The specific impact of
3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors and
fibrates on the in vivo metabolism of
apolipoprotein (
apo) B has not been systematically investigated in patients with
type 2 diabetes mellitus with high plasma
triglyceride (TG) levels. Therefore, the objective of this 2-group parallel study was to examine the differential effects of a 6-week treatment with
atorvastatin or
fenofibrate on in vivo kinetics of
apo B-48 and B-100 in men with
type 2 diabetes mellitus with marked
hypertriglyceridemia.
Apolipoprotein B kinetics were assessed at baseline and at the end of the intervention using a primed constant infusion of [5,5,5-D(3)]-
l-leucine for 12 hours in the fed state.
Fenofibrate significantly decreased plasma TG levels with no significant change in plasma
low-density lipoprotein cholesterol (
LDL-C) and
apo B levels. On the other hand,
atorvastatin significantly reduced plasma levels of TG,
LDL-C, and
apo B.
After treatment with
fenofibrate,
very low-density lipoprotein (VLDL)
apo B-100 pool size (PS) was decreased because of an increase in the fractional catabolic rate (FCR) of VLDL
apo B-100. No significant change was observed in the kinetics of
LDL apo B-100. Moreover,
fenofibrate significantly decreased TG-rich
lipoprotein (TRL)
apo B-48 PS because of a significant increase in TRL
apo B-48 FCR.
After treatment with
atorvastatin, VLDL and IDL
apo B-100 PSs were significantly decreased because of significant elevations in the FCR of these subfractions.
Low-density lipoprotein apo B-100 PS was significantly lowered because of a tendency toward decreased
LDL apo B-100 production rate (PR). Finally,
atorvastatin reduced TRL
apo B-48 PS because of a significant decrease in the PR of this subfraction. These results indicate that
fenofibrate increases TRL
apo B-48 as well as VLDL
apo B-100 clearance in men with
type 2 diabetes mellitus with marked
hypertriglyceridemia, whereas
atorvastatin increases both VLDL and IDL
apo B-100 clearance and decreases TRL
apo B-48 and
LDL apo B-100 PR.