Prospective association of a genetic risk score and lifestyle intervention with cardiovascular morbidity and mortality among individuals with type 2 diabetes: the Look AHEAD randomised controlled trial
Look AHEAD Research Group, Jeanne M McCaffery, Andrea Anderson, John P Bantle, Robert I Berkowitz, George A Bray, Lawrence Cheskin, Jeanne M Clark, Jeffrey M Curtis, Linda M Delahanty, Mary Evans, John P Foreyt, Stephen Glasser, Edward W Gregg, Robert L Hanson, Helen P Hazuda, James O Hill, Edward S Horton, Gordon S Huggins, John M Jakicic, Robert W Jeffery, Karen C Johnson, Steven E Kahn, David E Kelley, Abbas E Kitabchi, William C Knowler, Cora E Lewis, Maria G Montez, Anne Kure, David M Nathan, Ebenezer Nyenwe, Nicholas M Pajewski, George D Papandonatos, Jennifer Patricio, Inga Peter, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, Thomas A Wadden, Lynne E Wagenknecht, Rena R Wing, Cora E Lewis, Lawrence Cheskin, Richard S Crow, Lawrence M Friedman, Stephen Glasser, Patricia Hogan, Karen C Johnson, David Lefkowitz, Ron Prineas, J Bruce Redmon, Patrick S Reynolds, Monika Safford, Tandaw Samdarshi, Carrie C Williams, John M Jakicic, James O Hill, Ashok Balasubramanyam, George Blackburn, Lawton S Cooper, Kathy M Dotson, Mary Evans, Gary Foster, Jeanne McCaffery, David Reboussin, George A Bray, Sheikilya Thomas, Richard S Crow, Mary Evans, Edward W Gregg, James O Hill, Amelia Hodges, Robert W Jeffery, Tina Killean, Maria G Montez, David Reboussin, Lee Swartz, Richard Rubin, Frederick L Brancati, Judy L Bahnson, Kathy M Dotson, Mark A Espeland, Mary Evans, Cora E Lewis, Barbara J Maschak-Carey, David M Nathan, Delia S West, Rena R Wing, Jacqueline Wesche-Thobaben, Anne Peters, Jeanne M Clark, Abbas E Kitabchi, Judy L Bahnson, Caitlin Egan, Mary Evans, Valerie Goldman, Amelia Hodges, Dominique Limprevil-Divers, Juliet Mancino, Cathy Manus, Tricia Skarphol, J Lee Taylor, Henry Glick, William C Knowler, Alain G Bertoni, Brenda L Craven, Kathy M Dotson, Mark A Espeland, Mary Evans, Richard Hamman, Don G Hire, Tina Killean, Michael S Lawlor, Dominique Limprevil-Divers, Maria G Montez, Julia T Rushing, Adam G Tsai, David F Williamson, Ping Zhang, Judy L Bahnson, Mark A Espeland, Mary Evans, Barbara Harrison, Xavier Pi-Sunyer, Lynne E Wagenknecht, Rena R Wing, Barbara J Maschak-Carey, Marsha Miller, Brenda Montgomery, Judy L Bahnson, Paula Bolin, Kathy M Dotson, Caitlin Egan, Mary Evans, Molly Gee, Siran Ghazarian, Valerie Goldman, Carolyn Gresham, Barbara Harrison, Diane Hirsch, Amelia Hodges, Sharon D Jackson, Tina Killean, Helen Lambeth, Dominique Limprevil-Divers, Maria G Montez, Moana Mosby, Anne Murillo, Jennifer Patricio, Rebecca Reeves, Tricia Skarphol, Allison Strate, Lee Swartz, Sheikilya Thomas, Carolyn Thorson, Jacqueline Wesche-Thobaben, Carrie C Williams, Rena R Wing, Jeanne M Clark, Donna H Ryan, Mark A Espeland, Edward W Gregg, Amelia Hodges, Van S Hubbard, Karen C Johnson, Steven E Kahn, Abbas E Kitabchi, William C Knowler, Dominique Limprevil-Divers, David M Nathan, Xavier Pi-Sunyer, Monika Safford, Lynne E Wagenknecht, Carrie C Williams, Rena R Wing, Susan Z Yanovski, Jennifer Patricio, Lynne Lichtermann, Jennifer Arceneaux, Jeanne Charleston, Kathy M Dotson, Caitlin Egan, Mary Evans, Richard Foushee, Molly Gee, Carolyn Gresham, Nancy J Hall, Ruby Johnson, Robert Knopp, Helen Lambeth, Rebecca Reeves, Richard Rubin, Allison Strate, Brent Van Dorsten, Frederick L Brancati, David