Open AccessIdentical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes
Author(s) -
Taylor M. Triolo,
Alexandra Fouts,
Laura Pyle,
Liping Yu,
Peter A. Gottlieb,
Andrea K. Steck,
Carla J. Greenbaum,
Mark A. Atkinson,
David A. Baidal,
Manuela Battaglia,
Dorothy J. Becker,
P. J. Bingley,
Emanuele Bosi,
Jane H. Buckner,
Mark A. Clements,
Peter G. Colman,
Linda A. DiMeglio,
Stephen E. Gitelman,
Robin Goland,
Kevan C. Herold,
Mikael Knip,
J. Krischer,
Åke Lernmark,
W. Moore,
Antoinette Moran,
Andrew Muir,
James L. Palmer,
Mark Peakman,
Louis H. Philipson,
P. Raskin,
María J. Redondo,
Henry Rodriguez,
William E. Russell,
Lisa M. Spain,
Desmond Schatz,
Jay M. Sosenko,
John M. Wentworth,
Diane K. Wherrett,
Darrell M. Wilson,
William E. Winter,
AnetteGabriele Ziegler,
Mark S. Anderson,
Peter A. Antinozzi,
Christophe Benoist,
Janice S. Blum,
Katarzyna Bourcier,
Peter Chase,
Michael ClareSalzler,
Raphael Clynes,
George S. Eisenbarth,
C. Garrison Fathman,
Gilman D. Grave,
Bernhard J. Hering,
Richard A. Insel,
Francine Kaufman,
Tom Kay,
Ellen W. Leschek,
J. Mahon,
Jennifer B. Marks,
Kirsti NäntöSalonen,
Gerald T. Nepom,
Tihamer Orban,
Robertson Parkman,
Mark D. Pescovitz,
John Peyman,
Alberto Pugliese,
Bart O. Roep,
Maria Grazia Roncarolo,
Peter J. Savage,
Olli Simell,
Robert Sherwin,
Mark Siegelman,
Jay S. Skyler,
James W. Thomas,
Massimo Trucco,
J. Richard Wagner,
Jeffrey P. Krischer,
Lisa Rafkin,
Catherine C. Cowie,
Mary A. Foulkes,
Heidi KrauseSteinrauf,
John M. Lachin,
Saúl Malozowski,
J P Ridge,
Stephanie J. Zafonte,
Norma S. Kenyon,
Irene Santiago,
Brian N. Bundy,
Michael Abbondondolo,
Timothy E. Adams,
Darlene Amado,
Ilma Asif,
Matthew Boonstra,
Cristina Burroughs,
David Cuthbertson,
Mary Deemer,
Christopher Eberhard,
Steve Fiske,
Julie Ford,
Jennifer Garmeson,
Heather Guillette,
Susan Geyer,
Brian Hays,
Courtney Henderson,
Martha Henry,
Kathleen Heyman,
Belinda Hsiao,
Christina Karges,
Nichole Keaton,
Amanda Kinderman,
Pat Law,
Ashely Leinbach,
Shu Liu,
Jennifer Lloyd,
Jamie Malloy,
Kristin Maddox,
Julie Martin,
Jessica Miller,
Éric Milliot,
Margaret Moore,
Sarah Müller,
Thuy Trang Nguyen,
Ryan O’Donnell,
Amy L. 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,
Doug Freeman,
Jessica Gough,
Jinin Ginem,
Moriah Granger,
Mary Holloway Michelle Kieffer,
Page Lane,
Cristin Linton,
Lavanya Nallamshetty,
Vanessa Oduah,
Yazandra Parrimon,
Kate Paulus,
Jennifer Pilger,
Joy Ramiro,
AQesha Luvon Ritzie,
Archana Sharma,
Audrey Shor,
Xiaohong Song,
AMANDA M. TERRY,
Jeanne Weinberger,
Margaret Wootten,
Pamela Harding,
Susan McDonough,
Paula McGee,
Kimberly Owens Hess,
Donna Phoebus,
Scott Quinlan,
Erica Raiden,
Emily Batts,
Chris Buddy,
Kristin Kirpatrick,
Mary Ramey,
Ann Shultz,
Chris Webb,
Melita Romesco,
Judith Fradkin,
Sean Aas,
Emily A. Blumberg,
Gerald J. Beck,
David J. Brillon,
Rose GubitosiKlug,
Lori M. Laffel,
Robert A. Vigersky,
D. H. Wallace,
Jonathan Braun,
Bernard C. Lo,
Herman Mitchell,
Ali Naji,
Jørn Nerup,
Trevor J. Orchard,
Michael W. Steffes,
Anastasios A. Tsiatis,
Robert M. Veatch,
Bernard Zinman,
Brett Loechelt,
Lindsey R. Baden,
Michael J. Green,
