title: Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes.
abstract: BACKGROUND
  Dipeptidyl peptidase 4 (DPP4) inhibitors are used for treatment of diabetes mellitus (DM). We hypothesized that sitagliptin, a DPP4-inhibitor, could improve endothelial dysfunction in DM patients with coronary artery disease (CAD).
  
  
  RESULTS
  The 40 patients with CAD and uncontrolled DM, aged 68.7±9.4 years (mean±standard deviation) (50% males, hemoglobin A1c [HbA1c] 7.4±1.0%) were assigned to either additional treatment with sitagliptin (50 mg/day, n=20) or aggressive conventional treatment (control, n=20) for 6 months. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry index (RHI). The clinical characteristics at baseline were not different between the groups. After treatment, fasting blood glucose and insulin levels, and lipid profiles were not different between the groups. HbA1c levels significantly improved similarly in both groups. The percent change in RHI was greater in the sitagliptin group than in the control group (62.4±59.2% vs. 15.9±22.0%, P<0.01). Furthermore, treatment with sitagliptin resulted in a significant decrease in the high-sensitivity C-reactive protein (hsCRP) level, but no such change was noted in the control group. Linear regression analysis demonstrated a significant negative relation between changes in RHI and hsCRP, but not between RHI and HbA1c.
  
  
  CONCLUSIONS
  Sitagliptin significantly improved endothelial function and inflammatory state in patients with CAD and uncontrolled DM, beyond its hypoglycemic action. These findings suggest that sitagliptin has beneficial effects on the cardiovascular system in DM patients.
authors: Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, and Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital, Kumamoto, Japan.
authors: Junichi
authors: J
authors: Matsubara
authors: Seigo
authors: S
authors: Sugiyama
authors: Eiichi
authors: E
authors: Akiyama
authors: Satomi
authors: S
authors: Iwashita
authors: Hirofumi
authors: H
authors: Kurokawa
authors: Keisuke
authors: K
authors: Ohba
authors: Hirofumi
authors: H
authors: Maeda
authors: Koichiro
authors: K
authors: Fujisue
authors: Eiichiro
authors: E
authors: Yamamoto
authors: Koichi
authors: K
authors: Kaikita
authors: Seiji
authors: S
authors: Hokimoto
authors: Hideaki
authors: H
authors: Jinnouchi
authors: Hisao
authors: H
authors: Ogawa
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008365:Manometry; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058729:Peripheral Arterial Disease / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D011719:Pyrazines / Q000627:therapeutic use*; D012307:Risk Factors; D000068900:Sitagliptin Phosphate; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D018836:Inflammation Mediators; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C517652:hemoglobin A1c protein, human