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418 Activation of the Glucagon-Like Peptide-1 Pathway in Obese Pre-Diabetic Individuals Improves Endothelial Function Independently of Weight Loss
- Mona Mashayekhi, Joshua A. Beckman, Erica M. Garner, Hui Nian, Chang Yu, Sara E. Howard, Bradley Perkins, Jessica K. Devin, John R. Koethe, Jonathan D. Brown, Heidi Silver, James M. Luther, Nancy J. Brown
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, pp. 81-82
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OBJECTIVES/GOALS: We aimed to determine if GLP-1 receptor agonists exert beneficial effects on surrogate measures of cardiovascular function independently of weight loss. Our objective was to compare the outcomes between GLP-1 receptor agonist treatment versus a similar drug without cardiovascular benefit versus weight loss through diet alone. METHODS/STUDY POPULATION: We enrolled 88 individuals with obesity (BMI ≥ 30kg/m2) and pre-diabetes and randomized them in a 2:1:1 ratio to 14 weeks of the GLP-1 receptor agonist liraglutide, the dipeptidyl peptidase-4 inhibitor sitagliptin, or hypocaloric diet. Sitagliptin blocks degradation of endogenous GLP-1 but does not cause weight loss or lower adverse cardiovascular outcomes. Treatment was double-blinded and placebo-controlled for drug, and unblinded for diet. Primary endpoints were flow-mediated dilation (FMD) to assess endothelial vasodilatory function, and plasminogen activator inhibitor-1 (PAI-1) to assess endothelial fibrinolytic function. We used a general linear model for each outcome and included gender as a covariate for FMD. Baseline characteristics were similar. Mean age was 50, with 32% men and 13% black. RESULTS/ANTICIPATED RESULTS: At 14 weeks, diet and liraglutide caused weight loss (diet -4.3 ± 3.2 kg, P<0.01; liraglutide -2.7 ± 3.2, P<0.01), while sitagliptin did not (-0.7 ± 2.0, P=0.17). Diet did not improve FMD at 14 weeks compared to baseline (+0.9%, 95% CI [-1.5, 3.3], P=0.46). FMD tended to increase after liraglutide and sitagliptin but was not significant (liraglutide +1.2 [-0.3, 2.8], P=0.12; sitagliptin +1.6 [-0.6, 3.8], P=0.15). Given that liraglutide and sitagliptin work through the same GLP-1 pathway, we combined the liraglutide and sitagliptin groups for overall effect on FMD, which was significantly improved from baseline (+1.4 [0.1, 2.8], P=0.04). Diet and liraglutide improved PAI-1 at 14 weeks (diet -4.4U/mL, [-8.5, -0.2], P=0.04; liraglutide -3.4 [-6.0, -0.7], P=0.01), while sitagliptin did not (-1.4 [-5.1, 2.3], P=0.46). DISCUSSION/SIGNIFICANCE: Activation of the GLP-1 pathway by liraglutide or sitagliptin improves FMD independent of weight loss, while PAI-1 improvement is weight-loss dependent and is only seen after liraglutide or diet. Our study suggests the cardiovascular benefit of liraglutide may be due to combined improvements in endothelial vasodilatory and fibrinolytic function.
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- By Tod C. Aeby, Melanie D. Altizer, Ronan A. Bakker, Meghann E. Batten, Anita K. Blanchard, Brian Bond, Megan A. Brady, Saweda A. Bright, Ellen L. Brock, Amy Brown, Ashley Carroll, Jori S. Carter, Frances Casey, Weldon Chafe, David Chelmow, Jessica M. Ciaburri, Stephen A. Cohen, Adrianne M. Colton, PonJola Coney, Jennifer A. Cross, Julie Zemaitis DeCesare, Layson L. Denney, Megan L. Evans, Nicole S. Fanning, Tanaz R. Ferzandi, Katie P. Friday, Nancy D. Gaba, Rajiv B. Gala, Andrew Galffy, Adrienne L. Gentry, Edward J. Gill, Philippe Girerd, Meredith Gray, Amy Hempel, Audra Jolyn Hill, Chris J. Hong, Kathryn A. Houston, Patricia S. Huguelet, Warner K. Huh, Jordan Hylton, Christine R. Isaacs, Alison F. Jacoby, Isaiah M. Johnson, Nicole W. Karjane, Emily E. Landers, Susan M. Lanni, Eduardo Lara-Torre, Lee A. Learman, Nikola Alexander Letham, Rachel