Chronic Dipeptidyl Peptidase-4 Inhibition With Sitagliptin Is Associated With Sustained Protection Against Ischemic Left Ventricular Dysfunction in a Pilot Study of Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease
| Autor: | Philip A. Read, Simon Bond, Liam Ring, Stephen P. Hoole, David P. Dutka, Anna C. Kydd, Liam M. McCormick |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Dipeptidyl Peptidase 4 Heart Ventricles Myocardial Ischemia Ischemia Pilot Projects Coronary Artery Disease Coronary Angiography Coronary artery disease Electrocardiography Ventricular Dysfunction Left Glucagon-Like Peptide 1 Internal medicine Diabetes mellitus medicine Humans Radiology Nuclear Medicine and imaging Dipeptidyl peptidase-4 Aged Dipeptidyl-Peptidase IV Inhibitors Ejection fraction business.industry Sitagliptin Phosphate Type 2 Diabetes Mellitus Stroke Volume Triazoles medicine.disease Glucagon-like peptide-1 Echocardiography Doppler Treatment Outcome Diabetes Mellitus Type 2 Pyrazines Sitagliptin Cardiology Female Cardiology and Cardiovascular Medicine business Echocardiography Stress Follow-Up Studies medicine.drug |
| Zdroj: | Circulation: Cardiovascular Imaging. 7:274-281 |
| ISSN: | 1942-0080 1941-9651 |
| DOI: | 10.1161/circimaging.113.000785 |
| Popis: | Background— The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7–36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease. Methods and Results— A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-1 (7–36) levels and, at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%; P P =0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, −2.27±0.65 versus −1.98±0.58 s −1 ; P =0.001), whereas no effect was seen in nonischemic segments (−2.19±0.48 versus −2.18±0.54 s −1 ; P =0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan. Conclusions— The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning. Clinical Trial Registration— URL: http://www.isrctn.org . Unique identifier ISRCTN61646154. |
| Databáze: | OpenAIRE |
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