Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts
Authors: Michael G. Voss, David D. Cuthbertson, Mario M. Cleves, Ping Xu, Carmella Evans-Molina, Jerry P. Palmer, Maria J. Redondo, Andrea K. Steck, Markus Lundgren, Helena Larsson, Wayne V. Moore, Mark A. Atkinson, Jay M. Sosenko, Heba M. Ismail, Carla J. Greenbaum, Mark Anderson, Mark A. Atkinson, Emanuele Bosi, Todd M. Brusko, Jane Buckner, Mark Clements, Peter G. Colman, Mark Daniels, Linda DiMeglio, Carmella Evans-Molina, Jason Gaglia, Stephen E. Gitelman, Robin Goland, Peter Gottlieb, Michael Haller, Kevan Herold, Martin J. Hessner, Mikael Knip, Jeffrey P. Krischer, Ake Lernmark, Ingrid Libman, Peter S. Linsley, Yuk-Fun Liu, Alice Long, Wayne Moore, Antoinette Moran, Andrew Muir, Jerry Palmer, William Russell, Lisa Spain, Andrea Steck, John Wentworth, Diane Wherrett, Darrell M. Wilson, William Winter, Perrin White, Anette Ziegler, David A. Baidal, Manuela Battaglia, Dorothy Becker, Penelope Bingley, Mark Peakman, Louis Philipson, Philip Raskin, Maria Redondo, Henry Rodriguez, Desmond A. Schatz, Jay M. Sosenko, Carla J. Greenbaum, Jeffrey P. Krischer, Lisa Spain, Carla J. Greenbaum, Lisa Rafkin, Jay M. Sosenko, Jeffrey P. Krischer, Brian Bundy, Michael Abbondondolo, Timothy Adams, Logan Alford, Jenna Bjellquist, Matthew Boonstra, Brandie Brehon, David Cuthbertson, Christopher Eberhard, Steve Fiske, Julie Ford, Jennifer Garmeson, Cameron Hainline, Brian Hays, Kathleen Heyman, Belinda Hsiao, Christina Karges, Brett Loechelt, Shu Liu, Kristin Maddox, Colleen M. Maguire, Jamie Malloy, Alexandria Matos, Cameron McNeill, Margaret Moore, Sarah Muller, Thuy Nguyen, Ryan O’Donnell, Melissa Parker, MJ Pereyra, Kelly Sadler, Roy Tamura, Elon Walker-Veras, Keith Wood, Kenneth Young, Ilma Asif, Cristina Burroughs, Mario Cleves, Meagan DeSalvatore, Susan Geyer, Courtney Henderson, Martha Henry, Beata-Gabriela Koziol, Lindsay Lane, Jennifer Lloyd, Julie Martin, Jodie Nunez, Amy Roberts, Christine Sullivan, Megan V. Warnock, Rebecca Wood, Ping Xu, Vanessa Yanek, Lisa Spain, Emily Blumberg, Sean Aas, Gerald Beck, Rose Gubitosi-Klug, Dennis Wallace, Lori Laffel, Robert Vigersky, Lindsey Baden, Peter Gottlieb, Michael Green, Adriana Weinberg, Peter A. Gottlieb, Mark Anderson, Mark A. Atkinson, Todd M. Brusko, Jane H. Buckner, Carmella Evans-Molina, Kevan C. Herold, Martin J. Hessner, Peter S. Linsley, Alice Long, Sarah Muller, David A. G. Skibinski, Perrin White, Manuela Battaglia, Mark Peakman, Santica Marcovina, Jerry P. Palmer, Jay Tischfield, Adriana Weinberg, William Winter, Liping Yu, Annie Shultz, Emily Batts, Arielle Pagryzinski, Michele Patience Staal, Kristin Fitzpatrick, Melita Romasco, Christopher Webb, Mary Ramey, Meghan Tobin, Andrea K. Steck, Brenda Bradfield, Lexie Chesshir, Peter A. Gottlieb, Aaron W. Michels, Morgan Quist, Becky Robinson, Sona Seligova, Kimber Simmons, Taylor Triolo, Carla J. Greenbaum, Jane H. Buckner, Wei Hao, David Kook, Sandra Lord, Marli McCulloch-Olson, Mary Ramey, Elaine Sachter, Jenna Snavely, Corinna Tordillos, VanBuecken Dana, Wickstrom