title: Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.
abstract: HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Preβ1-HDL, whereas ERN/LRP tended to lower Preβ1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements. ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered.
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain. Electronic address: luis.masana@urv.cat.
authors.forename: Luís
authors.initials: L
authors.lastname: Masana
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cabré
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Heras
authors.affiliation: Metabolomics Platform and Center for Omic Sciences, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Amigó
authors.affiliation: Metabolomics Platform and Center for Omic Sciences, Universitat Rovira i Virgili, IISPV, CIBERDEM, Reus, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Correig
authors.affiliation: Endocrinology and Nutrition Department, Hospital Clinico Universitario, CIBERDEM, INCLIVA, Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Hervás
authors.affiliation: Endocrinology and Nutrition Department, Hospital Clinico Universitario, CIBERDEM, INCLIVA, Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: José T
authors.initials: JT
authors.lastname: Real
authors.affiliation: Endocrinology and Nutrition Department, Hospital Clinico Universitario, CIBERDEM, INCLIVA, Department of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.affiliation: Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), CIBERDEM, Barcelona, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Quesada
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), CIBERDEM, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Julve
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBERDEM, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Palomer
authors.affiliation: Department of Pharmacology and Therapeutic Chemistry, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBERDEM, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Josefa
authors.initials: J
authors.lastname: Girona
authors.affiliation: Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, IISPV, Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Reus, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Plana
authors.affiliation: Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Barcelona, Spain; Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), CIBERDEM, Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Blanco-Vaca
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D053442:High-Density Lipoproteins, Pre-beta / Q000097:blood; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D016877:Oxidants / Q000097:blood; D010316:Particle Size; D011446:Prospective Studies; D019821:Simvastatin / Q000627:therapeutic use; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007211:Indoles; C518174:MK-0524; D016877:Oxidants; D009525:Niacin; D019821:Simvastatin; D011345:Fenofibrate
keywords: CETP; Fenofibrate; HDL; HDL particle size; LCAT; Niacin; Nuclear magnetic resonance; PAF-AH; PON1; PON3; Preβ1-HDL; Type 2 diabetes