Pioglitazone decreases coronary artery inflammation in impaired glucose tolerance and diabetes mellitus: evaluation by FDG-PET/CT imaging.
OBJECTIVE
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).
Department of Medicine, Division of Cardio-Vascular Medicine, Kurume University School of Medicine, Kurume, Japan.
Yoshikazu
Y
Nitta
Nobuhiro
N
Tahara
Atsuko
A
Tahara
Akihiro
A
Honda
Norihiro
N
Kodama
Minori
M
Mizoguchi
Hayato
H
Kaida
Masatoshi
M
Ishibashi
Naofumi
N
Hayabuchi
Hisao
H
Ikeda
Sho-ichi
S
Yamagishi
Tsutomu
T
Imaizumi
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D019788:Fluorodeoxyglucose F18; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; D002097:C-Reactive Protein; 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
(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