Kelly, Judy L Bahnson, Alain G Bertoni, Lawton S Cooper, Jeffrey M Curtis, Sarah A Gaussoin, Siran Ghazarian, Van S Hubbard, Steven E Kahn, Barbara J Maschak-Carey, Anne Murillo, Anne Peters, Xavier Pi-Sunyer, Susan Z Yanovski, Rena R Wing, Xavier Pi-Sunyer, Frederick L Brancati, George A Bray, Jeanne M Clark, Jeffrey M Curtis, Mark A Espeland, Mary Evans, John P Foreyt, Steven Haffner, Barabara Harrison, Helen P Hazuda, James O Hill, Edward S Horton, John M, Robert W Jeffery, Karen C Johnson, Steven E Kahn, David Kelly, Abbas E Kitabchi, William C Knowler, Cora E Lewis, David M Nathan, Anne Peters, Thomas A Wadden, Lynne E Wagenknecht, Thomas A Wadden, Delia S West, John P Bantle, Robert I Berkowitz, Paula Bolin, Barbara Cerniauskas, Linda Delahanty, Kathy M Dotson, Mary Evans, John P Foreyt, Edward W Gregg, Helen P Hazuda, John M Jakicic, Shiriki Kumanyika, Marsha Miller, Carmen Pal, Rebecca Reeves, Jack Rejeski, Amy D Rickman, Mara Vitolins, Don Williamson, Rena R Wing, Susan Z Yanovski, Look AHEAD Research Group, Jeanne M McCaffery, Andrea Anderson, John P Bantle, Robert I Berkowitz, George A Bray, Lawrence Cheskin, Jeanne M Clark, Jeffrey M Curtis, Linda M Delahanty, Mary Evans, John P Foreyt, Stephen Glasser, Edward W Gregg, Robert L Hanson, Helen P Hazuda, James O Hill, Edward S Horton, Gordon S Huggins, John M Jakicic, Robert W Jeffery, Karen C Johnson, Steven E Kahn, David E Kelley, Abbas E Kitabchi, William C Knowler, Cora E Lewis, Maria G Montez, Anne Kure, David M Nathan, Ebenezer Nyenwe, Nicholas M Pajewski, George D Papandonatos, Jennifer Patricio, Inga Peter, Anne Peters, Xavier Pi-Sunyer, Henry Pownall, Thomas A Wadden, Lynne E Wagenknecht, Rena R Wing, Cora E Lewis, Lawrence Cheskin, Richard S Crow, Lawrence M Friedman, Stephen Glasser, Patricia Hogan, Karen C Johnson, David Lefkowitz, Ron Prineas, J Bruce Redmon, Patrick S Reynolds, Monika Safford, Tandaw Samdarshi, Carrie C Williams, John M Jakicic, James O Hill, Ashok Balasubramanyam, George Blackburn, Lawton S Cooper, Kathy M Dotson, Mary Evans, Gary Foster, Jeanne McCaffery, David Reboussin, George A Bray, Sheikilya Thomas, Richard S Crow, Mary Evans, Edward W Gregg, James O Hill, Amelia Hodges, Robert W Jeffery, Tina Killean, Maria G Montez, David Reboussin, Lee Swartz, Richard Rubin, Frederick L Brancati, Judy L Bahnson, Kathy M Dotson, Mark A Espeland, Mary Evans, Cora E Lewis, Barbara J Maschak-Carey, David M Nathan, Delia S West, Rena R Wing, Jacqueline Wesche-Thobaben, Anne Peters, Jeanne M Clark, Abbas E Kitabchi, Judy L Bahnson, Caitlin Egan, Mary Evans, Valerie Goldman, Amelia Hodges, Dominique Limprevil-Divers, Juliet Mancino, Cathy Manus, Tricia Skarphol, J Lee Taylor, Henry Glick, William C Knowler, Alain G Bertoni, Brenda L Craven, Kathy M Dotson, Mark A Espeland, Mary Evans, Richard Hamman, Don G Hire, Tina Killean, Michael S Lawlor, Dominique Limprevil-Divers, Maria G Montez, Julia T Rushing, Adam G Tsai, David F Williamson, Ping Zhang, Judy L Bahnson, Mark A Espeland, Mary Evans, Barbara Harrison, Xavier Pi-Sunyer, Lynne E Wagenknecht, Rena R Wing, Barbara J Maschak-Carey, Marsha Miller, Brenda Montgomery, Judy L Bahnson, Paula Bolin, Kathy M Dotson, Caitlin Egan, Mary Evans, Molly Gee, Siran Ghazarian, Valerie Goldman, Carolyn Gresham, Barbara Harrison, Diane Hirsch, Amelia Hodges, Sharon D Jackson, Tina Killean, Helen Lambeth, Dominique Limprevil-Divers, Maria G Montez, Moana Mosby, Anne Murillo, Jennifer