@article{44696db68d7d4aafa070fa7126bec80e,
title = "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",
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.",
keywords = "Cardiovascular disease, Genetics, Lifestyle intervention, Myocardial infarction, Obesity, Stroke, Type 2 diabetes, Weight loss",
author = "{The Look Ahead Research Group} and McCaffery, {Jeanne M.} and Andrea Anderson and Bantle, {John P.} and Berkowitz, {Robert I.} and Bray, {George A.} and Lawrence Cheskin and Clark, {Jeanne M.} and Curtis, {Jeffrey M.} and Delahanty, {Linda M.} and Mary Evans and Foreyt, {John P.} and Stephen Glasser and Gregg, {Edward W.} and Hanson, {Robert L.} and Hazuda, {Helen P.} and Hill, {James O.} and Horton, {Edward S.} and Huggins, {Gordon S.} and Jakicic, {John M.} and Jeffery, {Robert W.} and Johnson, {Karen C.} and Kahn, {Steven E.} and Kelley, {David E.} and Kitabchi, {Abbas E.} and Knowler, {William C.} and Lewis, {Cora E.} and Montez, {Maria G.} and Anne Kure and Nathan, {David M.} and Ebenezer Nyenwe and Pajewski, {Nicholas M.} and Papandonatos, {George D.} and Jennifer Patricio and Inga Peter and Anne Peters and Xavier Pi-Sunyer and Henry Pownall and Pownall, {Henry J.} and Wagenknecht, {Lynne E.} and Wing, {Rena R.} and Holly Wyatt",
note = "Funding Information: Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056); the Clinical Translational Research Center (CTRC) funded by the Clinical and Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). Funding Information: Funded by the National Institutes of Health through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women{\textquoteright}s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the I.H.S. or other funding sources. Publisher Copyright: {\textcopyright} 2015, Springer-Verlag Berlin Heidelberg.",
year = "2015",
month = aug,
day = "23",
doi = "10.1007/s00125-015-3610-z",
language = "English (US)",
volume = "58",
pages = "1803--1813",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "8",
}