Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, decreases cholesteryl ester transfer protein in type 2 diabetes mellitus.

Abstract

To address the effects of ezetimibe on high-density lipoprotein (HDL) metabolism, the HDL subclasses, cholesteryl ester transfer protein (CETP), and lecithin-cholesterol acyltransferase (LCAT) were measured in patients with type 2 diabetes mellitus (T2DM). Twenty-three hypercholesterolemic patients with T2DM were treated with 10 mg of ezetimibe daily for 12 weeks. Plasma total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol (C), HDL-C, HDL(2)-C, HDL(3)-C, CETP mass, and LCAT activity were measured. HDL-C and HDL(2)-C increased by 5% (p<0.05) and 12% (p<0.01), respectively, in response to ezetimibe. Of the 23 patients, 21 had decreased CETP mass, which led to an average reduction of 20% (p<0.0001). LCAT activity also decreased by 6% (p<0.01). A significant positive correlation was found in the changes from baseline between HDL(2)-C and CETP mass, whereas a significant inverse relationship was observed between HDL(3)-C and CETP mass. Furthermore, the change in HDL-C was positively correlated with the change in LCAT activity. In conclusion, ezetimibe may affect HDL metabolism and reverse cholesterol transport, especially CETP, in T2DM. These observations may provide some insights into how ezetimibe prevents atherosclerosis.

• Authors: Hiroaki Yagyu, Shuichi Nagashima, Manabu Takahashi, Michiaki Miyamoto, Kenta Okada, Jun-Ichi Osuga, Shun Ishibashi
• Journal: Endocrine journal (Endocr J) Vol. 59 Issue 12 Pg. 1077-84 ( 2012) ISSN: 1348-4540 [Electronic] Japan
• PMID: 22850130 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Carrier Proteins
• Cholesterol Ester Transfer Proteins
• Cholesterol, HDL
• Intracellular Signaling Peptides and Proteins
• Lipoproteins, HDL
• Membrane Glycoproteins
• NPC1 protein, human
• Niemann-Pick C1 Protein
• Phosphatidylcholine-Sterol O-Acyltransferase
• Ezetimibe

Topics

• Aged
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Azetidines (pharmacology, therapeutic use)
• Carrier Proteins (antagonists & inhibitors)
• Cholesterol Ester Transfer Proteins (blood, metabolism)
• Cholesterol, HDL (blood, metabolism)
• Diabetes Mellitus, Type 2 (blood, drug therapy, metabolism)
• Down-Regulation (drug effects)
• Ezetimibe
• Female
• Humans
• Intracellular Signaling Peptides and Proteins
• Lipoproteins, HDL (blood, metabolism)
• Male
• Membrane Glycoproteins (antagonists & inhibitors)
• Middle Aged
• Niemann-Pick C1 Protein
• Phosphatidylcholine-Sterol O-Acyltransferase (blood, metabolism)