Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts
Author:
Voss Michael G.1, Cuthbertson David D.2, Cleves Mario M.2, Xu Ping2, Evans-Molina Carmella3, Palmer Jerry P.4, Redondo Maria J.5, Steck Andrea K.6, Lundgren Markus7, Larsson Helena7, Moore Wayne V.8, Atkinson Mark A.9, Sosenko Jay M.10, Ismail Heba M.3ORCID, Greenbaum Carla J., Anderson Mark, Atkinson Mark A., Bosi Emanuele, Brusko Todd M., Buckner Jane, Clements Mark, Colman Peter G., Daniels Mark, DiMeglio Linda, Evans-Molina Carmella, Gaglia Jason, Gitelman Stephen E., Goland Robin, Gottlieb Peter, Haller Michael, Herold Kevan, Hessner Martin J., Knip Mikael, Krischer Jeffrey P., Lernmark Ake, Libman Ingrid, Linsley Peter S., Liu Yuk-Fun, Long Alice, Moore Wayne, Moran Antoinette, Muir Andrew, Palmer Jerry, Russell William, Spain Lisa, Steck Andrea, Wentworth John, Wherrett Diane, Wilson Darrell M., Winter William, White Perrin, Ziegler Anette, Baidal David A., Battaglia Manuela, Becker Dorothy, Bingley Penelope, Peakman Mark, Philipson Louis, Raskin Philip, Redondo Maria, Rodriguez Henry, Schatz Desmond A., Sosenko Jay M., Greenbaum Carla J., Krischer Jeffrey P., Spain Lisa, Greenbaum Carla J., Rafkin Lisa, Sosenko Jay M., Krischer Jeffrey P., Bundy Brian, Abbondondolo Michael, Adams Timothy, Alford Logan, Bjellquist Jenna, Boonstra Matthew, Brehon Brandie, Cuthbertson David, Eberhard Christopher, Fiske Steve, Ford Julie, Garmeson Jennifer, Hainline Cameron, Hays Brian, Heyman Kathleen, Hsiao Belinda, Karges Christina, Loechelt Brett, Liu Shu, Maddox Kristin, Maguire Colleen M., Malloy Jamie, Matos Alexandria, McNeill Cameron, Moore Margaret, Muller Sarah, Nguyen Thuy, O’Donnell Ryan, Parker Melissa, Pereyra MJ, Sadler Kelly, Tamura Roy, Walker-Veras Elon, Wood Keith, Young Kenneth, Asif Ilma, Burroughs Cristina, Cleves Mario, DeSalvatore Meagan, Geyer Susan, Henderson Courtney, Henry Martha, Koziol Beata-Gabriela, Lane Lindsay, Lloyd Jennifer, Martin Julie, Nunez Jodie, Roberts Amy, Sullivan Christine, Warnock Megan V., Wood Rebecca, Xu Ping, Yanek Vanessa, Spain Lisa, Blumberg Emily, Aas Sean, Beck Gerald, Gubitosi-Klug Rose, Wallace Dennis, Laffel Lori, Vigersky Robert, Baden Lindsey, Gottlieb Peter, Green Michael, Weinberg Adriana, Gottlieb Peter A., Anderson Mark, Atkinson Mark A., Brusko Todd M., Buckner Jane H., Evans-Molina Carmella, Herold Kevan C., Hessner Martin J., Linsley Peter S., Long Alice, Muller Sarah, Skibinski David A. G., White Perrin, Battaglia Manuela, Peakman Mark, Marcovina Santica, Palmer Jerry P., Tischfield Jay, Weinberg Adriana, Winter William, Yu Liping, Shultz Annie, Batts Emily, Pagryzinski Arielle, Staal Michele Patience, Fitzpatrick Kristin, Romasco Melita, Webb Christopher, Ramey Mary, Tobin Meghan, Steck Andrea K., Bradfield Brenda, Chesshir Lexie, Gottlieb Peter A., Michels Aaron W., Quist Morgan, Robinson Becky, Seligova Sona, Simmons Kimber, Triolo Taylor, Greenbaum Carla J., Buckner Jane H., Hao Wei, Kook David, Lord Sandra, McCulloch-Olson Marli, Ramey Mary, Sachter Elaine, Snavely Jenna, Tordillos Corinna, Dana VanBuecken, Nancy Wickstrom, Moore Wayne, Beidelschies Marissa, Brenson-Hughes Darlene, Boyd Jennifer, Clements Mark, Dolan Jennifer, Elrod Aliza, Haith Emily, Halpin Kelsee, Howell Kelsye, James Jennifer, Jones Laura, Luetjen Terri, McClain Cassandra, McDonough Ryan, Mitchell Susan, Muhaisen Fadi Al, Orlich Steve, Paprocki Emily, Seuferling Barbara, Sexton Jill, Goland Robin, Alvarez Analia, Bogun Magdalena, Gandica