Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts | Zendy

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Open Access

Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

Author(s) -

Michael Voss,

David Cuthbertson,

Mario Cleves,

Ping Xu,

Carmella EvansMolina,

Jerry P. Palmer,

María J. Redondo,

Andrea K. Steck,

Markus Lundgren,

Helena Elding Larsson,

Wayne V. Moore,

Mark A. Atkinson,

Jay M. Sosenko,

Heba M. Ismail,

Carla J. Greenbaum,

Mark Anderson,

Emanuele Bosi,

Todd M. Brusko,

Jane H. Buckner,

Mark A. Clements,

Peter G. Colman,

Mark Daniels,

Linda A. DiMeglio,

Jason L. Gaglia,

Stephen E. Gitelman,

Robin Goland,

Peter A. Gottlieb,

Michael Haller,

Kevan C. Herold,

Martin J. Hessner,

Mikael Knip,

Jeffrey P. Krischer,

Åke Lernmark,

Ingrid Libman,

Peter S. Linsley,

YF Liu,

Alice Long,

Wayne D. Moore,

Antoinette Moran,

Andrew Muir,

William E. Russell,

Lisa M. Spain,

John M. Wentworth,

Diane K. Wherrett,

Darrell M. Wilson,

William E. Winter,

Perrin C. White,

Anette G. Ziegler,

David A. Baidal,

Manuela Battaglia,

Dorothy J. Becker,

P. J. Bingley,

Mark Peakman,

Louis H. Philipson,

Philip Raskin,

Henry Rodriguez,

Desmond Schatz,

Lisa Rafkin,

Brian N. Bundy,

Michael Abbondondolo,

Timothy E. Adams,

Logan Alford,

Jenna Bjellquist,

Matthew Boonstra,

Brandie Brehon,

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 Müller,

Thuy Trang Nguyen,

Ryan O’Donnell,

Melissa M. Parker,

MJ Pereyra,

Kelly Sadler,

Roy Tamura,

Elon Walker-Veras,

Keith Wood,

Kenneth C. Young,

Ilma Asif,

Cristina Burroughs,

Meagan DeSalvatore,

Susan Geyer,

Courtney Henderson,

Martha Henry,

Beata-Gabriela Koziol,

Lindsay Lane,

Jennifer Lloyd,

Julie Martin,

Jodie Nunez,

Amy L. Roberts,

Christine Sullivan,

Megan Warnock,

Rebecca L. Wood,

Vanessa Yanek,

Emily A. Blumberg,

Sean Aas,

Gerald J. Beck,

Rose GubitosiKlug,

Dennis Wallace,

Lori M. Laffel,

Robert A. Vigersky,

Lindsey R. Baden,

Michael D. Green,

Adriana Weinberg,

David Skibinski,

Santica Marcovina,

Jay A. Tischfield,

Liping Yu,

Annie Shultz,

Emily Batts,

Arielle Pagryzinski,

Michele Patience Staal,

Kristin Fitzpatrick,

Melita Romasco,

Christopher Webb,

Mary Ramey,

Meghan Tobin,

Brenda Bradfield,

Lexie Chesshir,

Aaron W. Michels,

Morgan Quist,

Becky Robinson,

Sona Seligova,

Kimber M. Simmons,

Taylor M. Triolo,

Wei Hao,

David Kook,

Sandra Lord,

Marli McCullochOlson,

Elaine Sachter,

Jenna Snavely,

Corinna Tordillos,

V Ghobadi Dana,

Wickstrom Nancy,

Marissa Beidelschies,

Darlene Brenson-Hughes,

Jennifer Boyd,

Jennifer L. 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,

J. Sexton,

Analía Álvarez,

Magdalena Bogun,

Rachelle Gandica,

Jacqueline Y. Lonier,

Sarah Pollak,

Kristen Williams,

Amber Antich,

Kristina Cossen,

Eric I. Felner,

Margaret A. Jenkins,

Brittney Powell-Lee,

Wanda Sanchez,

Lindsay Demoe,

Danyella Dias,

Lesley Eisel,

Roze Kovalakovska,

Mary Jo Ricci,

Rebecca Stochinsky,

Eric Grubbs,

Megan Legge,

Aneyman,

Juan Manuel Sepúlveda-Sánchez,

Emily K. Sims,

Maria Spall,

Stephanie L. Woerner,

Eleonora Bianconi,

rea Bolla,

Ricardo Bonfanti,

Amelia Caretto,

Giulio Frontino,

Pauline Grogan,

rea Laurenzi,

Chiara Molinari,

Matteo Rocco Pastore,

Alessandra Petrelli,

Linda Ahlkvist,

Henrik Borg,

Berglind Jónsdóttir,

Anastasia Katsarou,

Ulrika Ulvenhag,

Tandy Aye,

Laura K. Bachrach,

Trudy Esrey,

Laura M. Nally,

Priya Prahalad,

Christopher M. Anderson,

Ramesh Srinivasan,

Benjamin Field,

Tracey Hughes,

Vicky King,

Sam Loud,

Beth Thorne,

Fatema Abdulhussein,

Natalie Aceves,

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 Wong,

Annie Abraham,

Janey Adams,

Anastasia Albanese-O’Neill,

Brittany Bruggeman,

Michael J. Claire-Salzler,

Kristin Dayton,

Paul Hiers,

Jennifer Hosford,

Laura M. Jacobsen,

John Marks,

Henry Rohrs,

Janet Silverstein,

P.D. Towe,

Minna Hirvasniemi,

Katriina Koski,

Kristiina Luopajärvi,

Heli Siljander,

Riitta Veijola,

Shan Beasley,

Melena D. Bellin,

Janice Leschyshyn,

Jennifer McVean,

Brandon M. Nathan,

Brittney Nelson,

Beth Pappenfus,

J Ruedy,

Anne Street,

Kelli Delallo,

David Groscost,

Mary Beth Klein,

Karen Riley,

Carly Shelleby,

Frederico G. S. Toledo,

L. Boyles,

Yasmin Dominguez,

Faith Brendle,

Anne Brown,

Brenna Hammel,

Jenny Leshko,

Daniel J. Moore,

Kimberly Rainer,

Tyler Smith,

James W. Thomas,

George E. Williams,

Sarah J Wright,

M Bjorasen,

Spiros Fourlanos,

Leonard C. Harrison,

Felicity Healy,

Leanne Redl,

Laurie Feldman,

William V. Tamborlane,

Stuart A. Weinzimer

Publication year - 2021

Publication title -

diabetes care

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.636

H-Index - 363

eISSN - 1935-5548

pISSN - 0149-5992

DOI - 10.2337/dc21-0226

Subject(s) - medicine , diabetes mellitus , type 2 diabetes , endocrinology , c peptide , insulin , proportional hazards model , type 1 diabetes , insulin resistance

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.

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