K. Love, Richard Scott Lucidi, Elisabeth McGaw, Kimberly Woods McMorrow, Christopher A. Manipula, Kirk J. Matthews, Michelle Meglin, Megan Metcalf, Sarah H. Milton, Gaby Moawad, Christopher Morosky, Lindsay H. Morrell, Elizabeth L. Munter, Erin L. Murata, Amanda B. Murchison, Nguyet A. Nguyen, Nan G. O’Connell, Tony Ogburn, K. Nathan Parthasarathy, Thomas C. Peng, Ashley Peterson, Sarah Peterson, John G. Pierce, Amber Price, Heidi J. Purcell, Ronald M. Ramus, Nicole Calloway Rankins, Fidelma B. Rigby, Amanda H. Ritter, Barbara L. Robinson, Danielle Roncari, Lisa Rubinsak, Jennifer Salcedo, Mary T. Sale, Peter F. Schnatz, John W. Seeds, Kathryn Shaia, Karen Shelton, Megan M. Shine, Haller J. Smith, Roger P. Smith, Nancy A. Sokkary, Reni A. Soon, Aparna Sridhar, Lilja Stefansson, Laurie S. Swaim, Chemen M. Tate, Hong-Thao Thieu, Meredith S. Thomas, L. Chesney Thompson, Tiffany Tonismae, Angela M. Tran, Breanna Walker, Alan G. Waxman, C. Nathan Webb, Valerie L. Williams, Sarah B. Wilson, Elizabeth M. Yoselevsky, Amy E. Young
- Edited by David Chelmow, Virginia Commonwealth University, Christine R. Isaacs, Virginia Commonwealth University, Ashley Carroll, Virginia Commonwealth University
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- Book:
- Acute Care and Emergency Gynecology
- Published online:
- 05 November 2014
- Print publication:
- 30 October 2014, pp ix-xiv
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- By Lenard A. Adler, Pinky Agarwal, Rehan Ahmed, Jagga Rao Alluri, Fawaz Al-Mufti, Samuel Alperin, Michael Amoashiy, Michael Andary, David J. Anschel, Padmaja Aradhya, Vandana Aspen, Esther Baldinger, Jee Bang, George D. Baquis, John J. Barry, Jason J. S. Barton, Julius Bazan, Amanda R. Bedford, Marlene Behrmann, Lourdes Bello-Espinosa, Ajay Berdia, Alan R. Berger, Mark Beyer, Don C. Bienfang, Kevin M. Biglan, Thomas M. Boes, Paul W. Brazis, Jonathan L. Brisman, Jeffrey A. Brown, Scott E. Brown, Ryan R. Byrne, Rina Caprarella, Casey A. Chamberlain, Wan-Tsu W. Chang, Grace M. Charles, Jasvinder Chawla, David Clark, Todd J. Cohen, Joe Colombo, Howard Crystal, Vladimir Dadashev, Sarita B. Dave, Jean Robert Desrouleaux, Richard L. Doty, Robert Duarte, Jeffrey S. Durmer, Christyn M. Edmundson, Eric R. Eggenberger, Steven Ender, Noam Epstein, Alberto J. Espay, Alan B. Ettinger, Niloofar (Nelly) Faghani, Amtul Farheen, Edward Firouztale, Rod Foroozan, Anne L. Foundas, David Elliot Friedman, Deborah I. Friedman, Steven J. Frucht, Oded Gerber, Tal Gilboa, Martin Gizzi, Teneille G. Gofton, Louis J. Goodrich, Malcolm H. Gottesman, Varda Gross-Tsur, Deepak Grover, David A. Gudis, John J. Halperin, Maxim D. Hammer, Andrew R. Harrison, L. Anne Hayman, Galen V. Henderson, Steven Herskovitz, Caitlin Hoffman, Laryssa A. Huryn, Andres M. Kanner, Gary P. Kaplan, Bashar Katirji, Kenneth R. Kaufman, Annie Killoran, Nina Kirz, Gad E. Klein, Danielle G. Koby, Christopher P. Kogut, W. Curt LaFrance, Patrick J.M. Lavin, Susan W. Law, James L. Levenson, Richard B. Lipton, Glenn Lopate, Daniel J. Luciano, Reema Maindiratta, Robert M. Mallery, Georgios Manousakis, Alan Mazurek, Luis J. Mejico, Dragana Micic, Ali Mokhtarzadeh, Walter J. Molofsky, Heather E. Moss, Mark L. Moster, Manpreet Multani, Siddhartha Nadkarni, George C. Newman, Rolla Nuoman, Paul A. Nyquist, Gaia Donata Oggioni, Odi Oguh, Denis Ostrovskiy, Kristina Y. Pao, Juwen Park, Anastas F. Pass, Victoria S. Pelak, Jeffrey Peterson, John Pile-Spellman, Misha L. Pless, Gregory M. Pontone, Aparna M. Prabhu, Michael T. Pulley, Philip Ragone, Prajwal Rajappa, Venkat Ramani, Sindhu Ramchandren, Ritesh A. Ramdhani, Ramses Ribot, Heidi D. Riney, Diana Rojas-Soto, Michael Ronthal, Daniel M. Rosenbaum, David B. Rosenfield, Durga Roy, Michael J. Ruckenstein, Max C. Rudansky, Eva Sahay, Friedhelm Sandbrink, Jade S. Schiffman, Angela