Nancy, Wayne Moore, Marissa Beidelschies, Darlene Brenson-Hughes, Jennifer Boyd, Mark Clements, Jennifer Dolan, Aliza Elrod, Emily Haith, Kelsee Halpin, Kelsye Howell, Jennifer James, Laura Jones, Terri Luetjen, Cassandra McClain, Ryan McDonough, Susan Mitchell, Fadi Al Muhaisen, Steve Orlich, Emily Paprocki, Barbara Seuferling, Jill Sexton, Robin Goland, Analia Alvarez, Magdalena Bogun, Rachelle Gandica, Jacqueline Lonier, Sarah Pollak, Kristen Williams, Andrew Muir, Amber Antich, Kristina Cossen, Eric Felner, Margaret Jenkins, Brittney Powell-Lee, Wanda Sanchez, Diane K. Wherrett, Lindsay Demoe, Danyella Dias, Lesley Eisel, Roze Kovalakovska, Mary Jo Ricci, Rebecca Stochinsky, Linda A. DiMeglio, Carmella Evans-Molina, Eric Grubbs, Heba M. Ismail, Megan Legge, Anna Neyman, Juan Sanchez, Emily K. Sims, Maria Spall, Stephanie Woerner, Emanuele Bosi, Eleonora Bianconi, rea Bolla, Ricardo Bonfanti, Amelia Caretto, Giulio Frontino, Pauline Grogan, rea Laurenzi, Chiara Molinari, Matteo Pastore, Alessandra Petrelli, Åke Lernmark, Linda Ahlkvist, Henrik Borg, Berglind Jónsdóttir, Anastasia Katsarou, Helena Larsson, Markus Lundgren, Ulrika Ulvenhag, Darrell M. Wilson, Tandy Aye, Laura Bachrach, Trudy Esrey, Laura Nally, Priya Prahalad, Chris Anderson, Yuk-Fun Liu, Ramesh Srinivasan, Benjamin Field, Tracey Hughes, Vicky King, Sam Loud, Beth Thorne, Stephen E. Gitelman, Fatema Abdulhussein, Natalie Aceves, Mark S. Anderson, Glenna Auerback, Jeanne Buchanan, Hannah Chesser, Abby Cobb-Walch, Laura Dapkus, Karen Ko, Janet Lee, Roger Long, Isabella Niu, Srinath Sanda, Caroline Schulmeister, Christine Torok, Rebecca Wesch, Jenise Haller, Michael J. Wong, Annie Abraham, Janey Adams, Anastasia Albanese-O'Neill, Mark A. Atkinson, Brittany Bruggeman, Todd M. Brusko, Michael J. Claire-Salzler, Kristin Dayton, Paul Hiers, Jennifer Hosford, Laura M. Jacobsen, John Marks, Henry Rohrs, Desmond A. Schatz, Janet Silverstein, Paula Towe, William E. Winter, Mikael Knip, Minna Hirvasniemi, Katriina Koski, Kristiina Luopajärvi, Heli Siljander, Riitta Veijola, Antoinette M. Moran, Shannon Beasley, Melena D. Bellin, Janice Leschyshyn, Jennifer McVean, Brandon M. Nathan, Brittney Nelson, Beth Pappenfus, Jessica Ruedy, Anne Street, Dorothy J. Becker, Ingrid M. Libman, Kelli DeLallo, David Groscost, Mary Beth Klein, Karen Riley, Carly Shelleby, Frederico Toledo, Perrin White, Lauren Boyles, Yasmin Dominguez, Philip Raskin, William E. Russell, Faith Brendle, Anne Brown, Brenna Hammel, Jenny Leshko, Daniel J. Moore, Kimberly Rainer, Tyler Smith, James W. Thomas, George Williams, Sarah Wright, Peter Colman, Marika Bjorasen, Spiros Fourlanos, Leonard C. Harrison, Felicity Healy, Leanne Redl, John M. Wentworth, Kevan C. Herold, Laurie Feldman, William V. Tamborlane, Stuart A. Weinzimer
Journal: Diabetes Care (2021)

OBJECTIVE To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose &amp;gt;30 min and time to peak C-peptide &amp;gt;60 min (P &amp;lt; 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P &amp;lt; 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.