Randomized Controlled Trial

. 2020 Jan;69(1):112-120.

doi: 10.2337/db19-0097. Epub 2019 Oct 21.

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

Jordi Merino^{1

2

3

4

5}, Kathleen A Jablonski⁶, Josep M Mercader^{1

2

3}, Steven E Kahn⁷, Ling Chen^{1

2

3}, Maegan Harden⁸, Linda M Delahanty^{2

4}, Maria Rosario G Araneta⁹, Geoffrey A Walford^{1

2}, Suzanne B R Jacobs^{1

2

3}, Uzoma N Ibebuogu¹⁰, Paul W Franks^{11

12

13}, William C Knowler¹⁴, Jose C Florez; Diabetes Prevention Program Research Group

Collaborators, Affiliations

Collaborators

Diabetes Prevention Program Research Group:
George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, Daniel Hsia, Erma Levy, Monica Lockett, Donna H Ryan, David Ehrmann, Margaret J Matulik, Kirsten Czech, Catherine DeSandre, Barry J Goldstein, Kevin Furlong, Kellie A Smith, Wendi Wildman, Constance Pepe, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, 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, Steven E Kahn, Brenda K Montgomery, Wilfred 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 Dagogo-Jack, Mary E Murphy, Laura Taylor, Jennifer Dolgoff, Debra Clark, Uzoma 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 Delahanty, Jose C Florez, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F Xavier Pi-Sunyer, 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, Mario S Kirkman, Erin O'Kelly Phillips, Paris J Roach, Robert E Ratner, Vanita Aroda, Sue Shapiro, Catherine Bavido-Arrage, Peggy Gibbs, Gabriel Uwaifo, Renee Wiggins, Mohammed F Saad, Karol 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 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 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 Wylie-Rosett, Trevor Orchard, Andrea Kriska, Susan Jeffries, M Kaye Kramer, Marie Smith, Catherine Benchoff, Stephanie Guimond, Jessica Pettigrew, Debra Rubinstein, Linda Semler, Elizabeth Venditti, Valarie Weinzierl, Richard F Arakaki, Narleen K Baker-Ladao, Mae K Isonaga, Nina E Bermudez, Marjorie K Mau, John S Melish, Robin E Yamamoto, William C Knowler, Norman Cooeyate, Alvera Enote, Mary A Hoskin, Camille Natewa, Carol A 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 P 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, Costas Christophi, Gregory M Dwyer, Mary Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Nisha Grover, Heather Hoffman, Ashley Hogan Tjaden, Kathleen Jablonski, Richard Katz, Preethy Kolinjivadi, John M Lachin, Yong Ma, Qing Pan, Susan Reamer, Alla Sapozhnikova, Elizabeth M Venditti, Andrea M Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, Greg Strylewicz, John Albers, Judith Fradkin, Sanford Garfield, Christine Lee, Edward Gregg, Ping Zhang, Jose C Florez, David Altshuler, Liana K Billings, Ling Chen, Maegan Harden, Robert L Hanson, William C Knowler, Toni I Pollin, Alan R Shuldiner, Kathleen Jablonski, Paul W Franks, Marie-France Hivert

Affiliations

¹ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
² Diabetes Unit, Massachusetts General Hospital, Boston, MA.
³ Programs in Metabolism and Medical and Population Genetics, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA.
⁴ Department of Medicine, Harvard Medical School, Boston, MA.
⁵ Research Unit on Lipids and Atherosclerosis, CIBERDEM, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
⁶ The Biostatistics Center, Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
⁷ Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA.
⁸ Genomics Platform, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA.
⁹ Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.
¹⁰ Division of Cardiovascular Diseases, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN.
¹¹ Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmo, Sweden.
¹² Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
¹³ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
¹⁴ Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.

PMID: 31636172
PMCID: PMC6925585
DOI: 10.2337/db19-0097

Randomized Controlled Trial

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

Jordi Merino et al. Diabetes. 2020 Jan.

. 2020 Jan;69(1):112-120.

doi: 10.2337/db19-0097. Epub 2019 Oct 21.

