Serum Leptin and Adiponectin Levels and Risk of Barrett's Esophagus and Intestinal Metaplasia of the Gastroesophageal Junction

Abstract

Persons diagnosed with Barrett’s esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EA). Obesity is a major risk factor for both BE and EA. The purpose of this study was to determine the extent to which the adipokines leptin and adiponectin, both of which are deregulated in obese states, mediate the obesity-BE relationship. In this case-control study based in western Washington State, 106 male and 71 female patients newly diagnosed with BE were compared with 112 male and 64 female controls from the general population. Relationships between leptin and adiponectin, obesity, and BE were examined using unconditional logistic regression. Females in the highest tertiles of body mass index and waist circumference were at the greatest risk of BE (adjusted OR=4.3 (95% CI=1.7–10.7), Ptrend= <.01; OR=4.9 (95% CI=1. 9–12.5), Ptrend= <.01, respectively) compared to females in the lowest tertiles. Adjustment for leptin and adiponectin attenuated these associations by 43% and 41%, respectively. Similarly, males in the highest tertiles of waist circumference and waist-to-hip ratio were at the greatest risk of BE (adjusted OR=2.1 (95% CI=1.1–4.2), Ptrend=.08; OR=2.7 (95% CI=1.3–5.7), Ptrend=.01, respectively) compared to males in the lowest tertiles. However, adjustment for leptin and adiponectin attenuated these associations by only 6% and 8%, respectively. Our study results are consistent with the notion that circulating leptin and adiponectin partially mediate the obesity-BE relationship, particularly in women. Leptin and adiponectin’s role in the progression from normal epithelium to BE and on to EA should be further elucidated.

Adiponectin level changes among Egyptians with gastroesophageal reflux disease

“…Serum hypoadiponectinemia in BE was also shown in a variety of studies, such as the study by Mokrowiecka et al 18. and another one by Thompson et al .,19 and their results were similar to our study. Moreover, the study of Greer et al 20.…”

Risk factors for Barrettʼs esophagus

“…In particular, there was a strong inverse association with serum levels of the anti-inflammatory cytokine IL-10 (OR 5th vs. 1st quintile ¼ 0.14; 95% CI ¼ 0.05, 0.35), and they surprisingly found a strongly inverse association with pro-inflammatory cytokine IL-1b (OR for at least median vs. not detectable¼ 0.03; 95% CI ¼ 0.006, 0.13). Barrett's esophagus was very strongly associated with serum leptin (OR 5th vs. 1st quintile ¼ 8.02; 95% CI ¼ 2.79, 23.1), confirming the prior reports [9][10][11]. In a similar casecontrol study, leptin was strongly associated with Barrett's esophagus, but only among those with GERD (OR 3rd vs. 1st tertile ¼ 6.50; 95% CI ¼ 2.11, 20.0) and not among those without GERD (OR ¼ 1.39; 95% CI ¼ 0.393, 4.89, P-value for heterogeneity ¼ 0.01) [12 & ].…”

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

“…Adiponectin and leptin are key regulators of insulin sensitivity 43, 44 . Serum levels of leptin and adiponectin may partially account for the relationship between obesity and Barrett’s esophagus 45 , although studies have yielded inconsistent and sex-specific results 46, 47 . We did not observe sex-specific results by GERD in our study (Supplementary Table 2).…”