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.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Look AHEAD Research Group.doi
10.1007/s00125-015-3610-zsubject
Has Abstractpub_date
2015-08-01 00:00:00pages
1803-13issue
8eissn
0012-186Xissn
1432-0428journal_volume
58pub_type
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