Associations of Diabetes Mellitus, Insulin, Leptin, and Ghrelin With Gastroesophageal Reflux and Barrett's Esophagus

Background & Aims Insulin and leptin have proliferative and anti-apoptotic effects. Ghrelin promotes gastric emptying and secretion of growth hormone and inhibits inflammation. We assessed whether diabetes mellitus and serum levels of insulin, leptin, and ghrelin are associated with gastroesopha...

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Published in:	Gastroenterology (New York, N.Y. 1943) Vol. 145; no. 6; pp. 1237 - 1244.e5
Main Authors:	Rubenstein, Joel H, Morgenstern, Hal, McConell, Daniel, Scheiman, James M, Schoenfeld, Philip, Appelman, Henry, McMahon, Laurence F, Kao, John Y, Metko, Val, Zhang, Min, Inadomi, John M
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-12-2013
Subjects:	Aged Barrett Esophagus - blood Barrett Esophagus - diagnosis Barrett Esophagus - epidemiology Case-Control Studies Diabetes Complications - blood Diabetes Complications - complications Endoscopy, Gastrointestinal Gastroenterology and Hepatology Gastroesophageal Reflux Gastroesophageal Reflux - blood Gastroesophageal Reflux - diagnosis Gastroesophageal Reflux - epidemiology Ghrelin Ghrelin - blood Humans Incidence Insulin Insulin - blood Leptin Leptin - blood Logistic Models Male Middle Aged Risk Factors BE colorectal cancer OR CI PPI Gastroesophageal Reflux odds ratio Insulin proton pump inhibitor GERD Ghrelin CRC LA Leptin Barrett's esophagus confidence interval Los Angeles gastroesophageal reflux disease
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Summary:	Background & Aims Insulin and leptin have proliferative and anti-apoptotic effects. Ghrelin promotes gastric emptying and secretion of growth hormone and inhibits inflammation. We assessed whether diabetes mellitus and serum levels of insulin, leptin, and ghrelin are associated with gastroesophageal reflux disease (GERD) and Barrett's esophagus. Methods We conducted a case-control study in 822 men undergoing colorectal cancer screening who were recruited to also undergo upper endoscopy. We identified 70 with Barrett's esophagus; 80 additional men with Barrett's esophagus were recruited shortly after their clinical diagnoses. Serum levels of insulin, leptin, and ghrelin were assayed in all 104 fasting men with Barrett's esophagus without diabetes and 271 without diabetes or Barrett's esophagus. Logistic regression was used to estimate the effects of diabetes and levels of insulin, leptin, and ghrelin on GERD and Barrett's esophagus. Results Among men with GERD, diabetes was inversely associated with Barrett's esophagus (adjusted odds ratio [OR] = 0.383; 95% confidence interval [CI]: 0.179−0.821). Among nondiabetics, hyperinsulinemia was positively associated with Barrett's esophagus, but the association was attenuated by adjustment for leptin and ghrelin. Leptin was positively associated with Barrett's esophagus, adjusting for obesity, GERD, and levels of insulin and ghrelin (OR for 3rd vs 1st tertile = 3.25; 95% CI: 1.29−8.17); this association was stronger in men with GERD ( P = .01 for OR heterogeneity). Ghrelin was positively associated with Barrett's esophagus (OR for an increment of 400 pg/mL = 1.39; 95% CI: 1.09−1.76), but inversely associated with GERD (OR for 3rd vs 1st tertile = 0.364; 95% CI: 0.195−0.680). Conclusions Based on a case-control study, leptin was associated with Barrett's esophagus, particularly in men with GERD. Serum insulin level was associated with Barrett's esophagus, but might be mediated by leptin. Serum ghrelin was inversely associated with GERD, as hypothesized, but positively associated with Barrett's esophagus, contrary to our hypothesis. Additional studies are needed in men and women to replicate these findings.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0016-5085 1528-0012
DOI:	10.1053/j.gastro.2013.08.052