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Abstract
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.
Highlights
HMG-CoA reductase inhibitors are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus
Inhibition of cholesterol synthesis leads to increased levels of LDL receptors, in the liver [21, 22], and this is consistent with an increased fractional clearance rate (FCR; a measure of the efficiency with which a lipoprotein is cleared from plasma) of LDL-apolipoprotein B (apoB) observed during statin treatment of patients with familial hypercholesterolemia [23]
Increased fractional clearance of VLDL by statininduced hepatic LDL receptors might account for the lower plasma VLDL concentrations seen, reduced production rates (PRs) of VLDL-apoB and -TG (PR will be used to represent the secretion of apoB and TG from the liver under the conditions of our studies) have been demonstrated in several studies of statin therapy in patients with increased plasma VLDL concentrations
Summary
HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. Increased fractional clearance of VLDL by statininduced hepatic LDL receptors might account for the lower plasma VLDL concentrations seen, reduced production rates (PRs) of VLDL-apoB and -TG (PR will be used to represent the secretion of apoB and TG from the liver under the conditions of our studies) have been demonstrated in several studies of statin therapy in patients with increased plasma VLDL concentrations. Because overproduction of apoB-lipoproteins is characteristic of the dyslipidemia of diabetes, we undertook a randomized, double-blind, crossover study of the effects of high-dose simvastatin therapy on the PRs and FCRs of VLDL-, intermediate density lipoprotein (IDL)-, and LDL-apoB and VLDL-TG in patients with T2DM
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