Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Metabolomic profiling to dissect the role of visceral fat in cardiometabolic health

OBJECTIVE: Abdominal obesity is associated with increased risk of type 2 diabetes (T2D) and cardiovascular disease. The aim of this study was to assess whether metabolomic markers of T2D and blood pressure (BP) act on these traits via visceral fat (VF) mass.

METHODS: Metabolomic profiling of 280 fasting plasma metabolites was conducted on 2,401 women from TwinsUK. The overlap was assessed between published metabolites associated with T2D, insulin resistance, or BP and those that were identified to be associated with VF (after adjustment for covariates) measured by dual-energy X-ray absorptiometry.

RESULTS: In addition to glucose, six metabolites were strongly associated with both VF mass and T2D: lactate and branched-chain amino acids, all of them related to metabolism and the tricarboxylic acid cycle; on average, 38.5% of their association with insulin resistance was mediated by their association with VF mass. Five metabolites were associated with BP and VF mass including the inflammation-associated peptide HWESASXX, the steroid hormone androstenedione, lactate, and palmitate. On average, 29% of their effect on BP was mediated by their association with VF mass.

CONCLUSIONS: Little overlap was found between the metabolites associated with BP and those associated with insulin resistance via VF mass.