Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

Abstract

OBJECTIVE:

We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B-48 and remnant-like particle (RLP)-cholesterol in postmenopausal women with type 2 diabetes mellitus.

PATIENTS AND MEASUREMENTS:

Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2-week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant-like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope-ratio mass spectrometry and multicompartmental modelling. Plasma apo B-48 and RLP-cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism.

RESULTS:

Pravastatin significantly reduced plasma concentrations of cholesterol (5.9 +/- 0.3 vs. 4.8 +/- 0.2 mmol/l; P < 0.001), low density lipoprotein (LDL)-cholesterol (3.5 +/- 0.2 vs. 2.6 +/- 0.2 mmol/l; P < 0.001), triglyceride (2.1 +/- 0.3 vs. 1.7 +/- 0.2 mmol/l; P = 0.017), non-high density lipoprotein (HDL)-cholesterol (4.4 +/- 0.3 vs. 3.3 +/- 0.2 mmol/l; P < 0.001), lathosterol/total cholesterol ratio (2.6 +/- 0.2 vs. 2.0 +/- 0.3, P = 0.035), apo B-100 (1.1 +/- 0.1 vs. 0.8 +/- 0.1 g/l; P = 0.001), apo B-48 (4.8 +/- 0.9 vs. 3.3 +/- 0.6 mg/l; P = 0.016), and RLP-cholesterol (31.4 +/- 8.2 vs. 18.6 +/- 4.6 mg/dl; P = 0.024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2.8 +/- 0.3 vs. 3.1 +/- 0.3, P = 0.029). Chylomicron remnant-like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements.

CONCLUSIONS:

In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.

• Authors: T W K Ng, G F Watts, B G A Stuckey, H L Ching, D C F Chan, Y Uchida, N Sakai, S Yamashita, I J Martins, T G Redgrave, P H R Barrett
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 63 Issue 6 Pg. 650-6 (Dec 2005) ISSN: 0300-0664 [Print] England
• PMID: 16343099 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Apolipoprotein B-48
• Apolipoproteins B
• Carbon Isotopes
• Cholesterol, LDL
• Chylomicron Remnants
• Chylomicrons
• Triglycerides
• Cholesterol
• Pravastatin

Topics

• Aged
• Anticholesteremic Agents (therapeutic use)
• Apolipoprotein B-48
• Apolipoproteins B (blood)
• Breath Tests
• Carbon Isotopes (blood)
• Cholesterol (blood)
• Cholesterol, LDL (blood)
• Chylomicron Remnants
• Chylomicrons (blood, metabolism)
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (diet therapy, drug therapy, metabolism)
• Female
• Humans
• Mass Spectrometry
• Metabolic Clearance Rate (drug effects)
• Middle Aged
• Pravastatin (therapeutic use)
• Triglycerides (blood)