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Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome.
Diabetes. 2003 Mar; 52(3):803-11.D

Abstract

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 d(3)-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 HDL(2) cholesterol (P < 0.001), HDL(3) 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.

Authors+Show Affiliations

Lipoprotein Research Unit, Department of Medicine, University of Western Australia, Royal Perth Hospital, Box X2213 GPO, Perth, WA 6847, Australia. gfwatts@cyllene.uwa.edu.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12606523

Citation

Watts, Gerald F., et al. "Differential Regulation of Lipoprotein Kinetics By Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome." Diabetes, vol. 52, no. 3, 2003, pp. 803-11.
Watts GF, Barrett PH, Ji J, et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes. 2003;52(3):803-11.
Watts, G. F., Barrett, P. H., Ji, J., Serone, A. P., Chan, D. C., Croft, K. D., Loehrer, F., & Johnson, A. G. (2003). Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes, 52(3), 803-11.
Watts GF, et al. Differential Regulation of Lipoprotein Kinetics By Atorvastatin and Fenofibrate in Subjects With the Metabolic Syndrome. Diabetes. 2003;52(3):803-11. PubMed PMID: 12606523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. AU - Watts,Gerald F, AU - Barrett,P Hugh R, AU - Ji,Juying, AU - Serone,Adrian P, AU - Chan,Dick C, AU - Croft,Kevin D, AU - Loehrer,Franziska, AU - Johnson,Anthony G, PY - 2003/2/28/pubmed PY - 2003/5/13/medline PY - 2003/2/28/entrez SP - 803 EP - 11 JF - Diabetes JO - Diabetes VL - 52 IS - 3 N2 - 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 d(3)-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 HDL(2) cholesterol (P < 0.001), HDL(3) 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. SN - 0012-1797 UR - https://www.unboundmedicine.com/medline/citation/12606523/Differential_regulation_of_lipoprotein_kinetics_by_atorvastatin_and_fenofibrate_in_subjects_with_the_metabolic_syndrome_ L2 - https://diabetes.diabetesjournals.org/lookup/pmidlookup?view=long&amp;pmid=12606523 DB - PRIME DP - Unbound Medicine ER -