Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors | Zendy

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Open Access

Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Author(s) -

Jordi Merino,

Kathleen A. Jablonski,

Josep M. Mercader,

Steven E. Kahn,

Ling Chen,

Maegan Harden,

Linda M. Delahanty,

Maria Rosario G. Araneta,

Geoffrey Walford,

Suzanne B.R. Jacobs,

Uzoma N. Ibebuogu,

Paul W. Franks,

William C. Knowler,

José C. Florez,

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,

Richard F. Hamman,

Dana Dabelea,

Lisa Testaverde,

Denise Anderson,

Alexis Bouffard,

Tonya Jenkins,

Dione Lenz,

Leigh Perreault,

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,

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,

Samuel DagogoJack,

Mary E. Murphy,

Laura Taylor,

Jennifer Dolgoff,

Debra Clark,

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,

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,

Kieren J. Mather,

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,

Marinella Temprosa,

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,

Christopher 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,

Christine G. Lee,

Edward W. Gregg,

Ping Zhang,

David Altshuler,

Liana K. Billings,

Toni I. Pollin,

Alan R. Shuldiner,

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/db19-0097

Subject(s) - crfs , medicine , diabetes mellitus , coronary artery disease , metformin , placebo , type 2 diabetes , psychological intervention , endocrinology , alternative medicine , conditional random field , pathology , psychiatry , natural language processing , computer science

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

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