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- Title
Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?
- Authors
Ng, T. W. K.; Watts, G. F.; Stuckey, B. G. A.; Ching, H. L.; Chan, D. C. F.; Uchida, Y.; Sakai, N.; Yamashita, S.; Martins, I. J.; Redgrave, T. G.; Barrett, P. H. R.
- 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.
- Subjects
PRAVASTATIN; STATINS (Cardiovascular agents); METABOLISM; DIABETES in women; TREATMENT of diabetes; THERAPEUTICS; ENDOCRINOLOGY
- Publication
Clinical Endocrinology, 2005, Vol 63, Issue 6, p650
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/j.1365-2265.2005.02396.x