PMID- 26253538 OWN - NLM STAT- MEDLINE DCOM- 20160421 LR - 20181113 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 14 DP - 2015 Aug 8 TI - Glucagon-like peptide-1 protects against ischemic left ventricular dysfunction during hyperglycemia in patients with coronary artery disease and type 2 diabetes mellitus. PG - 102 LID - 10.1186/s12933-015-0259-3 [doi] LID - 102 AB - BACKGROUND: Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM). METHODS: In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments. RESULTS: In study 1, the HHC (compared with control) increased glucose (13.0 +/- 1.9 versus 4.8 +/- 0.5 mmol/l, p < 0.0001) and insulin (1,212 +/- 514 versus 114 +/- 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 +/- 175 versus 1,001 +/- 333 mumol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 +/- 5.0 versus 71.3 +/- 4.3%, p = 0.004) and regional (peak systolic strain -18.1 +/- 6.6 versus -15.5 +/- 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. CONCLUSIONS: In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM. TRIAL REGISTRATION: http://www.isrctn.org . Unique identifier ISRCTN69686930. FAU - McCormick, Liam M AU - McCormick LM AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. drliammccormick@doctors.org.uk. FAU - Heck, Patrick M AU - Heck PM AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. pmheck@doctors.org.uk. FAU - Ring, Liam S AU - Ring LS AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. liamring@doctors.org.uk. FAU - Kydd, Anna C AU - Kydd AC AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. annakydd@doctors.org.uk. FAU - Clarke, Sophie J AU - Clarke SJ AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. sophie.j.clarke@gmail.com. FAU - Hoole, Stephen P AU - Hoole SP AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. stevieh@doctors.org.uk. FAU - Dutka, David P AU - Dutka DP AD - Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. dpd24@medschl.cam.ac.uk. AD - Department of Cardiovascular Medicine, ACCI Level 6, Addenbrooke's Hospital, Box 110, Hills Rd, Cambridge, CB2 0QQ, UK. dpd24@medschl.cam.ac.uk. LA - eng GR - Medical Research Council/United Kingdom PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150808 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Insulin) RN - 0 (Peptide Fragments) RN - 119637-73-9 (glucagon-like peptide 1 (7-36)amide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Aged MH - Biomarkers/blood MH - Biomechanical Phenomena MH - Blood Glucose/*drug effects/metabolism MH - Coronary Artery Disease/*complications/diagnosis MH - Diabetes Mellitus, Type 2/blood/*complications/diagnosis MH - Diabetic Cardiomyopathies/diagnosis/etiology/physiopathology/*prevention & control MH - Echocardiography, Doppler, Color MH - Echocardiography, Stress MH - Female MH - Glucagon-Like Peptide 1/*administration & dosage MH - Glucose Clamp Technique MH - Humans MH - Hyperglycemia/blood/*complications/diagnosis MH - Incretins/*administration & dosage MH - Infusions, Intravenous MH - Insulin/blood MH - Male MH - Middle Aged MH - Myocardial Contraction/drug effects MH - Peptide Fragments/*administration & dosage MH - Stroke Volume/drug effects MH - Ventricular Dysfunction, Left/diagnosis/etiology/physiopathology/*prevention & control MH - Ventricular Function, Left/*drug effects PMC - PMC4528379 EDAT- 2015/08/09 06:00 MHDA- 2016/04/22 06:00 PMCR- 2015/08/08 CRDT- 2015/08/09 06:00 PHST- 2015/05/16 00:00 [received] PHST- 2015/07/17 00:00 [accepted] PHST- 2015/08/09 06:00 [entrez] PHST- 2015/08/09 06:00 [pubmed] PHST- 2016/04/22 06:00 [medline] PHST- 2015/08/08 00:00 [pmc-release] AID - 10.1186/s12933-015-0259-3 [pii] AID - 259 [pii] AID - 10.1186/s12933-015-0259-3 [doi] PST - epublish SO - Cardiovasc Diabetol. 2015 Aug 8;14:102. doi: 10.1186/s12933-015-0259-3.