Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging

JACC Cardiovasc Imaging. 2013 Nov;6(11):1172-82. doi: 10.1016/j.jcmg.2013.09.004.

Abstract

Objectives: The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography.

Background: Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation.

Methods: Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio.

Results: Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031).

Conclusions: Our study indicated that pioglitazone attenuated left main trunk inflammation in patients with impaired glucose tolerance or DM in a glucose-lowering independent manner, suggesting that pioglitazone may protect against cardiac events in patients with impaired glucose tolerance or DM by suppressing coronary inflammation. (Anti-Inflammatory Effects of Pioglitazone; NCT00722631).

Keywords: (18)F-fluorodeoxyglucose; (18)F-fluorodeoxyglucose–positron emission tomography; CT; DM; FDG; FPG; HbA1c; IGT; IQR; LMT; PET; SUV; TBR; computed tomography; computed tomography angiography; coronary artery disease; diabetes mellitus; fasting plasma glucose; glycosylated hemoglobin; high-sensitivity C-reactive protein; hsCRP; impaired glucose tolerance; interquartile range; left main trunk; pioglitazone; positron emission tomography; standardized uptake value; target-to-background ratio; vascular inflammation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • C-Reactive Protein / metabolism
  • Coronary Angiography / methods*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / etiology
  • Coronary Vessels / diagnostic imaging
  • Coronary Vessels / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / diagnosis
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / etiology
  • Fluorodeoxyglucose F18*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Multimodal Imaging / methods*
  • Pioglitazone
  • Positron-Emission Tomography*
  • Predictive Value of Tests
  • Prospective Studies
  • Radiopharmaceuticals*
  • Sulfonylurea Compounds / therapeutic use
  • Thiazolidinediones / therapeutic use*
  • Time Factors
  • Tomography, X-Ray Computed*
  • Treatment Outcome

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Radiopharmaceuticals
  • Sulfonylurea Compounds
  • Thiazolidinediones
  • hemoglobin A1c protein, human
  • Fluorodeoxyglucose F18
  • glimepiride
  • C-Reactive Protein
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT00722631