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Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET/CT imaging study of carotid artery and ascending aorta.

AbstractOBJECTIVES:
The aim of this study was to compare the effect of pioglitazone, an insulin sensitizer, with glimepiride, an insulin secretagogue, on atherosclerotic plaque inflammation by using serial (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging.
BACKGROUND:
Atherosclerosis is intrinsically an inflammatory disease. Although hyperglycemia is associated with an increased risk of atherosclerotic cardiovascular disease, there are no clinical data to show the preference of any specific oral hypoglycemic agents to prevent atherosclerotic plaque inflammation.
METHODS:
A total of 56 impaired glucose tolerant or diabetic patients with carotid atherosclerosis underwent a complete history, determinations of blood chemistries, anthropometric variables, and FDG-PET. They were randomly assigned to receive either pioglitazone (15 to 30 mg) or glimepiride (0.5 to 4.0 mg) for 4 months with titration to optimal dosage. Effects of the drugs on atherosclerotic plaque inflammation were evaluated by FDG-PET at study completion. Plaque inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio.
RESULTS:
The study was completed in 31 pioglitazone-treated patients and 21 glimepiride-treated patients. Although both treatments reduced fasting plasma glucose and hemoglobin A1c values comparably, pioglitazone, but not glimepiride, decreased atherosclerotic plaque inflammation. Compared with glimepiride, pioglitazone significantly increased high-density lipoprotein cholesterol level. High-sensitivity C-reactive protein was decreased by pioglitazone, whereas it was increased by glimepiride. Multiple stepwise regression analysis revealed that the increase in high-density lipoprotein cholesterol level was independently associated with the attenuation of plaque inflammation.
CONCLUSIONS:
Our present study suggests that pioglitazone could attenuate atherosclerotic plaque inflammation in patients with impaired glucose tolerance or in diabetic patients independent of glucose lowering effect. Pioglitazone may be a promising strategy for the treatment of atherosclerotic plaque inflammation in impaired glucose tolerance or diabetic patients. (Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT; NCT00722631).
AuthorsMinori Mizoguchi, Nobuhiro Tahara, Atsuko Tahara, Yoshikazu Nitta, Norihiro Kodama, Toyoharu Oba, Kazutoshi Mawatari, Hideo Yasukawa, Hayato Kaida, Masatoshi Ishibashi, Naofumi Hayabuchi, Haruhito Harada, Hisao Ikeda, Sho-Ichi Yamagishi, Tsutomu Imaizumi
JournalJACC. Cardiovascular imaging (JACC Cardiovasc Imaging) Vol. 4 Issue 10 Pg. 1110-8 (Oct 2011) ISSN: 1876-7591 [Electronic] United States
PMID21999871 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)
CopyrightCopyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents
  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Radiopharmaceuticals
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Fluorodeoxyglucose F18
  • glimepiride
  • C-Reactive Protein
  • Pioglitazone
Topics
  • Aged
  • Anti-Inflammatory Agents (therapeutic use)
  • Aortic Diseases (diagnostic imaging, drug therapy, etiology)
  • Aortography
  • Biomarkers (blood)
  • Blood Glucose (drug effects, metabolism)
  • C-Reactive Protein (metabolism)
  • Carotid Artery Diseases (diagnostic imaging, drug therapy, etiology)
  • Cholesterol, HDL (blood)
  • Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
  • Diabetic Angiopathies (diagnostic imaging, drug therapy, etiology)
  • Female
  • Fluorodeoxyglucose F18
  • Glucose Intolerance (blood, complications, drug therapy)
  • Glycated Hemoglobin (metabolism)
  • Humans
  • Hypoglycemic Agents (therapeutic use)
  • Inflammation (diagnostic imaging, drug therapy, etiology)
  • Japan
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Pioglitazone
  • Positron-Emission Tomography
  • Predictive Value of Tests
  • Prospective Studies
  • Radiopharmaceuticals
  • Regression Analysis
  • Sulfonylurea Compounds (therapeutic use)
  • Thiazolidinediones (therapeutic use)
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome

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