title: Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes.
abstract: BACKGROUND
  Exercise is recommended as a cornerstone of treatment for type 2 diabetes mellitus (T2DM), however, it is often poorly adopted by patients. Even in the absence of apparent cardiovascular disease, persons with T2DM have an impaired ability to carry out maximal and submaximal exercise and these impairments are correlated with cardiac and endothelial dysfunction. Glucagon-like pepetide-1 (GLP-1) augments endothelial and cardiac function in T2DM. We hypothesized that administration of a GLP-1 agonist (exenatide) would improve exercise capacity in T2DM.
  
  
  RESULTS
  Twenty-three participants (64±4years; mean±SE) with uncomplicated T2DM were randomized in a double-blinded manner to receive either 10μg BID of exenatide or matching placebo after baseline measurements. Treatment with exenatide did not improve VO2peak(P=0.1464) or VO2kinetics (P=0.2775). Diastolic function, assessed via resting lateral E:E', was improved with administration of exenatide compared with placebo (Placebo Pre: 7.6±1.0 vs. Post: 8.4±1.2 vs. Exenatide Pre: 8.1±0.7 vs. Post: 6.7±0.6; P=0.0127). Additionally, arterial stiffness measured by pulse wave velocity, was reduced with exenatide treatment compared with placebo (Placebo Pre: 10.5±0.8 vs. Post: 11.5±1.1s vs. Exenatide Pre: 11.4±1.8 vs. Post: 10.2±1.4s; P=0.0373). Exenatide treatment did not improve endothelial function (P=0.1793).
  
  
  CONCLUSIONS
  Administration of exenatide improved cardiac function and reduced arterial stiffness, however, these changes were not accompanied by improved functional exercise capacity. In order to realize the benefits of this drug on exercise capacity, combining exenatide with aerobic exercise training in participants with T2DM may be warranted.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Scalzo
authors.affiliation: Division of Geriatrics, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; Center for Women's Health Research, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; VAMC-Geriatric Research Education and Clinical Center (GRECC), Denver, Colorado 80215.
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: Moreau
authors.affiliation: Division of Geriatrics, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Cemal
authors.initials: C
authors.lastname: Ozemek
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Leah
authors.initials: L
authors.lastname: Herlache
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Shawna
authors.initials: S
authors.lastname: McMillin
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gilligan
authors.affiliation: Center for Women's Health Research, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Amy G
authors.initials: AG
authors.lastname: Huebschmann
authors.affiliation: Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Tim A
authors.initials: TA
authors.lastname: Bauer
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dorosz
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; Center for Women's Health Research, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; Veterans Administration Medical Center (VAMC), Denver, Colorado 80215.
authors.forename: Jane E B
authors.initials: JE
authors.lastname: Reusch
authors.affiliation: Center for Women's Health Research, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215; Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine (UCSOM), Denver, Colorado 80215. Electronic address: judy.regensteiner@ucdenver.edu.
authors.forename: Judith G
authors.initials: JG
authors.lastname: Regensteiner
mesh_terms: D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D058065:Diabetic Cardiomyopathies / Q000517:prevention & control*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D000077270:Exenatide; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D063177:Pulse Wave Analysis; D057185:Sedentary Behavior; D059289:Vascular Stiffness / Q000187:drug effects*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000517:prevention & control*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
keywords: Cardiovascular diseases; Diabetes mellitus; Exercise; GLP-1; VO(2)peak