HDL biology
High-dose atorvastatin reduces pre-beta-HDL formation and CETP activity in type 2 diabetes, mediated by falling PLTP activity and triglycerides, not CETP (Biochim Biophys Acta 2009)
Original title: Plasma pre beta-HDL formation is decreased by atorvastatin treatment in type 2 diabetes mellitus: Role of phospholipid transfer protein
In the DALI study, plasma pre-beta-HDL formation, apolipoprotein A-I, LpA, LpAI:AII, cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP) activity were measured before and after 30 weeks of treatment in 40 patients randomized to atorvastatin 80 mg daily and 41 patients receiving placebo. Plasma pre-beta-HDL formation, triglycerides, LDL cholesterol, PLTP activity, and CETP all decreased after statin treatment (all P<0.001 versus placebo), while HDL cholesterol increased (P<0.005); apolipoprotein A-I, LpAI, and LpAI:AII were unchanged. Across all patients, changes in pre-beta-HDL formation were independently related to decreases in triglycerides (beta=0.31; P=0.006) and PLTP activity (beta=0.23; P=0.038), with no contribution from CETP. High-dose atorvastatin therefore decreases pre-beta-HDL generation capacity in type 2 diabetes, likely via lowering PLTP activity and triglycerides.
Original abstract
Unlabelled: Atorvastatin lowers plasma phospholipid transfer protein (PLTP) activity, which stimulates pre-beta-HDL generation in vitro. We determined the effect of atorvastatin on pre-beta-HDL formation and its relation with PLTP activity in type 2 diabetes.
Methods: Plasma pre-beta-HDL formation as well as plasma apo A-I, LpA, LpAI:AII, cholesteryl ester transfer protein (CETP) and PLTP activity were measured before and after 30 weeks treatment in 40 patients randomized to atorvastatin 80 mg daily and 41 placebo receiving patients. Pre-beta HDL formation was measured by crossed immunoelectrophoresis under conditions of lecithin:cholesterol acyltransferase (LCAT) inhibition.
Results: Plasma pre-beta-HDL formation, triglycerides, LDL cholesterol, PLTP activity, and CETP decreased after statin treatment (all P<0.001 vs placebo), whereas HDL cholesterol increased (P<0.005). Plasma apo A-I, LpAI and LpAI:AII remained unchanged compared to placebo. In all patients combined, the changes in pre-beta-HDL formation were independently related to the decrease in plasma triglycerides (beta=0.31; P=0.006) and PLTP activity (beta=0.23; P=0.038), without a contribution of CETP. In the atorvastatin treated patients, the decrease in pre-beta-HDL formation tended to be related to the decrease in PLTP activity (beta=0.30, P=0.061) after controlling for decreases in triglycerides (beta=0.22, P=0.22).
Conclusion: High dose atorvastatin decreases the capacity of plasma to generate pre-beta-HDL particles in type 2 diabetic patients, probably via lowering of plasma PLTP activity and triglycerides. This could contribute to an improvement in the atherogenic lipoprotein profile.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.