Scicutella, Maroun T. Semaan, Robert C. Sergott, Aashit K. Shah, David M. Shaw, Amit M. Shelat, Claire A. Sheldon, Anant M. Shenoy, Yelizaveta Sher, Jessica A. Shields, Tanya Simuni, Rajpaul Singh, Eric E. Smouha, David Solomon, Mehri Songhorian, Steven A. Sparr, Egilius L. H. Spierings, Eve G. Spratt, Beth Stein, S.H. Subramony, Rosa Ana Tang, Cara Tannenbaum, Hakan Tekeli, Amanda J. Thompson, Michael J. Thorpy, Matthew J. Thurtell, Pedro J. Torrico, Ira M. Turner, Scott Uretsky, Ruth H. Walker, Deborah M. Weisbrot, Michael A. Williams, Jacques Winter, Randall J. Wright, Jay Elliot Yasen, Shicong Ye, G. Bryan Young, Huiying Yu, Ryan J. Zehnder
- Edited by Alan B. Ettinger, Albert Einstein College of Medicine, New York, Deborah M. Weisbrot, State University of New York, Stony Brook
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- Book:
- Neurologic Differential Diagnosis
- Published online:
- 05 June 2014
- Print publication:
- 17 April 2014, pp xi-xx
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- By Joanne R. Adler, David A. Alexander, Laurence Alison, Catherine C. Ayoub, Peter Banister, Anthony R. Beech, Amanda Biggs, Julian Boon, Adrian Bowers, Neil Brewer, Eric Broekaert, Paula Brough, Jennifer M. Brown, Kevin Browne, Elizabeth A. Campbell, David Canter, Michael Carlin, Shihning Chou, Martin A. Conway, Claire Cooke, David Cooke, Ilse Derluyn, Robert J. Edelmann, Vincent Egan, Tom Ellis, Marie Eyre, David P. Farrington, Seena Fazel, Daniel B. Fishman, Victoria Follette, Katarina Fritzon, Elizabeth Gilchrist, Nathan D. Gillard, Renée Gobeil, Agnieszka Golec de Zavala, Jane Goodman-Delahunty, Lynsey Gozna, Don Grubin, Gisli H. Gudjonsson, Helinä Häkkänen-Nyholm, Guy Hall, Nathan Hall, Roisin Hall, Sean Hammond, Leigh Harkins, Grant T. Harris, Camilla Herbert, Robert D. Hoge, Todd E. Hogue, Clive R. Hollin, Lorraine Hope, Miranda A. H. Horvath, Kevin Howells, Carol A. Ireland, Jane L. Ireland, Mark Kebbell, Michael King, Bruce D. Kirkcaldy, Heidi La Bash, Cara Laney, William R. Lindsay, Elizabeth F. Loftus, L. E. Marshall, W. L. Marshall, James McGuire, Neil McKeganey, T. M. McMillan, Mary McMurran, Joav Merrick, Becky Milne, Joanne M. Nadkarni, Claire Nee, M. D. O’Brien, William O’Donohue, Darragh O’Neill, Jane Palmer, Adria Pearson, Derek Perkins, Devon L. L. Polaschek, Louise E. Porter, Charlotte C. Powell, Graham E. Powell, Martine Powell, Christine Puckering, Ethel Quayle, Vernon L. Quinsey, Marnie E. Rice, Randall Richardson-Vejlgaard, Richard Rogers, Louis B Schlesinger, Carolyn Semmler, G. A. Serran, Ralph C. Serin, John L. Taylor, Max Taylor, Brian Thomas-Peter, Paul A. Tiffin, Graham Towl, Rosie Travers, Arlene Vetere, Graham Wagstaff, Helen Wakeling, Fiona Warren, Brandon C. Welsh, David Wexler, Margaret Wilson, Dan Yarmey, Susan Young
- Edited by Jennifer M. Brown, London School of Economics and Political Science, Elizabeth A. Campbell, University of Glasgow
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- Book:
- The Cambridge Handbook of Forensic Psychology
- Published online:
- 06 July 2010
- Print publication:
- 29 April 2010, pp xix-xxiii
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Chemical-Biological-Radiological-Nuclear (CBRN) Analytical Framework Based upon the “Guidelines for Emergency Response in the Utstein Style”, Developed by the World Association of Disaster and Emergency Medicine
- D. D. Schnelle, Lynn Difato, Commander Richard Guzman, Brian E. Jones, Michael Gately, Craig Cullen, Heidi E. Brown, Lara Feldhausen
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- Journal:
- Prehospital and Disaster Medicine / Volume 17 / Issue S2 / December 2002
- Published online by Cambridge University Press:
- 11 April 2022, p. S3
- Print publication:
- December 2002
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