Abstract
BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes. OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia. METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an ∼18 y follow-up period. A metabolome-wide association study of avocado consumption status (consumer compared with nonconsumer) was conducted, and the relationship of these features with glycemia via cross-sectional associations with fasting insulin and glucose and longitudinal associations with incident T2D was examined. RESULTS: Three highly-correlated spectral features were associated with avocado intake at metabolome-wide significance levels (P < 5.3 ∗ 10(-7)) and combined into a single biomarker. We did not find evidence that these features were additionally associated with overall dietary quality, nor with any of 47 other food groups (all P > 0.001), supporting their suitability as a biomarker of avocado intake. Avocado intake showed a modest association only with lower fasting insulin (β = -0.07 (+/-) 0.03, P = 0.03), an association that was attenuated to nonsignificance when additionally controlling for body mass index (kg/m(2)). However, our biomarker of avocado intake was strongly associated with lower fasting glucose (β = -0.22 (+/-) 0.02, P < 2.0 ∗ 10(-16)), lower fasting insulin (β = -0.17 (+/-) 0.02, P < 2.0 ∗ 10(-16)), and a lower incidence of T2D (hazard ratio: 0.68; 0.63-074, P < 2.0 ∗ 10(-16)), even when adjusting for BMI. CONCLUSIONS: Highly significant associations between glycemia and avocado-related metabolomic features, which serve as biomarkers of the physiological impact of dietary intake after digestion and absorption, compared to modest relationships between glycemia and avocado consumption, highlights the importance of considering individual differences in metabolism when considering diet-health relationships.