title: Associations of diabetes mellitus, insulin, leptin, and ghrelin with gastroesophageal reflux and Barrett's esophagus.
abstract: OBJECTIVE
  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 3(rd) vs 1(st) 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 3(rd) vs 1(st) 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.
authors.affiliation: Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan; Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: jhr@umich.edu.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rubenstein
authors.forename: Hal
authors.initials: H
authors.lastname: Morgenstern
authors.forename: Daniel
authors.initials: D
authors.lastname: McConell
authors.forename: James M
authors.initials: JM
authors.lastname: Scheiman
authors.forename: Philip
authors.initials: P
authors.lastname: Schoenfeld
authors.forename: Henry
authors.initials: H
authors.lastname: Appelman
authors.forename: Laurence F
authors.initials: LF
authors.lastname: McMahon
authors.forename: John Y
authors.initials: JY
authors.lastname: Kao
authors.forename: Val
authors.initials: V
authors.lastname: Metko
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: John M
authors.initials: JM
authors.lastname: Inadomi
mesh_terms: D000368:Aged; D001471:Barrett Esophagus / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000097:blood / Q000150:complications*; D016099:Endoscopy, Gastrointestinal; D005764:Gastroesophageal Reflux / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D054439:Ghrelin; D007328:Insulin; D020738:Leptin
keywords: BE; Barrett's esophagus; CI; CRC; GERD; Gastroesophageal Reflux; Ghrelin; Insulin; LA; Leptin; Los Angeles; OR; PPI; colorectal cancer; confidence interval; gastroesophageal reflux disease; odds ratio; proton pump inhibitor