Rachelle, Lonier Jacqueline, Pollak Sarah, Williams Kristen, Muir Andrew, Antich Amber, Cossen Kristina, Felner Eric, Jenkins Margaret, Powell-Lee Brittney, Sanchez Wanda, Wherrett Diane K., Demoe Lindsay, Dias Danyella, Eisel Lesley, Kovalakovska Roze, Ricci Mary Jo, Stochinsky Rebecca, DiMeglio Linda A., Evans-Molina Carmella, Grubbs Eric, Ismail Heba M., Legge Megan, Neyman Anna, Sanchez Juan, Sims Emily K., Spall Maria, Woerner Stephanie, Bosi Emanuele, Bianconi Eleonora, Bolla rea, Bonfanti Ricardo, Caretto Amelia, Frontino Giulio, Grogan Pauline, Laurenzi rea, Molinari Chiara, Pastore Matteo, Petrelli Alessandra, Lernmark Åke, Ahlkvist Linda, Borg Henrik, Jónsdóttir Berglind, Katsarou Anastasia, Larsson Helena, Lundgren Markus, Ulvenhag Ulrika, Wilson Darrell M., Aye Tandy, Bachrach Laura, Esrey Trudy, Nally Laura, Prahalad Priya, Anderson Chris, Liu Yuk-Fun, Srinivasan Ramesh, Field Benjamin, Hughes Tracey, King Vicky, Loud Sam, Thorne Beth, Gitelman Stephen E., Abdulhussein Fatema, Aceves Natalie, Anderson Mark S., Auerback Glenna, Buchanan Jeanne, Chesser Hannah, Cobb-Walch Abby, Dapkus Laura, Ko Karen, Lee Janet, Long Roger, Niu Isabella, Sanda Srinath, Schulmeister Caroline, Torok Christine, Wesch Rebecca, Haller Jenise, Wong Michael J., Abraham Annie, Adams Janey, Albanese-O'Neill Anastasia, Atkinson Mark A., Bruggeman Brittany, Brusko Todd M., Claire-Salzler Michael J., Dayton Kristin, Hiers Paul, Hosford Jennifer, Jacobsen Laura M., Marks John, Rohrs Henry, Schatz Desmond A., Silverstein Janet, Towe Paula, Winter William E., Knip Mikael, Hirvasniemi Minna, Koski Katriina, Luopajärvi Kristiina, Siljander Heli, Veijola Riitta, Moran Antoinette M., Beasley Shannon, Bellin Melena D., Leschyshyn Janice, McVean Jennifer, Nathan Brandon M., Nelson Brittney, Pappenfus Beth, Ruedy Jessica, Street Anne, Becker Dorothy J., Libman Ingrid M., DeLallo Kelli, Groscost David, Klein Mary Beth, Riley Karen, Shelleby Carly, Toledo Frederico, White Perrin, Boyles Lauren, Dominguez Yasmin, Raskin Philip, Russell William E., Brendle Faith, Brown Anne, Hammel Brenna, Leshko Jenny, Moore Daniel J., Rainer Kimberly, Smith Tyler, Thomas James W., Williams George, Wright Sarah, Colman Peter, Bjorasen Marika, Fourlanos Spiros, Harrison Leonard C., Healy Felicity, Redl Leanne, Wentworth John M., Herold Kevan C., Feldman Laurie, Tamborlane William V., Weinzimer Stuart A.,
Affiliation:
1. Department of Medicine, Indiana University, School of Medicine, Indianapolis, IN 2. Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida 3. Department of Pediatrics, Indiana University, School of Medicine, Indianapolis, IN 4. Veterans Affairs Puget Sound Health Care System, Seattle, WA 5. Texas Children’s Hospital, Baylor College of Medicine, Houston, TX 6. Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO 7. Unit for Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden 8. Division of Endocrinology and Diabetes, Children’s Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, MO 9. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 10. Division of Endocrinology, Diabetes, and Metabolism, University of Miami, Miami, FL
Abstract
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 >30 min and time to peak C-peptide >60 min (P < 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 < 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.
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
4 articles.
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