title: Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations.
abstract: BACKGROUND
  Bile acids and fibroblast growth factor 19 (FGF19) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB).
  
  
  OBJECTIVE
  To describe fasting and postprandial state total bile acid (TBA) and FGF19 concentrations before and after RYGB and relate them to parameters of glucose metabolism, glucagon-like peptide-1, cholecystokinin, and cholesterol fractions.
  
  
  METHODS
  A prospective descriptive study was performed at the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
  
  
  METHODS
  Thirteen type 2 diabetic (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study.
  
  
  METHODS
  A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB.
  
  
  METHODS
  We measured fasting and postprandial TBA and FGF19 concentrations.
  
  
  RESULTS
  Fasting TBA concentrations decreased in NGT subjects (P < .001) and were unchanged in T2D patients 1 week after surgery, but then increased gradually in both groups with time from surgery (ANOVA Ptime < .001). Area under the curve (AUC) TBA was decreased in NGT subjects 1 week after RYGB (before surgery, 567 mmol * min/L [interquartile range, 481-826]; 1 wk, 419 [381-508]; P = .009) and was unchanged in T2D patients (894 [573-1002]; 695 [349-1147]; P = .97) but then increased with time from surgery in both groups (Ptime < .001). Fasting FGF19 concentrations were unchanged acutely after RYGB (NGT, 140 pg/mL [100-162], 134 [119-204], P = .42; T2D, 162 [130-196], 154 [104-164], P = .68) and remained unchanged throughout the follow-up period. AUC FGF19 increased gradually with time after surgery (Ptime < .001), resembling the changes seen with AUC TBA. One week after RYGB, glucose metabolism improved, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol decreased, and cholecystokinin and glucagon-like peptide-1 secretion increased, whereas FFA concentrations were unchanged.
  
  
  CONCLUSIONS
  TBA and FGF19 do not explain acute changes in glucose metabolism, cholesterol fractions, and gut hormone secretion after RYGB.
authors.affiliation: Departments of Endocrinology (N.B.J., C.D., K.N.B.-M., S.M.) and Surgery (V.B.K.), Hvidovre Hospital, DK-2650 Hvidovre, Denmark; Diabetes and Obesity Biology (B.S.W., T.R.C.), Novo Nordisk A/S, DK-2760 Måløv, Denmark; Sorbonne Universités (D.R., L.H.), UMPC Univ Paris 06, INSERM ERL 1157, CNRS UMR 7203 LBM, CHU St-Antoine, F-75012 Paris, France; Department of Clinical Biochemistry (J.F.R.), Rigshospitalet, University of Copenhagen, DK-2100 Copenhagen, Denmark; and Novo Nordisk Foundation Center for Basic Metabolic Research (J.J.H.), Department of Biomedical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Nils B
authors.initials: NB
authors.lastname: Jørgensen
authors.forename: Carsten
authors.initials: C
authors.lastname: Dirksen
authors.forename: Kirstine N
authors.initials: KN
authors.lastname: Bojsen-Møller
authors.forename: Viggo B
authors.initials: VB
authors.lastname: Kristiansen
authors.forename: Birgitte S
authors.initials: BS
authors.lastname: Wulff
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.forename: Lydie
authors.initials: L
authors.lastname: Humbert
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.forename: Trine R
authors.initials: TR
authors.lastname: Clausen
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D005500:Follow-Up Studies; D015390:Gastric Bypass; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery*; D015854:Up-Regulation
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors