Diabetes
American Diabetes Association
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Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data
Michael J. Haller S. Alice Long J. Lori Blanchfield Desmond A. Schatz Jay S. Skyler Jeffrey P. Krischer Brian N. Bundy Susan M. Geyer Megan V. Warnock Jessica L. 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 Carla J. Greenbaum Mark A. Atkinson David A. Baidal Manuela Battaglia Dorothy Becker Penelope Bingley Emanuele Bosi Jane Buckner Mark Clements Peter G. Colman Linda DiMeglio Carmella Evans-Molina Stephen E. Gitelman Robin Goland Peter Gottlieb Kevan Herold Mikael Knip Jeffrey P. Krischer Ake Lernmark Wayne Moore Antoinette Moran Andrew Muir Jerry Palmer Mark Peakman Louis Philipson Philip Raskin Maria Redondo Henry Rodriguez William Russell Desmond A. Schatz Jay M. Sosenko Lisa Spain John Wentworth Diane Wherrett Darrell M. Wilson William Winter Anette Ziegler Mark Anderson Peter Antinozzi Richard Insel Thomas Kay Jennifer B. Marks Alberto Pugliese Bart Roep Jay S. Skyler Jorma Toppari Carla J. Greenbaum Jeffrey P. Krischer Ellen Leschek Lisa Spain Katarzyna Bourcier Richard Insel John Ridge Jay S. Skyler Carla J. Greenbaum Lisa Rafkin Jay M. Sosenko Jay S. Skyler Irene Santiago Jeffrey P. Krischer Brian Bundy Michael Abbondondolo Timothy Adams Ilma Asif Jenna Bjellquist Matthew Boonstra Cristina Burroughs Mario Cleves David Cuthbertson Meagan DeSalvatore Christopher Eberhard Steve Fiske Julie Ford Jennifer Garmeson Susan Geyer Brian Hays Courtney Henderson Martha Henry Kathleen Heyman Belinda Hsiao Christina Karges Beata-Gabriela Koziol Lindsay Lane Shu Liu Jennifer Lloyd Kristin Maddox Jamie Malloy Julie Martin Cameron McNeill Margaret Moore Sarah Muller Thuy Nguyen Jodie Nunez Ryan O’Donnell Melissa Parker M.J. Pereyra Amy Roberts Kelly Sadler Christine Sullivan Roy Tamura Elon Walker-Veras Megan V. Warnock Keith Wood Rebecca Wood Ping Xu Vanessa Yanek Kenneth Young Darlene Amado Amanda Kinderman Ashley Leinbach Jessica Miller Nichole Reed Tina Stavros Ellen Leschek Lisa Spain Emily Blumberg Sean Aas Gerald Beck Rose Gubitosi-Klug Lori Laffel Robert Vigersky Dennis Wallace David Brillon Robert Veatch Brett Loechelt Lindsey Baden Peter Gottlieb Michael Green Ellen Leschek Adriana Weinberg Santica Marcovina Jerry P. Palmer Jay Tischfield Adriana Weinberg William Winter Liping Yu Annie Shultz Emily Batts Arielle Pagryzinski Mary Ramey Meghan Tobin Kristin Fitzpatrick Randy Guerra Melita Romasco Christopher Webb Peter Gottlieb Maya Barr Mary Drye Jordan Lykens Aaron Michels Allison Schauwecker Andrea Steck Paul Wadwa Carla J. Greenbaum Jane Buckner Wei Hao Sandra Lord Marli McCulloch-Olson Mary Ramey Elaine Sachter Jenna Snavely Meghan Tobin Corinna Tordillos Dana VanBuecken Robin Goland Analia Alvarez Magdalena Bogun Rachelle Gandica Natasha Leibel Sarah Pollak Barney Softness Kristen Williams Bryce Nelson James Amrhein Lisa Looper Elaine Moreland Andrew Smith Beth Weir Lori Wise Linda DiMeglio Carmella Evans-Molina Manasa Mantravadi Maureen Mullen Vanessa Patrick Maria Spall Stephanie Woerner Darrell M. Wilson Nora Arrizon-Ruiz Tandy Aye Laura Bachrach Karen Barahona Trudy Esrey Laura Nally Stephen E. Gitelman Mark Anderson Glenna Auerback Jeanne Buchanan Christine T. Ferrara Karen Ko Srinath Sanda Christine Torok Rebecca Wesch Michael J. Haller Anastasia Albanese-O'Neill Todd Brusko Miriam Cintron Jennifer Hosford Laura M. Jacobsen Henry Rohrs Desmond A. Schatz Janet Silverstein Paula Towe David A. Baidal Carlos Blaschke Della Matheson Janine Sanchez Natalia Sanders-Branca Jay S. Skyler Jay M. Sosenko Antoinette Moran Janice Leschyshyn Jennifer McVean Brandon Nathan Brittney Nelson Beth Pappenfus Jessica Ruedy Anne Street Muna Sunni Darcy Weingartner Dorothy Becker Kelli DeLallo Ana Diaz David Groscost Mary Beth Klein Ingrid Libman Karen Riley Henry Rodriguez Sureka Bollepalli Rachel Brownstein Emily Eyth Danielle Henson Michele Laine Dorothy Shulman William Russell Faith Brendle Anne Brown Brenna Dixon Justin Gregory Dan Moore James Thomas Kevan Herold Laurie Feldman William Tamborlane
Volume: 68, Issue: 6
DOI 10.2337/db19-0057
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Abstract

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test–stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.

https://www.researchpad.co/tools/openurl?pubtype=article&doi=10.2337/db19-0057&title=Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA<sub>1c</sub>, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data&author=Michael J. Haller,S. Alice Long,J. Lori Blanchfield,Desmond A. Schatz,Jay S. Skyler,Jeffrey P. Krischer,Brian N. Bundy,Susan M. Geyer,Megan V. Warnock,Jessica L. 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,Carla J. Greenbaum,Mark A. Atkinson,David A. Baidal,Manuela Battaglia,Dorothy Becker,Penelope Bingley,Emanuele Bosi,Jane Buckner,Mark Clements,Peter G. Colman,Linda DiMeglio,Carmella Evans-Molina,Stephen E. Gitelman,Robin Goland,Peter Gottlieb,Kevan Herold,Mikael Knip,Jeffrey P. Krischer,Ake Lernmark,Wayne Moore,Antoinette Moran,Andrew Muir,Jerry Palmer,Mark Peakman,Louis Philipson,Philip Raskin,Maria Redondo,Henry Rodriguez,William Russell,Desmond A. Schatz,Jay M. Sosenko,Lisa Spain,John Wentworth,Diane Wherrett,Darrell M. Wilson,William Winter,Anette Ziegler,Mark Anderson,Peter Antinozzi,Richard Insel,Thomas Kay,Jennifer B. Marks,Alberto Pugliese,Bart Roep,Jay S. Skyler,Jorma Toppari,Carla J. Greenbaum,Jeffrey P. Krischer,Ellen Leschek,Lisa Spain,Katarzyna Bourcier,Richard Insel,John Ridge,Jay S. Skyler,Carla J. Greenbaum,Lisa Rafkin,Jay M. Sosenko,Jay S. Skyler,Irene Santiago,Jeffrey P. Krischer,Brian Bundy,Michael Abbondondolo,Timothy Adams,Ilma Asif,Jenna Bjellquist,Matthew Boonstra,Cristina Burroughs,Mario Cleves,David Cuthbertson,Meagan DeSalvatore,Christopher Eberhard,Steve Fiske,Julie Ford,Jennifer Garmeson,Susan Geyer,Brian Hays,Courtney Henderson,Martha Henry,Kathleen Heyman,Belinda Hsiao,Christina Karges,Beata-Gabriela Koziol,Lindsay Lane,Shu Liu,Jennifer Lloyd,Kristin Maddox,Jamie Malloy,Julie Martin,Cameron McNeill,Margaret Moore,Sarah Muller,Thuy Nguyen,Jodie Nunez,Ryan O’Donnell,Melissa Parker,M.J. Pereyra,Amy Roberts,Kelly Sadler,Christine Sullivan,Roy Tamura,Elon Walker-Veras,Megan V. Warnock,Keith Wood,Rebecca Wood,Ping Xu,Vanessa Yanek,Kenneth Young,Darlene Amado,Amanda Kinderman,Ashley Leinbach,Jessica Miller,Nichole Reed,Tina Stavros,Ellen Leschek,Lisa Spain,Emily Blumberg,Sean Aas,Gerald Beck,Rose Gubitosi-Klug,Lori Laffel,Robert Vigersky,Dennis Wallace,David Brillon,Robert Veatch,Brett Loechelt,Lindsey Baden,Peter Gottlieb,Michael Green,Ellen Leschek,Adriana Weinberg,Santica Marcovina,Jerry P. Palmer,Jay Tischfield,Adriana Weinberg,William Winter,Liping Yu,Annie Shultz,Emily Batts,Arielle Pagryzinski,Mary Ramey,Meghan Tobin,Kristin Fitzpatrick,Randy Guerra,Melita Romasco,Christopher Webb,Peter Gottlieb,Maya Barr,Mary Drye,Jordan Lykens,Aaron Michels,Allison Schauwecker,Andrea Steck,Paul Wadwa,Carla J. Greenbaum,Jane Buckner,Wei Hao,Sandra Lord,Marli McCulloch-Olson,Mary Ramey,Elaine Sachter,Jenna Snavely,Meghan Tobin,Corinna Tordillos,Dana VanBuecken,Robin Goland,Analia Alvarez,Magdalena Bogun,Rachelle Gandica,Natasha Leibel,Sarah Pollak,Barney Softness,Kristen Williams,Bryce Nelson,James Amrhein,Lisa Looper,Elaine Moreland,Andrew Smith,Beth Weir,Lori Wise,Linda DiMeglio,Carmella Evans-Molina,Manasa Mantravadi,Maureen Mullen,Vanessa Patrick,Maria Spall,Stephanie Woerner,Darrell M. Wilson,Nora Arrizon-Ruiz,Tandy Aye,Laura Bachrach,Karen Barahona,Trudy Esrey,Laura Nally,Stephen E. Gitelman,Mark Anderson,Glenna Auerback,Jeanne Buchanan,Christine T. Ferrara,Karen Ko,Srinath Sanda,Christine Torok,Rebecca Wesch,Michael J. Haller,Anastasia Albanese-O'Neill,Todd Brusko,Miriam Cintron,Jennifer Hosford,Laura M. Jacobsen,Henry Rohrs,Desmond A. Schatz,Janet Silverstein,Paula Towe,David A. Baidal,Carlos Blaschke,Della Matheson,Janine Sanchez,Natalia Sanders-Branca,Jay S. Skyler,Jay M. Sosenko,Antoinette Moran,Janice Leschyshyn,Jennifer McVean,Brandon Nathan,Brittney Nelson,Beth Pappenfus,Jessica Ruedy,Anne Street,Muna Sunni,Darcy Weingartner,Dorothy Becker,Kelli DeLallo,Ana Diaz,David Groscost,Mary Beth Klein,Ingrid Libman,Karen Riley,Henry Rodriguez,Sureka Bollepalli,Rachel Brownstein,Emily Eyth,Danielle Henson,Michele Laine,Dorothy Shulman,William Russell,Faith Brendle,Anne Brown,Brenna Dixon,Justin Gregory,Dan Moore,James Thomas,Kevan Herold,Laurie Feldman,William Tamborlane,&keyword=&subject=0501,Immunology and Transplantation,