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


METHODS
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.
Ng
T W K
TW
School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, Perth, Australia.
Watts
G F
GF
Stuckey
B G A
BG
Ching
H L
HL
Chan
D C F
DC
Uchida
Y
Y
Sakai
N
N
Yamashita
S
S
Martins
I J
IJ
Redgrave
T G
TG
Barrett
P H R
PH
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood; D001944:Breath Tests; D002247:Carbon Isotopes / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002247:Carbon Isotopes; D008078:Cholesterol, LDL; D053298:Chylomicron Remnants; D002914:Chylomicrons; D014280:Triglycerides; D002784:Cholesterol; D017035:Pravastatin