Abstract

Introduction: Poor dietary quality is a well-known risk factor for diabetes and cardiovascular disease (CVD), however metabolites marking adherence to U.S. dietary guidelines are unknown. Our goal was to determine a pattern of metabolites associated with the Healthy Eating Index-2015 (HEI-2015). We hypothesize that there will be metabolites positively and negatively associated with the HEI-2015 score, including those previously linked to diabetes and CVD. Methods: Sample: 2269 adult men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study without known cardiovascular disease or diabetes. Data/specimens: Fasting serum specimens, diet and demographic questionnaires at baseline. Metabolomics: Untargeted 1 H NMR CPMG spectroscopy (600 MHz) annotated by internal and external reference data sets. Statistical analysis: Metabolome-wide association study (MWAS) using linear regression models specifying each spectral feature as the outcome in separate models, HEI-2015 score as the predictor, and adjustment for age, sex, race, and study site, accounting for multiple comparisons. Elastic net regularized regression was used to select an optimal subset of features associated with HEI-2015 score. Separately, hierarchical clustering defined discrete groups of correlated NMR features also tested for association with HEI-2015 score. Results: MWAS identified 1914 spectral features significantly associated with the HEI-2015 diet score. After elastic net regression, 35 metabolomic spectral features remained associated with HEI-2015 diet score. Cluster analysis identified seven clusters, three of which were significantly associated with HEI-2015 score after Bonferroni correction. (Table) Conclusions: Cholesterol moieties, proline betaine, proline/glutamate and fatty acyls chains were significantly associated with higher diet quality in the MESA cohort. Further analysis may clarify the link between dietary quality, metabolites, and pathogenesis of diabetes and CVD.

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