HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs
for the treatment of dyslipidemia in patients with type 2 diabetes mellitus.
We conducted a randomized, double-blind, placebo-controlled, crossover
design trial to determine the effects of simvastatin, 80 mg/day, on plasma
lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB)
in VLDL, intermediate density lipoprotein (IDL), and LDL and of
triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol,
and apoB significantly in VLDL, IDL, and LDL.
These effects were associated with reduced production of LDL-apoB, mainly as
a result of reduced secretion of apoB-lipoproteins directly into the LDL
density range. Statin therapy also reduced hepatic production of VLDL-TG.
There were no effects of simvastatin on the fractional catabolic rates of
VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion
during simvastatin treatment is not clear, but recent studies suggest that
statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha).
Activation of PPARalpha could lead to increased hepatic oxidation of fatty
acids and less synthesis of TG for VLDL assembly.
Reference:
J Lipid Res. 2005 Dec;46(12):2735-44 |