Gastroenterology

Gastroenterology

Volume 145, Issue 6, December 2013, Pages 1237-1244.e5
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Associations of Diabetes Mellitus, Insulin, Leptin, and Ghrelin With Gastroesophageal Reflux and Barrett's Esophagus

https://doi.org/10.1053/j.gastro.2013.08.052Get rights and content

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.

Section snippets

Study Design

We conducted a case-control study of 822 male CRC screenees, aged 50−79 years, presenting for colonoscopy at either the University of Michigan Health System's East Ann Arbor Medical Procedures Center or the Ann Arbor Veterans Affairs Medical Center. We recruited the CRC screenees to undergo upper endoscopy regardless of GERD symptoms, and we prospectively classified them on the basis of BE. BE was identified in 70 men (8.5%). In addition, we recruited 80 men aged 50−79 years who had recently

Results

A total of 1308 male CRC screenees were recruited to undergo upper endoscopy, of which 1202 were eligible, and 851 were enrolled (consent rate 71%). Eight hundred and twenty-two completed the esophagogastroduodenoscopy; 29 were withdrawn from the study due to impact on the clinical throughput of the endoscopy unit (n = 12), the inability to adequately sedate for the procedures (n = 10), exclusion criteria identified after consent (n = 4), or the patient withdrawing consent (n = 3).

Compared with

Discussion

We estimated the effects of diabetes mellitus, serum insulin, leptin, and ghrelin on GERD and BE in men. We found an inverse association of ghrelin with GERD symptoms and erosive esophagitis. Insulin was associated with BE, but its effect appeared to be modified by GERD: hyperinsulinemia was positively associated with BE only among those with GERD. Leptin was also associated with BE, and its effect also appeared to be stronger among men with GERD symptoms. Contrary to our hypothesis, we found a

Acknowledgments

Brenda Vibbart assisted with administration of the grants and clerical work. Donald May, Jeffrey Cole, and Jeffrey Holden assisted with administration of the grants. We greatly appreciate the assistance of the endoscopists and staff at the University of Michigan and the Ann Arbor Veterans Affairs Medical Center for performing and assisting with the research upper endoscopies and biopsies as well as technical support from Kim Gonzalez, Sara Kitzsteiner and Russell Possley at the CLASS Laboratory.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Research and salary funding was provided for JHR by the Damon Runyon Cancer Research Foundation Gordon Family Clinical Investigator Award (CI: 36-07). JMS was supported by a Senior Mentoring Grant from the American Society for Gastrointestinal Endoscopy. JMI was supported by grant number K24 DK080941, and JYK was supported by grant number R01DK087708, both from the National Institute of Diabetes and Digestive and Kidney Diseases. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other funding sources.

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