Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Watts, G. F.
Right arrow Articles by Johnson, A. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watts, G. F.
Right arrow Articles by Johnson, A. G.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 52:803-811, 2003
© 2003 by the American Diabetes Association, Inc.

Differential Regulation of Lipoprotein Kinetics by Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome

Gerald F. Watts1, P. Hugh R. Barrett1, Juying Ji1, Adrian P. Serone2, Dick C. Chan1, Kevin D. Croft1, Franziska Loehrer2, and Anthony G. Johnson2

1 Lipoprotein Research Unit, Department of Medicine, University of Western Australia, the West Australian Institute for Medical Research, Perth, Western Australia
2 James Lance GlaxoSmithKline Medicines Research Unit, Prince of Wales Hospital, Sydney, Australia

The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d3-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL2 cholesterol (P < 0.001), HDL3 cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Diabetes CareHome page
T. W.K. Ng, G. F. Watts, P. H. R. Barrett, K.-A. Rye, and D. C. Chan
Effect of Weight Loss on LDL and HDL Kinetics in the Metabolic Syndrome: Associations with changes in plasma retinol-binding protein-4 and adiponectin levels
Diabetes Care, November 1, 2007; 30(11): 2945 - 2950.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. Lamon-Fava, M. R. Diffenderfer, P. H. R. Barrett, A. Buchsbaum, N. R. Matthan, A. H. Lichtenstein, G. G. Dolnikowski, K. Horvath, B. F. Asztalos, V. Zago, et al.
Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism
J. Lipid Res., August 1, 2007; 48(8): 1746 - 1753.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
S. E. Nissen, S. J. Nicholls, K. Wolski, D. C. Howey, E. McErlean, M.-D. Wang, E. V. Gomez, and J. M. Russo
Effects of a Potent and Selective PPAR-{alpha} Agonist in Patients With Atherogenic Dyslipidemia or Hypercholesterolemia: Two Randomized Controlled Trials
JAMA, March 28, 2007; 297(12): 1362 - 1373.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. Rashid, B. W. Patterson, and G. F. Lewis
Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans?
J. Lipid Res., August 1, 2006; 47(8): 1631 - 1642.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. G. Parhofer and P. H. R. Barrett
Thematic review series: Patient-Oriented Research. What we have learned about VLDL and LDL metabolism from human kinetics studies
J. Lipid Res., August 1, 2006; 47(8): 1620 - 1630.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
P. H. R. Barrett, D. C. Chan, and G. F. Watts
Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans
J. Lipid Res., August 1, 2006; 47(8): 1607 - 1619.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
D. C Chan, G. F Watts, M. N Nguyen, and P H. R Barrett
Factorial study of the effect of n-3 fatty acid supplementation and atorvastatin on the kinetics of HDL apolipoproteins A-I and A-II in men with abdominal obesity
Am. J. Clinical Nutrition, July 1, 2006; 84(1): 37 - 43.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Ji, G. F. Watts, A. G. Johnson, D. C. Chan, E. M. M. Ooi, K.-A. Rye, A. P. Serone, and P. H. R. Barrett
High-Density Lipoprotein (HDL) Transport in the Metabolic Syndrome: Application of a New Model for HDL Particle Kinetics
J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 973 - 979.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. N. Ginsberg
REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 383 - 392.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
W. L. Isley, J. M. Miles, B. W. Patterson, and W. S. Harris
The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus
J. Lipid Res., January 1, 2006; 47(1): 193 - 200.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Myerson, C. Ngai, J. Jones, S. Holleran, R. Ramakrishnan, L. Berglund, and H. N. Ginsberg
Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia
J. Lipid Res., December 1, 2005; 46(12): 2735 - 2744.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
K. Bach-Ngohou, K. Ouguerram, R. Frenais, P. Maugere, B. Ripolles-Piquer, Y. Zair, M. Krempf, and J. M. Bard
Influence of Atorvastatin on Apolipoprotein E and AI Kinetics in Patients with Type 2 Diabetes
J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 363 - 369.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. S. Millar, C. Maugeais, K. Ikewaki, D. M. Kolansky, P.H. R. Barrett, E. C. Budreck, R. C. Boston, N. Tada, S. Mochizuki, J. C. Defesche, et al.
Complete Deficiency of the Low-Density Lipoprotein Receptor Is Associated With Increased Apolipoprotein B-100 Production
Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 560 - 565.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
H. Duez, B. Lefebvre, P. Poulain, I. P. Torra, F. Percevault, G. Luc, J. M. Peters, F. J. Gonzalez, R. Gineste, S. Helleboid, et al.
Regulation of Human ApoA-I by Gemfibrozil and Fenofibrate Through Selective Peroxisome Proliferator-Activated Receptor {alpha} Modulation
Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 585 - 591.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. S. Birjmohun, B. A. Hutten, J. J.P. Kastelein, and E. S.G. Stroes
Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: A meta-analysis of randomized controlled trials
J. Am. Coll. Cardiol., January 18, 2005; 45(2): 185 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
G. M. Dallinga-Thie, I. I.L. Berk-Planken, A. H. Bootsma, and H. Jansen
Atorvastatin Decreases Apolipoprotein C-III in Apolipoprotein B-Containing Lipoprotein and HDL in Type 2 Diabetes: A potential mechanism to lower plasma triglycerides
Diabetes Care, June 1, 2004; 27(6): 1358 - 1364.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
G. F Watts
Treating low HDL-cholesterol in normocholesterolaemic patients with coronary disease: statins, fibrates or horses for courses?
Eur. Heart J., May 1, 2004; 25(9): 716 - 719.
[Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. Bilz, S. Wagner, M. Schmitz, A. Bedynek, U. Keller, and T. Demant
Effects of atorvastatin versus fenofibrate on apoB-100 and apoA-I kinetics in mixed hyperlipidemia
J. Lipid Res., January 1, 2004; 45(1): 174 - 185.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
B. E. Aouizerat and J. P. Kane
Apolipoprotein A-II: Active or Passive Role in Familial Combined Hyperlipidemia
Circ. Res., June 13, 2003; 92(11): 1179 - 1181.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2003 by the American Diabetes Association.