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

The Look AHEAD Research Group

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1803-1813
Number of pages11
JournalDiabetologia
Volume58
Issue number8
DOIs
StatePublished - Aug 23 2015

Fingerprint

Type 2 Diabetes Mellitus
Life Style
Randomized Controlled Trials
Morbidity
Mortality
Health
Single Nucleotide Polymorphism
Weight Loss
Cardiovascular Diseases
Genome-Wide Association Study
Quality Control
Coronary Artery Disease
Cause of Death
Hospitalization
Obesity
Stroke
Myocardial Infarction
Clinical Trials
Education
DNA

Keywords

  • Cardiovascular disease
  • Genetics
  • Lifestyle intervention
  • Myocardial infarction
  • Obesity
  • Stroke
  • Type 2 diabetes
  • Weight loss

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{0ccc15eb2ae64e63a64a10780be08c83,
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 Hazuda, {Helen P} 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 Wadden, {Thomas A.} and Wagenknecht, {Lynne E.} and Wing, {Rena R.} and Holly Wyatt",
year = "2015",
month = "8",
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",

}

TY - JOUR

T1 - Prospective association of a genetic risk score and lifestyle intervention with cardiovascular morbidity and mortality among individuals with type 2 diabetes

T2 - the Look AHEAD randomised controlled trial

AU - The Look AHEAD Research Group

AU - McCaffery, Jeanne M.

AU - Anderson, Andrea

AU - Bantle, John P.

AU - Berkowitz, Robert I.

AU - Bray, George A.

AU - Cheskin, Lawrence

AU - Clark, Jeanne M.

AU - Curtis, Jeffrey M.

AU - Delahanty, Linda M.

AU - Evans, Mary

AU - Foreyt, John P.

AU - Glasser, Stephen

AU - Gregg, Edward W.

AU - Hanson, Robert L.

AU - Hazuda, Helen P.

AU - Hazuda, Helen P

AU - Horton, Edward S.

AU - Huggins, Gordon S.

AU - Jakicic, John M.

AU - Jeffery, Robert W.

AU - Johnson, Karen C.

AU - Kahn, Steven E.

AU - Kelley, David E.

AU - Kitabchi, Abbas E.

AU - Knowler, William C.

AU - Lewis, Cora E.

AU - Montez, Maria G.

AU - Kure, Anne

AU - Nathan, David M.

AU - Nyenwe, Ebenezer

AU - Pajewski, Nicholas M.

AU - Papandonatos, George D.

AU - Patricio, Jennifer

AU - Peter, Inga

AU - Peters, Anne

AU - Pi-Sunyer, Xavier

AU - Pownall, Henry

AU - Wadden, Thomas A.

AU - Wagenknecht, Lynne E.

AU - Wing, Rena R.

AU - Wyatt, Holly

PY - 2015/8/23

Y1 - 2015/8/23

N2 - 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.

AB - 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.

KW - Cardiovascular disease

KW - Genetics

KW - Lifestyle intervention

KW - Myocardial infarction

KW - Obesity

KW - Stroke

KW - Type 2 diabetes

KW - Weight loss

UR - http://www.scopus.com/inward/record.url?scp=84937526810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937526810&partnerID=8YFLogxK

U2 - 10.1007/s00125-015-3610-z

DO - 10.1007/s00125-015-3610-z

M3 - Article

VL - 58

SP - 1803

EP - 1813

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 8

ER -