Document Detail


DPP-4 inhibition by sitagliptin improves the myocardial response to dobutamine stress and mitigates stunning in a pilot study of patients with coronary artery disease.
MedLine Citation:
PMID:  20075143     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted postprandially that promotes myocardial glucose uptake. The active amide GLP-1 (7-36) is degraded by the enzyme DPP-4, and drugs that inhibit this enzyme (such as sitagliptin) have been introduced to treat type 2 diabetes. We assessed the hypothesis that increasing the plasma concentration of GLP-1 by DPP-4 inhibition would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography in patients with coronary artery disease.
METHODS AND RESULTS: Fourteen patients with coronary artery disease and preserved LV function awaiting revascularization were studied. After either a single dose of 100 mg sitagliptin or placebo, 75 g of glucose was given orally to promote GLP-1 secretion and dobutamine stress echocardiography was conducted with tissue Doppler imaging at rest, peak stress, and 30 minutes. After sitagliptin, plasma GLP-1 (7-36) was increased at peak stress (16.5+/-10.7 versus 9.7+/-8.7 pg/mL; P=0.003) and in recovery (12.4+/-5.5 versus 9.0+/-5.5 pg/mL; P=0.01), and the LV response to stress was enhanced (ejection fraction, 72.6+/-7.2 versus 63.9+/-7.9%, P=0.0001; mitral annular systolic velocity, 12.54+/-3.18 versus 11.49+/-2.52 cm/s; P=0.0006). DPP-4 inhibition also improved LV regional function in the 12 paired nonapical segments assessed by peak systolic tissue Doppler (velocity, 10.56+/-4.49 versus 9.81+/-4.26 cm/s, P=0.002; strain, -15.9+/-6.3 versus -14.6+/-6.6%, P=0.01; strain rate, -2.04+/-1.04 versus -1.75+/-0.98 s(-1), P=0.0003). This was predominantly due to a cardioprotective effect on ischemic segments (velocity in ischemic segments, 9.77+/-4.18 versus 8.74+/-3.87, P=0.007; velocity in nonischemic segments, 11.51+/-4.70 versus 11.14+/-4.38, P=0.14). In recovery, sitagliptin attenuated the postischemic stunning seen after the control study.
CONCLUSIONS: The augmentation of GLP-1 (7-36) by inhibition of DPP-4 improves global and regional LV performance in response to stress and mitigates postischemic stunning in humans with coronary artery disease. Clinical Trial Registration- URL: http://www.isrctn.org. Unique identifier: ISRCTN78649100.
Authors:
Philip A Read; Fakhar Z Khan; Patrick M Heck; Stephen P Hoole; David P Dutka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-14
Journal Detail:
Title:  Circulation. Cardiovascular imaging     Volume:  3     ISSN:  1942-0080     ISO Abbreviation:  Circ Cardiovasc Imaging     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-17     Completed Date:  2010-05-07     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  101479935     Medline TA:  Circ Cardiovasc Imaging     Country:  United States    
Other Details:
Languages:  eng     Pagination:  195-201     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ISRCTN/ISRCTN78649100
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MeSH Terms
Descriptor/Qualifier:
Coronary Artery Disease / physiopathology*,  ultrasonography*
Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
Echocardiography, Stress*
Female
Glucagon-Like Peptide 1 / blood*
Humans
Male
Middle Aged
Myocardial Stunning / prevention & control*
Pilot Projects
Pyrazines / therapeutic use*
Reproducibility of Results
Triazoles / therapeutic use*
Ventricular Dysfunction, Left / prevention & control*,  ultrasonography*
Grant Support
ID/Acronym/Agency:
G0701720//Medical Research Council
Chemical
Reg. No./Substance:
0/Dipeptidyl-Peptidase IV Inhibitors; 0/Pyrazines; 0/Triazoles; 89750-14-1/Glucagon-Like Peptide 1; QFP0P1DV7Z/sitagliptin

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