title: Postprandial metabolite profiles reveal differential nutrient handling after bariatric surgery compared with matched caloric restriction.
abstract: BACKGROUND
  Roux-en-Y gastric bypass (RYGB) surgery results in exaggerated postprandial insulin and incretin responses and increased susceptibility to hypoglycemia.
  
  
  OBJECTIVE
  We examined whether these features are due to caloric restriction (CR) or altered nutrient handling.
  
  
  METHODS
  We performed comprehensive analysis of postprandial metabolite responses during a 2-hour mixed-meal tolerance (MMT) test in 20 morbidly obese subjects with type 2 diabetes who underwent RYGB surgery or matched CR. Acylcarnitines and amino acids (AAs) were measured using targeted mass spectrometry. A linear mixed model was used to determine the main effect of interventions and interaction term to assess the effect of interventions on postprandial kinetics.
  
  
  RESULTS
  Two weeks after these interventions, several gut hormones (insulin, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide 1), glucose, and multiple AAs, including branched-chain and aromatic species, exhibited a more rapid rate of appearance and clearance in RYGB surgery subjects than in CR subjects during the MMT test. In the RYGB surgery group, changes in leucine/isoleucine, methionine, phenylalanine, and glucagon-like peptide 1 response were associated with changes in insulin response. Levels of alanine, pyruvate, and lactate decreased significantly at the later stages of meal challenge in RYGB surgery subjects but increased with CR.
  
  
  CONCLUSIONS
  RYGB surgery results in improved metabolic flexibility (ie, greater disposal of glucose and AAs and more complete β-oxidation of fatty acids) compared with CR. The changes in the AA kinetics may augment the hormonal responses seen after RYGB surgery. The reduction in key gluconeogenic substrates in the postprandial state may contribute to increased susceptibility to hypoglycemic symptoms in RYGB surgery subjects.
authors.affiliation: *Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC †Department of Medicine, National University Health System, Singapore and Departments of ‡Medicine §General Surgery ¶Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC.
authors.forename: Chin Meng
authors.initials: CM
authors.lastname: Khoo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Muehlbauer
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stevens
authors.forename: Zehra
authors.initials: Z
authors.lastname: Pamuklar
authors.forename: Jiegen
authors.initials: J
authors.lastname: Chen
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.forename: Alfonso
authors.initials: A
authors.lastname: Torquati
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000601:surgery*; D005260:Female; D015390:Gastric Bypass / Q000379:methods; D005768:Gastrointestinal Hormones / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000097:blood; D010535:Laparoscopy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000601:surgery*; D011183:Postoperative Complications / Q000097:blood; D019518:Postprandial Period / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007328:Insulin