Adiponectin May Modify the Risk of Barrett’s Esophagus in Patients With Gastroesophageal Reflux Disease

Abstract

Background & Aims Abdominal obesity and increasing body mass index are risk factors for esophageal adenocarcinoma and its main precursor, Barrett’s esophagus; however, there are no known biological mechanisms for these associations or regarding why only some patients with gastroesophageal reflux disease develop Barrett’s esophagus. We evaluated the association between Barrett’s esophagus and multimers of an adipose-associated hormone, adiponectin. Methods We conducted a case-control study evaluating the associations between adiponectin (total, high molecular weight, and low/medium molecular weight) and Barrett’s esophagus within the Kaiser Permanente Northern California population. Patients with a new diagnosis of Barrett’s esophagus (cases) were matched to patients with gastroesophageal reflux disease (GERD) without Barrett’s esophagus and to population controls. Results Complete serologic and epidemiologic data were available for 284 cases, 294 GERD controls, and 285 population controls. Increasing adiponectin levels were a risk factor for Barrett’s esophagus among patients with gastroesophageal reflux disease (total adiponectin fourth vs. first quartile odds ratio [OR]=1.96; 95% confidence interval (CI) 1.17–3.27; high molecular weight adiponectin OR=1.65; 95% CI 1.00–2.73; low/medium molecular weight adiponectin OR=2.18; 95% CI 1.33–3.56, but not compared with population controls. The associations were significantly stronger among patients reporting frequent GERD symptoms and among smokers (p-values interaction <0.01). Conclusion Adiponectin levels are positively associated with the risk of Barrett’s esophagus among patients with GERD and among smokers, but not among population controls without GERD symptoms. Higher adiponectin concentrations may either independently contribute to the aberrant healing of esophageal injury into Barrett’s esophagus or be a marker for other factors.

Association of Serum Levels of Adipokines and Insulin With Risk of Barrett's Esophagus: A Systematic Review and Meta-Analysis

“…26–34 There were 10 cohorts in the 9 studies included in the analysis because 1 of the studies had a pilot and a validation cohort. Two studies 40,41 were excluded from quantitative analysis because they reported only unadjusted values and another study 42 was excluded because data were only available on gastric leptin levels.…”

“…Thompson et al 34 also used population control subjects who were selected by random digit dialing. Almers et al 26 used 2 control groups, a GERD control group that had an International Classification of Diseases-9 diagnosis of GERD and an upper endoscopy showing absence of columnar meta-plasia; the second population control group consisted of persons having a Kaiser Permanente membership and were randomly selected using risk set sampling. All included studies were at low risk of bias.…”

“…All but 1 study included both incident and prevalent cases of BE; the study by Almers et al 26 included only newly diagnosed BE cases. Average BMI was 29.6 ± 7 kg/m 2 (BMI was reported as means and standard deviation in 6 studies).…”

“…Several observational studies have examined the association of serum adipokines and insulin with BE 26–34 but evidence regarding this association remains inconclusive. Given the uncertainty around the overall body of evidence, we decided to conduct a systematic review and meta-analysis of observational studies evaluating the relationship between circulating levels of adiponectin, leptin, and insulin, and the risk of BE.…”

Adiponectin level changes among Egyptians with gastroesophageal reflux disease

“…The observed associations of adiponectin with BE remained significant after adjustment of potential confounders such as age, gender, race, and obesity state, suggesting that this adipokine is associated strongly with BE and may play a biological role in the pathogenesis of esophageal columnar metaplasia. Contrary to our study, Almers et al 21. conducted a case–control study evaluating the association between adiponectin (total, high, and low/medium molecular weight) and BE in the Kaiser Permanente Northern California population.…”