title: Mechanisms of type 2 diabetes resolution after Roux-en-Y gastric bypass.
abstract: BACKGROUND
  Bariatric surgery is the most effective treatment for the reduction of weight and resolution of type 2 diabetes mellitus (T2 DM). The objective of this study was to longitudinally assess hormonal and tissue responses after RYGB.
  
  
  METHODS
  Eight patients (5 with T2 DM) were studied before and after RYGB. A standardized test meal (STM) was administered before and at 1, 3, 6, 9, 12, and 15 months. Separately, a 2-hour hyperinsulinemic-euglycemic clamp (E-clamp) and a 2-hour hyperglycemic clamp (H-clamp) were performed before and at 1, 3, 6, and 12 months. Glucagon-like peptide-1 (GLP-1) was infused during the last hour of the H-clamp. Body composition was assessed with DXA methodology.
  
  
  RESULTS
  Enrollment body mass index was 49±3 kg/m(2) (X±SE). STM glucose and insulin responses were normalized by 3 and 6 months. GLP-1 level increased dramatically at 1, 3, and 6 months, normalizing by 12 and 15 months. Insulin sensitivity (M of E-clamp) increased progressively at 3-12 months as fat mass decreased. The insulin response to glucose alone fell progressively over 12 months but the glucose clearance/metabolism (M of H-clamp) did not change significantly until 12 months. In response to GLP-1 infusion, insulin levels fell progressively throughout the 12 months.
  
  
  CONCLUSIONS
  The early hypersecretion of GLP-1 leads to hyperinsulinemia and early normalization of glucose levels. The GLP-1 response normalizes within 1 year after surgery. Enhanced peripheral tissue sensitivity to insulin starts at 3 months and is associated with fat mass loss. β-cell sensitivity improves at 12 months and after the loss of ≈33% of excess weight. There is a tightly controlled feedback loop between peripheral tissue sensitivity and β-cell and L-cell (GLP-1) responses.
authors.affiliation: Cardiovascular Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: dariush.elahi@iconplc.com.
authors.forename: Dariush
authors.initials: D
authors.lastname: Elahi
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Panagis
authors.initials: P
authors.lastname: Galiatsatos
authors.affiliation: Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Atoosa
authors.initials: A
authors.lastname: Rabiee
authors.affiliation: Department of Medicine, Lawrence Hospital, Westchester, New York.
authors.forename: Rocio
authors.initials: R
authors.lastname: Salas-Carrillo
authors.affiliation: Cardiovascular Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Amin
authors.initials: A
authors.lastname: Vakilipour
authors.affiliation: Diabetes Section, Clinical Laboratory of Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Olga D
authors.initials: OD
authors.lastname: Carlson
authors.affiliation: Cardiovascular Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Franca S
authors.initials: FS
authors.lastname: Angeli
authors.affiliation: Cardiovascular Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Shannon
authors.affiliation: Diabetes Section, Clinical Laboratory of Investigation, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Dana K
authors.initials: DK
authors.lastname: Andersen
mesh_terms: D015502:Absorptiometry, Photon; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015390:Gastric Bypass / Q000379:methods*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000601:surgery*; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: Hyperglycemic clamp; Hyperinsulinemic-euglycemic clamp; RYGB; Standardized test meal; Type 2 diabetes mellitus