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/m²). 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.

Background

Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

Objective

To identify whether any metabolites associated with red meat intake are also associated with inflammation.

Methods

A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, homocysteine, and tumor necrosis factor alpha, and untargeted proton nuclear magnetic resonance (¹H NMR) metabolomic features. Associations between these variables were examined using linear regression models, adjusted for demographic factors, lifestyle behaviors, and body mass index (BMI).

Results

In analyses that adjust for BMI, neither processed nor unprocessed forms of red meat were associated with any markers of inflammation (all P > 0.01). However, when adjusting for BMI, unprocessed red meat was inversely associated with spectral features representing the metabolite glutamine (sentinel hit: β = -0.09 ± 0.02, P = 2.0 × 10^-5), an amino acid which was also inversely associated with CRP level (β = -0.11 ± 0.01, P = 3.3 × 10^-10).

Conclusions

Our analyses were unable to support a relationship between either processed or unprocessed red meat and inflammation, over and above any confounding by BMI. Glutamine, a plasma correlate of lower unprocessed red meat intake, was associated with lower CRP levels. The differences in diet-inflammation associations, compared with diet metabolite-inflammation associations, warrant further investigation to understand the extent that these arise from the following: 1) a reduction in measurement error with metabolite measures; 2) the extent that which factors other than unprocessed red meat intake contribute to glutamine levels; and 3) the ability of plasma metabolites to capture individual differences in how food intake is metabolized.

Background and aims

To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry.

Methods and results

The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%β), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status. In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (β = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; β = -0.36 ± 0.21, P = 0.02), and lower fasting glucose (β = -0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%β (β = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (β = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (β = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes.

Conclusions

We observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry.

Article highlights

We aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.