title: Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy.
abstract: OBJECTIVE
  Weight loss after pharmacotherapy varies greatly. We aimed to examine associations of quantitative gastrointestinal and psychological traits with obesity, and to validate the ability of these traits to predict responses of obese individuals to pharmacotherapy.
  
  
  METHODS
  In a prospective study, we measured gastric emptying of solids and liquids, fasting and postprandial gastric volume, satiation by nutrient drink test (volume to fullness and maximal tolerated volume), satiety after an ad libitum buffet meal, gastrointestinal hormones, and psychological traits in 328 normal-weight, overweight, or obese adults. We also analyzed data from 181 previously studied adults to assess associations betwecen a subset of traits with body mass index and waist circumference. Latent dimensions associated with overweight or obesity were appraised by principal component analyses. We performed a proof of concept, placebo-controlled trial of extended-release phentermine and topiramate in 24 patients to validate associations between quantitative traits and response to weight-loss therapy.
  
  
  RESULTS
  In the prospective study, obesity was associated with fasting gastric volume (P = .03), accelerated gastric emptying (P < .001 for solids and P = .011 for liquids), lower postprandial levels of peptide tyrosine tyrosine (P = .003), and higher postprandial levels of glucagon-like peptide 1 (P < .001). In a combined analysis of data from all studies, obesity was associated with higher volume to fullness (n = 509; P = .038) and satiety with abnormal waist circumference (n = 271; P = .016). Principal component analysis identified latent dimensions that accounted for approximately 81% of the variation among overweight and obese subjects, including satiety or satiation (21%), gastric motility (14%), psychological factors (13%), and gastric sensorimotor factors (11%). The combination of phentermine and topiramate caused significant weight loss, slowed gastric emptying, and decreased calorie intake; weight loss in response to phentermine and topiramate was significantly associated with calorie intake at the prior satiety test.
  
  
  CONCLUSIONS
  Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof of concept clinical trial, predicted response to pharmacotherapy for obesity. ClinicalTrials.gov Number: NCT01834404.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota. Electronic address: camilleri.michael@mayo.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Andrea
authors.initials: A
authors.lastname: Shin
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Vazquez-Roque
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Johanna
authors.initials: J
authors.lastname: Iturrino
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Jessica
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Deborah
authors.initials: D
authors.lastname: Eckert
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D000328:Adult; D000368:Aged; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D001007:Anxiety / Q000523:psychology; D001828:Body Image; D015992:Body Mass Index; D002766:Cholecystokinin / Q000097:blood; D015331:Cohort Studies; D003692:Delayed-Action Preparations; D003863:Depression / Q000523:psychology; D004151:Dipeptides / Q000097:blood*; D004338:Drug Combinations; D005215:Fasting / Q000502:physiology*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives / Q000627:therapeutic use; D005746:Gastric Emptying / Q000502:physiology*; D054439:Ghrelin / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology; D009929:Organ Size; D050177:Overweight / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D019894:Peptide YY / Q000097:blood; D010645:Phentermine / Q000627:therapeutic use; D019518:Postprandial Period / Q000502:physiology*; D025341:Principal Component Analysis; D011446:Prospective Studies; D012527:Satiation / Q000502:physiology*; D020377:Self Efficacy; D013270:Stomach / Q000473:pathology / Q000503:physiopathology*; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D003692:Delayed-Action Preparations; D004151:Dipeptides; D004338:Drug Combinations; D054439:Ghrelin; D000077236:Topiramate; C042696:tyrosyltyrosine; D019894:Peptide YY; D005632:Fructose; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D010645:Phentermine
keywords: BMI; Incretin; Phentermine; Satiety; Topiramate