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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.

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    Source

    Diabetologia 58:8 2015 Aug pg 1803-13

    MeSH

    Aged
    Body Mass Index
    Cardiovascular Diseases
    Diabetes Mellitus, Type 2
    Female
    Genetic Predisposition to Disease
    Humans
    Life Style
    Male
    Middle Aged
    Obesity
    Polymorphism, Single Nucleotide
    Prospective Studies
    Treatment Outcome
    Weight Loss

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, N.I.H., Intramural
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    25972230

    Citation

    Look AHEAD Research Group. "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, vol. 58, no. 8, 2015, pp. 1803-13.
    Look AHEAD Research Group. 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. 2015;58(8):1803-13.
    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), pp. 1803-13. doi:10.1007/s00125-015-3610-z.
    Look AHEAD Research Group. 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. 2015;58(8):1803-13. PubMed PMID: 25972230.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. A1 - ,, Y1 - 2015/05/14/ PY - 2014/11/18/received PY - 2015/04/07/accepted PY - 2015/5/15/entrez PY - 2015/5/15/pubmed PY - 2016/4/14/medline SP - 1803 EP - 13 JF - Diabetologia JO - Diabetologia VL - 58 IS - 8 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. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/25972230/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_ L2 - https://dx.doi.org/10.1007/s00125-015-3610-z DB - PRIME DP - Unbound Medicine ER -