Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

• Published in: Diabetes care Vol. 30; no. 8; pp. 1945 - 1951
• Main Authors: Rosenson, Robert S, Wolff, David A, Huskin, Anna L, Helenowski, Irene B, Rademaker, Alfred W
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2007
• Subjects: adhesion; Adult; adults; Apolipoproteins B; Apolipoproteins B - blood; Biological and medical sciences; blood; Blood Glucose; Blood Glucose - metabolism; Blood Pressure; cell adhesion; Changes; Cholesterol; clinical trials; complications; Diet; Double-Blind Method; Drug therapy; Endocrinopathies; fasting; fatty acids; Fatty Acids, Nonesterified; Fatty Acids, Nonesterified - blood; Feeding. Feeding behavior; Female; Fenofibrate; Fenofibrate - therapeutic use; Field study; free fatty acids; Fundamental and applied biological sciences. Psychology; Heart attacks; Hormone replacement therapy; Humans; Hyperlipidemia; hypertriglyceridemia; Hypertriglyceridemia - blood; Hypertriglyceridemia - complications; Hypertriglyceridemia - drug therapy; Hypolipidemic Agents; Hypolipidemic Agents - therapeutic use; Hypothyroidism; inflammation; Insulin; Insulin - blood; Intercellular Adhesion Molecule-1; Intercellular Adhesion Molecule-1 - blood; Lipids; Lipids - blood; Lipoproteins; Lipoproteins - blood; low density lipoprotein; Male; Medical sciences; Metabolic syndrome; Metabolic Syndrome - blood; Metabolic Syndrome - complications; Metabolic Syndrome - drug therapy; Metabolic syndrome X; metabolism; Middle Aged; Mortality; NMR; Nuclear magnetic resonance; Nutrition; oxidation; Oxidative Stress; Patient Selection; Placebos; Plasma; Postmenopause; Risk factors; Smoking; therapeutic use; therapeutics; triacylglycerols; Vascular Cell Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1 - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; very low density lipoprotein; United States; Endocrinopathy; Human; Oxidative stress; Therapy; Fasting; Nutrition; Fibrate derivatives; Postprandial; Cardiovascular disease; Lipids; Metabolic diseases; Hyperlipoproteinemia; Inflammation; Lipoprotein; Triglyceride; Enzymopathy; Fenofibrate; Treatment; Hypertriglyceridemia; X Syndrome; Dyslipemia; Fast; Endocrinology; Antilipemic agent
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc07-0015

OBJECTIVE:--The aim of this study was to determine the effects of fenofibrate (160 mg/day) on fasting and postprandial lipoproteins, oxidized fatty acids, and inflammatory mediators in subjects with hypertriglyceridemia and the metabolic syndrome. RESEARCH DESIGN AND METHODS--Fifty-nine subjects with fasting hypertriglyceridemia (>=1.7 and <6.9 mmol/l) and two or more of the Adult Treatment Panel III criteria for the metabolic syndrome were randomly assigned to fenofibrate (160 mg/day) or placebo in a double-blind, controlled clinical trial. RESULTS:--Fenofibrate treatment lowered fasting triglycerides (-46.1%, P < 0.0001) and postprandial (area under the curve) triglycerides (-45.4%, P < 0.0001) due to significant reductions in postprandial levels of large (-40.8%, P < 0.0001) and medium (-49.5%, P < 0.0001) VLDL particles. The number of fasting total LDL particles was reduced in fenofibrate-treated subjects (-19.0%, P = 0.0033) primarily due to reductions in small LDL particles (-40.3%, P < 0.0001); these treatment differences persisted postprandially. Fasting and postprandial oxidized fatty acids were reduced in fenofibrate-treated subjects compared with placebo-administered subjects (-15.3%, P = 0.0013, and 31.0%, P < 0.0001, respectively), and fenofibrate therapy lowered fasting and postprandial soluble vascular cell adhesion molecule-1 (VCAM-1) (-10.9%, P = 0.0005, and -12.0%, P = 0.0001, respectively) as well as fasting and postprandial soluble intercellular adhesion molecule-1 (ICAM-1) (-14.8%, P < 0.0001, and -15.3%, P < 0.0001, respectively). Reductions in VCAM-1 and ICAM-1 were correlated with reductions in fasting and postprandial large VLDL particles (P < 0.0001) as well as postprandial oxidized fatty acids (P < 0.0005). CONCLUSIONS:--Triglyceride-lowering therapy with fenofibrate reduced fasting and postprandial free fatty acid oxidation and inflammatory responses, and these antiatherosclerotic effects were most highly correlated with reductions in large VLDL particles.