Volume 145, Issue 6, Pages 1237-1244.e5 (December 2013) Associations of Diabetes Mellitus, Insulin, Leptin, and Ghrelin With Gastroesophageal Reflux and Barrett's Esophagus  Joel H. Rubenstein, Hal Morgenstern, Daniel McConell, James M. Scheiman, Philip Schoenfeld, Henry Appelman, Laurence F. McMahon, John Y. Kao, Val Metko, Min Zhang, John M. Inadomi  Gastroenterology  Volume 145, Issue 6, Pages 1237-1244.e5 (December 2013) DOI: 10.1053/j.gastro.2013.08.052 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 Potential mechanisms of association of obesity with BE. Obesity mechanically promotes GERD, which can lead to BE. Obesity also leads to insulin resistance and leptin resistance, manifesting as elevated circulating levels of insulin and leptin. Leptin and/or insulin might promote BE, but could also be confounded by the effects of the other. Additionally, the effects of insulin might be mediated through leptin because hyperinsulinemia promotes leptin secretion. We had also hypothesized that diabetes mellitus would be associated with BE due to long-standing hyperinsulinemia. However, in this study, the effect of insulin appeared to be confounded by leptin and ghrelin, and diabetes appeared to be inversely associated with BE. Ghrelin promotes gastric emptying, and so could inhibit GERD. Ghrelin also promotes secretion of growth hormone, which might promote healing of erosive esophagitis with Barrett's metaplasia, either directly, or mediated through local production of insulin-like growth factor-1 (IGF-1). Gastroenterology 2013 145, 1237-1244.e5DOI: (10.1053/j.gastro.2013.08.052) Copyright © 2013 AGA Institute Terms and Conditions