Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes

作者：Michael J. Haller, Desmond Schatz, Jay S. Skyler, Jeffrey P. Krischer, Brian N. Bundy, Jessica Miller, Mark A. Atkinson, Dorothy J. Becker, David A. Baidal, Linda A. DiMeglio, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Kevan C. Herold, Jennifer B. Marks, Antoinette Moran, Henry Rodriguez, William E. Russell, Darrell M. Wilson, Carla J. Greenbaum, Type 1 Diabetes TrialNet ATG-GCSF Study Group, Carla J. Greenbaum, Mark A. Atkinson, David A. Baidal, M. Battaglia, Dorothy Becker, P. J. Bingley, Emanuele Bosi, Jan C. Buckner, Mark A. Clements, Peter G. Colman, Linda A. DiMeglio, Carmella Evans‐Molina, Stephen E. Gitelman, Robin Goland, Peter A. Gottlieb, Kevan C. Herold, Mikael Knip, J. Krischer, Åke Lernmark, W. Moore, Antoinette Moran, Andrew J. Muir, J. Palmer, Mark Peakman, Louis H. Philipson, Philip Raskin, María J. Redondo, Henry Rodriguez, W. J. Russell, Lisa M. Spain, Desmond Schatz, Jay M. Sosenko, Diane K. Wherrett, Darrell M. Wilson, William E. Winter, Anette‐Gabriele Ziegler, Mark S. Anderson, Peter A. Antinozzi, Christophe Benoıst, J.J. Blum, Kasia Bourcier, Peter Chase, Michael Clare‐Salzler, Raphael Clynes, Catherine C. Cowie, George S. Eisenbarth, C. Garrison Fathman, Gilman D. Grave, L. Harrison, Bernhard J. Hering, Richard A. Insel, Sabine D. Jordan, Francine Kaufman, Tom Kay, Norma S. Kenyon, R. Klines, John M. Lachin, Ellen Leschek, Jeff Mahon, Jennifer B. Marks, Roshanak Monzavi, Kirsti Näntö‐Salonen, Gerald T. Nepom, Tihamer Orban, Robertson Parkman, Mark D. Pescovitz, John Peyman, A. Pugliese, John A. Ridge, Bart O. Roep, Maria Grazia Roncarolo, Peter J. Savage, Olli Simell, R S Sherwin, Mark Siegelman, Jay S. Skyler, Andrea K. Steck, James W. Thomas, Massimo Trucco, J. Richard Wagner, Katarzyna Bourcier, Carla J. Greenbaum, Jeffrey P. Krischer, Ellen Leschek, Lisa Rafkin, Lisa M. Spain, Catherine C. Cowie, Mary A. Foulkes, Richard A. Insel, Heidi Krause‐Steinrauf, John M. Lachin, Saúl Malozowski, John Peyman, J P Ridge, Peter J. Savage, Jay S. Skyler, Stephanie J. Zafonte, Carla J. Greenbaum, Lisa Rafkin, Jay M. Sosenko, Jay S. Skyler, Norma S. Kenyon, Irene Santiago, Jeffrey P. Krischer, Brian N. Bundy, Michael Abbondondolo, Timothy E. Adams, Darlene Amado, Ilma Asif, Matthew Boonstra, David Boulware, Brian N. Bundy, Cristina Burroughs, David Cuthbertson, Christopher Eberhard, Steve Fiske, Julie Ford, Jennifer Garmeson, Heather Guillette, Susan Geyer, Brian Hays, Courtney Henderson, Martha Henry, Kathleen Heyman, Belinda Hsiao, Christina Karges, Amanda Kinderman, Lindsay Lane, Ashley Leinbach, Shu Liu, Jennifer Lloyd, Jamie Malloy, Kristin Maddox, Julie Martin, Jessica Miller, Margaret Moore, Sarah Müller, Thuy Trang Nguyen, Ryan O’Donnell, Melissa M. Parker, M.J. Pereyra, Nichole Reed, A. Roberts, Kelly Sadler, Tina Stavros, Roy Tamura, Keith Wood, Ping Xu, Kenneth C. Young, Persida Alies, Franz Badias, Aaron Baker, Monica Bassi, Craig A. Beam, David Boulware, London Bounmananh, Susan Bream, Mary Deemer, Doug Freeman, Jessica Gough, Jinin Ginem, Moriah Granger, M C Holloway, Michelle Kieffer, Page Lane, Pat Law, Cristin Linton, Lavanya Nallamshetty, Vanessa Oduah, Yazandra Parrimon, Kate Paulus, Jennifer Pilger, Joy Ramiro, AQesha Luvon, Archana Ritzie, Audrey Sharma, Xiaohong Shor, Amanda Song, Jeanne Terry, M. W. Weinberger, Judith Wootten, Ellen Fradkin, Lisa Leschek, Catherine Spain, Saul Cowie, Peter Malozowski, G. Savage, Emily Beck, Rose Blumberg, Lori Gubitosi-Klug, Robert Laffel, Dennis Veatch, Jonathan Wallace, David Braun, Ake Brillon, B. Lernmark, Herman Hay Ming Lo, Ali Mitchell, Jorn Naji, Trevor Nerup, M.T. Orchard, Anastasios Steffes, Bernard Tsiatis, Brett Zinman, Lindsey Loechelt, Michael M. Baden, Adriana Green, Santica Weinberg, Jerry P. Marcovina, A. Allan Palmer, Liping Weinberg, William Yu, George S. Winter, Annie Eisenbarth, Emily L. Shultz, Kristin Batts, Mary Fitzpatrick, Randy Ramey, Christopher J. Guerra, Melita Webb, Carla Romasco, Sandra Greenbaum, Dana Lord, Wei VanBuecken, Marli Hao, D. K. McCulloch, Kim Hefty, R. Edward Varner, Ellen Goland, Sarah Greenberg, B POLLACK, L.B. Nelson, Linda Looper, Maria DiMeglio, Carmella Spall, Manasa Evans-Molina, Juan Mantravadi, Maureen Sanchez, Vanessa Mullen, Stephanie Patrick, Darrell M. Woerner, Tandy Wilson, Trudy Aye, Karen Esrey, Bonita Barahona, H.W. GORDON BAKER, C. Bitar, Martha Ghodrat, Stephen E. Hamilton, Christine T. Gitelman, Srinath Ferrara, Rebecca Sanda, Christine Wesch, Péter Török, Jordan Gottlieb, Carrie Lykens, A.B. Brill, Allison Michels, Michael J. Schauwecker, Desmond A. Haller, Mark A. Schatz, Laura M. Atkinson, Miriam Jacobsen, Todd M. Cintron, Clive H. Brusko, Clay E. Wasserfall, Jay S. Mathews, Jennifer M. Skyler, David Marks, Carlos Baidal, Della Blaschke, Antoinette Matheson, B. Moran, Anne Nathan, Janice Street, Beth Leschyshyn, Brittney Pappenfus, Nancy A. Nelson, Dorothy Flaherty, Kelly Becker, David Delallo, Karen Groscost, Henry Riley, Danielle Rodriguez, Emily Henson, William Eyth, Anne Russell, Faith L. Brown, Kevan Brendall, Herold, Laurie Feldman · 发表于：Diabetes Care · 年份：2018 · DOI：10.2337/dc18-0494 · 被引用次数：183 · 研究领域：Diabetes and associated disorders、Diabetes Management and Research、Pancreatic function and diabetes

OBJECTIVE A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration <100 days). RESEARCH DESIGN AND METHODS A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value < 0.025. RESULTS The 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively. CONCLUSIONS Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Futur...