title: 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.
abstract: OBJECTIVE
  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).
authors: Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Minori
authors: M
authors: Mizoguchi
authors: Nobuhiro
authors: N
authors: Tahara
authors: Atsuko
authors: A
authors: Tahara
authors: Yoshikazu
authors: Y
authors: Nitta
authors: Norihiro
authors: N
authors: Kodama
authors: Toyoharu
authors: T
authors: Oba
authors: Kazutoshi
authors: K
authors: Mawatari
authors: Hideo
authors: H
authors: Yasukawa
authors: Hayato
authors: H
authors: Kaida
authors: Masatoshi
authors: M
authors: Ishibashi
authors: Naofumi
authors: N
authors: Hayabuchi
authors: Haruhito
authors: H
authors: Harada
authors: Hisao
authors: H
authors: Ikeda
authors: Sho-Ichi
authors: S
authors: Yamagishi
authors: Tsutomu
authors: T
authors: Imaizumi
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D001027:Aortography; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D007564:Japan; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D012044:Regression Analysis; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D019788:Fluorodeoxyglucose F18; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D019275:Radiopharmaceuticals; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C057619:glimepiride