Metabolic Syndrome Increases Risk of Barrett Esophagus in the Absence of Gastroesophageal Reflux

Abstract

GOALS: Evaluate the association between metabolic syndrome (MetS) and risk of Barrett’s esophagus (BE) using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database compared with two control groups—Medicare population controls and endoscopy controls. BACKGROUND: Barrett’s esophagus principally arises as an adaptation to the proinflammatory state induced by gastroesophageal reflux disease (GERD). The relationship between obesity and BE is presumed to be mediated by GERD. However, evidence suggests central adiposity also increases risk of BE independent of GERD. Central adiposity is one risk factor defining metabolic syndrome, which confers a systemic proinflammatory state—a potential GERD-independent mechanism by which obesity could increase risk of BE. STUDY: MetS was defined as diagnosis of at least three of the following conditions: obesity, elevated triglycerides, high blood pressure, and elevated fasting glucose. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: In 2,198 incident BE cases, prior MetS was significantly associated with BE [OR 1.20; 95%CI 1.07, 1.36] compared with population controls. However, GERD status modified the association; among those without prior GERD, MetS increased risk of BE by 34%, however no association was observed among those with a prior GERD diagnosis (p-value for effect modification <0.001). MetS was not associated with risk of BE compared with endoscopy controls. CONCLUSIONS: MetS increased risk of BE compared with population controls, an association driven by and confined to the non-GERD stratum. MetS may mediate an association between central adiposity and BE for those without GERD.

Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma

“…The metabolic syndrome has been associated with Barrett’s esophagus and EAC. 28, 29 However, the evidence for an association between hyperinsulinemia or diabetes mellitus with Barrett’s esophagus or EAC has been inconsistent. 27, 30–35 …”

Metabolic syndrome in relation to Barrett⿿s esophagus and esophageal adenocarcinoma: Results from a large population-based case-control study in the Clinical Practice Research Datalink

“…HDL cholesterol was not specified in the CPRD data and thus lowered HDL cholesterol was not used in our definition of MetS. This approach is similar to analyses conducted in SEER-Medicare data, which also does not capture lowered HDL cholesterol 18 . A subject was considered exposed to either high cholesterol or hypertension if he or she received both a diagnostic READ code for the condition and a prescription for an appropriate medication.…”

“…The proinflammatory effects of excess adipose tissue are a hallmark of MetS 12 , which itself is a cluster of metabolic disorders that includes abdominal obesity, hypertension, lowered high density lipoprotein (HDL) cholesterol, elevated triglycerides, and elevated fasting glucose 13 . MetS is a better predictor of total mortality than its individual components 14 , and may increase the risk of BE 15–18 and EA 19 .…”

“…We recently demonstrated that MetS increased risks of BE 18 and EA 1 in an older-aged US population (SEER-Medicare), associations driven by and confined to those without a history of GERD. We proposed that in those without symptomatic GERD, systemic inflammation—represented by MetS—increases the risk for normal esophageal tissues to develop metaplasia and eventually cancer.…”

“…The few studies that have evaluated the association of MetS in relation to BE or EA have either not been population-based 15–17 , did not include the full age-range of patients 18 or did not investigate potential effect-modification by GERD 19–21 . Therefore, using data collected prospectively in the Clinical Practice Research Datalink (CPRD), which contains longitudinal medical records of virtually all UK primary care events of >8 million subjects of all ages, we investigated MetS in relation to risks of BE and EA separately and evaluated whether GERD was an effect-modifier of these relationships.…”