Authors

Collaborators

Diabetes Prevention Program Research Group:
George A Bray, Kishore Gadde, Annie Chatellier, Jennifer Arceneaux, Amber Dragg, Crystal Duncan, Frank L Greenway, Daniel Hsia, Erma Levy, Monica Lockett, Donna H Ryan, David Ehrmann, Margaret J Matulik, Kirsten Czech, Catherine DeSandre, Barry J Goldstein, Kevin Furlong, Kellie A Smith, Wendi Wildman, Constance Pepe, Ronald B Goldberg, Jeanette Calles, Juliet Ojito, Sumaya Castillo-Florez, Hermes J Florez, 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, Steven E Kahn, Brenda K Montgomery, Wilfred 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 Dagogo-Jack, Mary E Murphy, Laura Taylor, Jennifer Dolgoff, Debra Clark, Uzoma 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 Delahanty, Jose C Florez, Valerie Goldman, Peter Lou, Alexandra Poulos, Elyse Raymond, Christine Stevens, Beverly Tseng, Elizabeth Barrett-Connor, Mary Lou Carrion-Petersen, Lauren N Claravall, Jonalle M Dowden, Javiva Horne, Diana Leos, Sundar Mudaliar, Jean Smith, Simona Szerdi Janisch, Karen Vejvoda, F Xavier Pi-Sunyer, 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, Mario S Kirkman, Erin O'Kelly Phillips, Paris J Roach, Robert E Ratner, Vanita Aroda, Sue Shapiro, Catherine Bavido-Arrage, Peggy Gibbs, Gabriel Uwaifo, Renee Wiggins, Mohammed F Saad, Karol 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 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 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 Wylie-Rosett, Trevor Orchard, Andrea Kriska, Susan Jeffries, M Kaye Kramer, Marie Smith, Catherine Benchoff, Stephanie Guimond, Jessica Pettigrew, Debra Rubinstein, Linda Semler, Elizabeth Venditti, Valarie Weinzierl, Richard F Arakaki, Narleen K Baker-Ladao, Mae K Isonaga, Nina E Bermudez, Marjorie K Mau, John S Melish, Robin E Yamamoto, William C Knowler, Norman Cooeyate, Alvera Enote, Mary A Hoskin, Camille Natewa, Carol A 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 P 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, Costas Christophi, Gregory M Dwyer, Mary Foulkes, Yuping Gao, Robert Gooding, Adrienne Gottlieb, Nisha Grover, Heather Hoffman, Ashley Hogan Tjaden, Kathleen Jablonski, Richard Katz, Preethy Kolinjivadi, John M Lachin, Yong Ma, Qing Pan, Susan Reamer, Alla Sapozhnikova, Elizabeth M Venditti, Andrea M Kriska, Linda Semler, Valerie Weinzierl, Santica Marcovina, Greg Strylewicz, John Albers, Judith Fradkin, Sanford Garfield, Christine Lee, Edward Gregg, Ping Zhang, Jose C Florez, David Altshuler, Liana K Billings, Ling Chen, Maegan Harden, Robert L Hanson, William C Knowler, Toni I Pollin, Alan R Shuldiner, Kathleen Jablonski, Paul W Franks, Marie-France Hivert

Affiliations

¹ Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
² Diabetes Unit, Massachusetts General Hospital, Boston, MA.
³ Programs in Metabolism and Medical and Population Genetics, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA.
⁴ Department of Medicine, Harvard Medical School, Boston, MA.
⁵ Research Unit on Lipids and Atherosclerosis, CIBERDEM, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
⁶ The Biostatistics Center, Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
⁷ Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA.
⁸ Genomics Platform, Eli and Edythe L. Broad Institute of MIT and Harvard, Cambridge, MA.
⁹ Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA.
¹⁰ Division of Cardiovascular Diseases, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN.
¹¹ Genetic & Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmo, Sweden.
¹² Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
¹³ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
¹⁴ Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.

PMID: 31636172
PMCID: PMC6925585
DOI: 10.2337/db19-0097

Abstract

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 (P _interaction > 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.

Trial registration: ClinicalTrials.gov NCT00004992.

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous