Open AccessMetabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program
Author(s) -
ZsuZsu Chen,
Jinxi Liu,
Jordan Morningstar,
Brandy M. HeckmanStoddard,
Christine G. Lee,
Samuel DagogoJack,
Jane F. Ferguson,
Richard F. Hamman,
William C. Knowler,
Kieren J. Mather,
Leigh Perreault,
José C. Florez,
Thomas J. Wang,
Clary B. Clish,
Marinella Temprosa,
Robert E. Gerszten,
George A. Bray,
Kishore M. Gadde,
Annie Chatellier,
Jennifer Arceneaux,
Amber Dragg,
Crystal Duncan,
Frank L. Greenway,
Daniel S. Hsia,
Erma Levy,
Monica Lockett,
Donna H. Ryan,
David A. Ehrmann,
Margaret J. Matulik,
Kirsten Czech,
Catherine DeSandre,
Barry J. Goldstein,
Kevin Furlong,
Kellie A. Smith,
Wendi Wildman,
Constance Pepe,
Ronald Goldberg,
Jeanette Calles,
Juliet Ojito,
Sumaya Castillo-Florez,
Hermes Flórez,
Anna Giannella,
Olga Lara,
Beth Veciana,
Steven M. Haffner,
Helen P. Hazuda,
Maria G. Montez,
Kathy Hattaway,
Carlos Lorenzo,
Arlene Martinez,
Tatiana Walker,
Dana Dabelea,
Lisa Testaverde,
Denise Anderson,
Alexis Bouffard,
Tonya Jenkins,
Dione Lenz,
David W. Price,
Sheila C. Steinke,
Edward S. Horton,
Catherine S. Poirier,
Kati Swift,
Enrique Caballero,
Barbara Fargnoli,
Ashley Guidi,
Mathew Guido,
Sharon D. Jackson,
Lori Lambert,
Kathleen E. Lawton,
Sarah Ledbury,
Jessica Sansoucy,
Jeanne Spellman,
Steven E. Kahn,
Brenda K. Montgomery,
Wilfred Y. Fujimoto,
Robert H. Knopp,
Edward W. Lipkin,
Ivy Morgan-Taggart,
Anne Murillo,
Lonnese Taylor,
April Thomas,
Elaine C. Tsai,
Dace Trence,
Abbas E. Kitabchi,
Mary E. Murphy,
Laura Taylor,
Jennifer Dolgoff,
Debra Clark,
Uzoma N. Ibebuogu,
Helen Lambeth,
Harriet Ricks,
Lily M.K. Rutledge,
Judith E. Soberman,
Mark E. Molitch,
Boyd E. Metzger,
Mariana K. Johnson,
Mimi M. Giles,
Diane Larsen,
Samsam C. Pen,
David M. Nathan,
Mary Larkin,
Charles McKitrick,
Heather Turgeon,
Ellen Anderson,
Laurie Bissett,
Kristy Bondi,
Enrico Cagliero,
Kali D’Anna,
Linda M. Delahanty,
Valerie Goldman,
Peter Lou,
Alexandra Poulos,
Elyse Raymond,
Christine Stevens,
Beverly Tseng,
Elizabeth BarrettConnor,
Mary Lou Carrion-Petersen,
Lauren N. Claravall,
Jonalle M. Dowden,
Javiva Horne,
Diana Leos,
Sundar Mudaliar,
Jean Louise M. Smith,
Simona Szerdi Janisch,
Karen Vejvoda,
F. Xavier PiSunyer,
Jane E. Lee,
Sandra T. Foo,
Susan Hagamen,
David G. Marrero,
Susie M. Kelly,
Paula Putenney,
Marcia A. Jackson,
Gina McAtee,
Ronald T. Ackermann,
Carolyn M. Cantrell,
Edwin S. Fineberg,
Angela Hadden,
M.S. Kirkman,
Erin O’Kelly Phillips,
Paris Roach,
Robert E. Ratner,
Vanita R. Aroda,
Sue Shapiro,
Catherine Bavido-Arrage,
Peggy Gibbs,
Gabriel I. Uwaifo,
Renee Wiggins,
Mohammed Saad,
Karol E. Watson,
Medhat Botrous,
Sujata Jinagouda,
Maria Budget,
Claudia Conzues,
Perpetua Magpuri,
Kathy Ngo,
Kathy Xapthalamous,
Neil H. White,
Angela L. Brown,