Adriana Weinberg,
Santica Marcovina,
Jerry P. Palmer,
Sunanda Babu,
Polly J. Bingley,
Della Matheson,
David Gómez,
Andrene McDonald,
Sandra Lidia Peralta Peña,
Massimo Pietropaolo,
Kathy Shippy,
Tyler Brown,
Angela Dove,
Marissa Hammond,
Deborah Hefty,
Jani Klein,
Kristen Kuhns,
McKenzie Letlau,
Sandra Lord,
Marli McCullochOlson,
Lisa M. Miller,
Jared Odegard,
Elaine Sachter,
Marissa St. Marie,
Kimberly Stickney,
Dana VanBuecken,
Ben Vellek,
Christine A. Webber,
Laurie Allen,
Jenna Bollyk,
Nicole Hilderman,
Hebatullah Ismail,
Steve Lamola,
Srinath Sanda,
Heather Vendettuoli,
David Tridgell,
Roshanak Monzavi,
Meredith Bock,
Lynda K. Fisher,
Mary Halvorson,
Debra Jeandron,
Mimi S. Kim,
Jamie Wood,
Mitchell E. Geffner,
Christine Salazar,
Steve Cook,
Matthew Freeby,
Mary Gallagher,
Rachelle Gandica,
Ellen Greenberg,
Amy Kurland,
Sarah Pollak,
Amy Wolk,
Mary Chan,
Linda Koplimae,
Elizabeth Levine,
Kelly Smith,
Jeniece Trast,
Carmella EvansMolina,
Robin Hufferd,
Bonnie Jagielo,
Christy Kruse,
Vanessa Patrick,
Mark Rigby,
Maria Spall,
Kim Swinney,
Jennifer Terrell,
Lyla Christner,
LeeAnn Ford,
Sheryl Lynch,
M D Stamm Menendez,
Patricia Merrill,
Cielo Alleyn,
S.D. Fay,
Jason L. Gaglia,
Brittany Resnick,
Sarah Szubowicz,
Gordon C. Weir,
Ronald Benjamin,
Debbie Conboy,
Andrea deManbey,
Richard A. Jackson,
Heyam Jalahej,
T Orban,
Alyne Ricker,
Joseph I. Wolfsdorf,
Huihui Zhang,
Tandy Aye,
Bonita K. Baker,
Karen Barahona,
Bruce A. Buckingham,
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Garry Fathman,
Radhika Snyder,
Beenu Aneja,
Maya Chatav,
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Rebecca Pyle,
Alison Rigby,
Kristin Riley,
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Christine Torok,
Rebecca Wesch,
Ivy R. Aslan,
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Celia Hamilton,
Louise Hawkins,
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Karen Ko,
Theresa M. Lee,
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Stephen M. Rosenthal,
Taninee Sahakitrungruang,
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Daniel L. Metzger,
Matt Nguyen,
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Evald Høj Christiansen,
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Mie Morimoto,
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Kimberley Norman,
Charlotte Patin,
A. Vargas,
A. Barbanica,
Pei Yu,
W. Vaidyanathan,
Robyn Osborne,
Sonal Mehra,
S. Kaster,
J. Neace,
Gabrielle Horner,
Charlotte Reeves,
Lee J. Cordrey,
Timothy C. Marrs,
D. Dowshen,
Sarah Doyle,
D. Walker,
H. Catte,
Michael Dean,
B. Drury-Brown,
Michael Hackman,
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Eleanor Curtis,
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Yajaira Zambrano
Publication year - 2018
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/dc18-0288
Subject(s) - autoantibody , medicine , type 1 diabetes , diabetes mellitus , autoimmunity , concordance , islet , immunology , endocrinology , antibody
OBJECTIVE There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.
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