a 12 h fast. Blood specimens were obtained at 0 h (fasting), 3.5 h, and 8 h after the test meal. High TG subjects with the MetS exhibited variable postprandial lipoprotein responses with maximal postprandial TG concentration at 3.5 h in 28 subjects (early TG peakers) and at 8 hours in 23 subjects (late TG peakers). Late TG peakers were significantly older (57.4 ± 7.6 y vs. 50.5 ± 10.9 y, p=0.02), but they were not different in other clinical characteristics including HOMA index (p=0.66). Postprandial (AUC/8 h) TG concentrations were higher among late TG peakers than early TG peakers (39.7 mmol/L vs. 27.9 mmol/L, p=0.013) attributable to in part higher NMR-measured large VLDL particle levels (162 nmol/L vs. 115 nmol/L, p=0.015). Postprandial ICAM-1 levels were no different between late TG peakers vs. early TG peakers (p=0.75). Fenofibrate was more effective in late TG than early TG peakers in reducing postprandial TG concentrations (−67% vs. −34%, p=0.0024) and large VLDL (−76% vs. −31%, p=0.0016). Late TG peakers also had larger postprandial reduction in circulating ICAM-I levels with fenofibrate therapy (−23% vs. −11%, p=0.045). Late postprandial TG responders have attenuated clearance of large VLDL particles. Despite the more abnormal postprandial TG responses, late TG peakers were more responsive to the lipoprotein and anti-inflammatory effects of fenofibrate therapy.