Samia Das,
Prajakta Khare-Ranade,
Tamara Stich,
Ana Santiago,
Cormarie Wernimont,
Christopher D. Saudek,
Sherita Hill Golden,
Tracy Whittington,
Frederick L. Brancati,
Jeanne M. Clark,
Alicia C. Greene,
Dawn Jiggetts,
Henry Mosley,
John Reusing,
Richard R. Rubin,
Shawne Stephens,
Evonne Utsey,
David S. Schade,
Karwyn S. Adams,
Claire Hemphill,
Penny Hyde,
Janene L. Canady,
Kathleen Colleran,
Ysela Gonzales,
Doris A. Hernandez-McGinnis,
Carolyn King,
Jill P. Crandall,
Janet O. Brown,
Gilda Trandafirescu,
Elsie Adorno,
Helena Duffy,
Angela Goldstein,
Jennifer Lukin,
Helen Martinez,
Dorothy Pompi,
Harry Shamoon,
Jonathan Scheindlin,
Elizabeth A. Walker,
Judith WylieRosett,
Trevor J. Orchard,
Andrea M. Kriska,
Susan Jeffries,
M. Kaye Kramer,
Marie Smith,
Catherine Benchoff,
Stephanie Guimond,
Jessica Pettigrew,
Debra Rubinstein,
Linda Semler,
Elizabeth M. Venditti,
Valarie Weinzierl,
Richard Arakaki,
Narleen K. Baker-Ladao,
Mae K. Isonaga,
Nina E. Bermudez,
Marjorie K. Mau,
John S. Melish,
Robin E. Yamamoto,
Norman Cooeyate,
Alvera Enote,
Mary A. Hoskin,
Camille Natewa,
Carol Percy,
Kelly J. Acton,
Vickie L. Andre,
Roz Barber,
Shandiin Begay,
Brian C. Bucca,
Sherron Cook,
Jeff Curtis,
Charlotte Dodge,
Matthew S. Doughty,
Jason Kurland,
Justin Glass,
Martia Glass,
Robert L. Hanson,
Louise E. Ingraham,
Kathleen M. Kobus,
Jonathan Krakoff,
Catherine Manus,
Cherie McCabe,
Sara Michaels,
Tina Morgan,
Julie A. Nelson,
Christopher Piromalli,
Robert J. Roy,
Sandra Sangster,
Miranda Smart,
Darryl Tonemah,
Rachel Williams,
Charlton Wilson,
Sarah Fowler,
Michael Larsen,
Tina Brenneman,
Hanna Sherif,
Sharon L. Edelstein,
Solome Abebe,
Julie Bamdad,
Melanie Barkalow,
Joel Bethepu,
Tsedenia Bezabeh,
Nicole Butler,
Jackie Callaghan,
Caitlin E. Carter,
Costas A. Christophi,
Gregory M. Dwyer,
Mary A. Foulkes,
Yuping Gao,
Robert Gooding,
Adrienne Gottlieb,
Nisha Grover,
Heather J. Hoffman,
Ashley H. Tjaden,
Kathleen Jablonski,
Richard J. Katz,
Preethy Kolinjivadi,
John M. Lachin,
Yong Ma,
Qing Pan,
Susan Reamer,
Alla Sapozhnikova,
Valerie Weinzierl,
Santica Marcovina,
Greg Strylewicz,
John J. Albers,
Judith Fradkin,
Sanford Garfield,
Edward W. Gregg,
Ping Zhang,
David Altshuler,
Liana K. Billings,
Ling Chen,
Maegan Harden,
Toni I. Pollin,
Alan R. Shuldiner,
Paul W. Franks,
MarieFrance Hivert
Publication year - 2019
Publication title -
diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.219
H-Index - 330
eISSN - 1939-327X
pISSN - 0012-1797
DOI - 10.2337/db19-0236
Subject(s) - metformin , type 2 diabetes , diabetes mellitus , medicine , metabolite , placebo , endocrinology , pharmacology , bioinformatics , biology , alternative medicine , pathology
Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.
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