title: Effects of extended-release niacin on the postprandial metabolism of Lp(a) and ApoB-100-containing lipoproteins in statin-treated men with type 2 diabetes mellitus.
abstract: OBJECTIVE
  The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration.
  
  
  RESULTS
  The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%).
  
  
  CONCLUSIONS
  In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Esther M
authors.initials: EM
authors.lastname: Ooi
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Tenneti
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hamilton
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Sally P
authors.initials: SP
authors.lastname: McCormick
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.).
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.affiliation: From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia (E.M.O., G.F.W., D.C.C., J.P., V.S.T., P.H.R.B.); Lipid Disorders Clinic, Cardiometabolic Service, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia (G.F.W.); Western Australian Centre for Rural Health, University of Western Australia, Geraldton, Australia (S.J.H.); Department of Biochemistry, University of Otago, Dunedin, New Zealand (S.P.M.); Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle (S.M.M.); and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia (P.H.R.B.). hugh.barrett@uwa.edu.au.
authors.forename: P Hugh R
authors.initials: PH
authors.lastname: Barrett
mesh_terms: D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood*; D001054:Apolipoproteins A / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D004041:Dietary Fats / Q000097:blood; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D017270:Lipoprotein(a) / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009525:Niacin / Q000627:therapeutic use*; D019518:Postprandial Period; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D053299:Apolipoprotein B-100; D001054:Apolipoproteins A; D015415:Biomarkers; D003692:Delayed-Action Preparations; D004041:Dietary Fats; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D009525:Niacin; D000068718:Rosuvastatin Calcium
keywords: cardiovascular disease risk; kinetics; lipoprotein; lipoprotein(a); type 2 diabetes mellitus