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

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 JefferySteven 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, Holly Wyatt, The Look AHEAD Research Group

Research output: Contribution to journalArticle

13 Scopus citations

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

Keywords

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

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    McCaffery, J. M., Anderson, A., Bantle, J. P., Berkowitz, R. I., Bray, G. A., Cheskin, L., Clark, J. M., Curtis, J. M., Delahanty, L. M., Evans, M., Foreyt, J. P., Glasser, S., Gregg, E. W., Hanson, R. L., Hazuda, H. P., Hill, J. O., Horton, E. S., Huggins, G. S., Jakicic, J. M., ... The Look AHEAD Research Group (2015). 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. Diabetologia, 58(8), 1803-1813. https://doi.org/10.1007/s00125-015-3610-z