title: A pilot study of ezetimibe vs. atorvastatin for improving peripheral microvascular endothelial function in stable patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Elevated cholesterol in type 2 diabetes mellitus (DM) can cause endothelial dysfunction. An effective clinical therapy to improve endothelial dysfunction remains to be established. Different cardiovascular actions between treatments for the inhibition of cholesterol absorption and the suppression of cholesterol synthesis for achieving improvement in endothelial function are unknown in DM.
  
  
  METHODS
  Stable patients with type 2 DM and mildly elevated low-density lipoprotein cholesterol were enrolled. We evaluated peripheral microvascular endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT) examination and calculated a natural logarithmic transformed value for the RH-PAT index (LnRHI). We randomly assigned 33 patients to each monotherapy: cholesterol synthesis suppression using atorvastatin (5 mg/day, n=16) or cholesterol absorption inhibition using ezetimibe (10 mg/day, n=17). Patients were prospectively followed for 6 months. Serum lipids and LnRHI were repeatedly examined before and after each therapy.
  
  
  RESULTS
  LDL significantly decreased in both groups, but the percent changes of LDL showed a greater decrease in the atorvastatin group compared with the ezetimibe group (-34.5±7.8% vs. -21.9±9.6%, p<0.01). Serum levels of non-esterified free fatty acids (NEFA) significantly decreased in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 561.1±236.8 to 429.7±195.9, p<0.01; atorvastatin group: 538.8±319.5 to 520.2±227.3, p=0.75). The percent decrease in NEFA was significantly greater in the ezetimibe group compared with the atorvastatin group (-19.9±27.4% vs. 11.3±44.1%, p<0.05). LnRHI showed a significant increase in the ezetimibe group but not in the atorvastatin group (ezetimibe group: 0.471±0.157 to 0.678±0.187, p<0.01; atorvastatin group: 0.552±0.084 to 0.558±0.202, p=0.64). The percent changes in LnRHI were significantly greater in the ezetimibe group compared with the atorvastatin group (63.3±89.2% vs. 7.4±41.2%, p<0.05).
  
  
  CONCLUSIONS
  In patients with type 2 DM, ezetimibe monotherapy significantly reduced LDL and NEFA, and improved peripheral microvascular endothelial dysfunction. Ezetimibe could potentially exhibit beneficial effects on lipid disorders and microvascular endothelial dysfunction in DM.
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. ssugiyam@kumamoto-u.ac.jp.|Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. ssugiyam@kumamoto-u.ac.jp.|Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 862-8556, Japan. ssugiyam@kumamoto-u.ac.jp.
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. hideaki@jinnouchi.or.jp.|Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. hideaki@jinnouchi.or.jp.|Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, 862-8556, Japan. hideaki@jinnouchi.or.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. hieshima@jinnouchi.or.jp.
authors.forename: Kunio
authors.initials: K
authors.lastname: Hieshima
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. kurinami@jinnouchi.or.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Kurinami
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. t-suzu@jinnouchi.or.jp.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. hisyo@jinnouchi.or.jp.
authors.forename: Fumio
authors.initials: F
authors.lastname: Miyamoto
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. dm-net@jinnouchi.or.jp.|Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. dm-net@jinnouchi.or.jp.
authors.forename: Keizo
authors.initials: K
authors.lastname: Kajiwara
authors.affiliation: Department of Community Medicine, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, 862-8556, Japan. kmatsui@kumamoto-u.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Matsui
authors.affiliation: Diabetes Care Center, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. tomio@jinnouchi.or.jp.|Diabetes Care Center, Cardiovascular Division, Jinnouchi Hospital, 6-2-3 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan. tomio@jinnouchi.or.jp.
authors.forename: Tomio
authors.initials: T
authors.lastname: Jinnouchi
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000069438:Ezetimibe / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D001786:Blood Glucose; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D000069438:Ezetimibe; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human