Patricio, Rebecca Reeves, Tricia Skarphol, Allison Strate, Lee Swartz, Sheikilya Thomas, Carolyn Thorson, Jacqueline Wesche-Thobaben, Carrie C Williams, Rena R Wing, Jeanne M Clark, Donna H Ryan, Mark A Espeland, Edward W Gregg, Amelia Hodges, Van S Hubbard, Karen C Johnson, Steven E Kahn, Abbas E Kitabchi, William C Knowler, Dominique Limprevil-Divers, David M Nathan, Xavier Pi-Sunyer, Monika Safford, Lynne E Wagenknecht, Carrie C Williams, Rena R Wing, Susan Z Yanovski, Jennifer Patricio, Lynne Lichtermann, Jennifer Arceneaux, Jeanne Charleston, Kathy M Dotson, Caitlin Egan, Mary Evans, Richard Foushee, Molly Gee, Carolyn Gresham, Nancy J Hall, Ruby Johnson, Robert Knopp, Helen Lambeth, Rebecca Reeves, Richard Rubin, Allison Strate, Brent Van Dorsten, Frederick L Brancati, David Kelly, Judy L Bahnson, Alain G Bertoni, Lawton S Cooper, Jeffrey M Curtis, Sarah A Gaussoin, Siran Ghazarian, Van S Hubbard, Steven E Kahn, Barbara J Maschak-Carey, Anne Murillo, Anne Peters, Xavier Pi-Sunyer, Susan Z Yanovski, Rena R Wing, Xavier Pi-Sunyer, Frederick L Brancati, George A Bray, Jeanne M Clark, Jeffrey M Curtis, Mark A Espeland, Mary Evans, John P Foreyt, Steven Haffner, Barabara Harrison, Helen P Hazuda, James O Hill, Edward S Horton, John M, Robert W Jeffery, Karen C Johnson, Steven E Kahn, David Kelly, Abbas E Kitabchi, William C Knowler, Cora E Lewis, David M Nathan, Anne Peters, Thomas A Wadden, Lynne E Wagenknecht, Thomas A Wadden, Delia S West, John P Bantle, Robert I Berkowitz, Paula Bolin, Barbara Cerniauskas, Linda Delahanty, Kathy M Dotson, Mary Evans, John P Foreyt, Edward W Gregg, Helen P Hazuda, John M Jakicic, Shiriki Kumanyika, Marsha Miller, Carmen Pal, Rebecca Reeves, Jack Rejeski, Amy D Rickman, Mara Vitolins, Don Williamson, Rena R Wing, Susan Z Yanovski
Abstract
Aims/hypothesis: Both obesity and genetics contribute to cardiovascular disease (CVD). We examined whether a genetic risk score (GRS) prospectively predicted cardiovascular morbidity and mortality among overweight/obese individuals with type 2 diabetes and whether behavioural weight loss could diminish this association.
Methods: Look AHEAD (Action for Health in Diabetes) is a randomised controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes among overweight/obese individuals with type 2 diabetes. Of the participants, 4,016 provided consent for genetic analyses and had DNA samples passing quality control procedures. These secondary data analyses focused on whether a GRS derived from 153 single nucleotide polymorphisms (SNPs) associated with coronary artery disease in the most recent genome-wide association study predicted cardiovascular morbidity and mortality over a median of 9.6 years of follow-up, and whether ILI would diminish this association.
Results: The GRS significantly predicted the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalisation for angina in the full sample (HR, 95% CI per 1 SD increase in GRS: 1.19 [1.10, 1.28]) and among individuals with no known history of CVD at baseline (HR 1.18 [95% CI 1.07, 1.30]). In no case did ILI significantly alter this association.
Conclusions/interpretation: A GRS comprised of SNPs significantly predicts cardiovascular morbidity and mortality over 9.6 years of follow-up in Look AHEAD. Lifestyle intervention did not alter the genetic association.
Clinical trial registration: NCT00017953; NCT01270763.
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Source: PubMed