Nils B Jørgensen1, Carsten Dirksen, Kirstine N Bojsen-Møller, Viggo B Kristiansen, Birgitte S Wulff, Dominique Rainteau, Lydie Humbert, Jens F Rehfeld, Jens J Holst, Sten Madsbad, Trine R Clausen. 1. 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.
Abstract
CONTEXT: 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. DESIGN AND SETTING: A prospective descriptive study was performed at the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. PATIENTS: Thirteen type 2 diabetic (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study. INTERVENTION: A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB. MAIN OUTCOME MEASURES: 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. CONCLUSION: TBA and FGF19 do not explain acute changes in glucose metabolism, cholesterol fractions, and gut hormone secretion after RYGB.
CONTEXT: 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. DESIGN AND SETTING: A prospective descriptive study was performed at the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. PATIENTS: Thirteen type 2 diabetic (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study. INTERVENTION: A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB. MAIN OUTCOME MEASURES: 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. CONCLUSION:TBA and FGF19 do not explain acute changes in glucose metabolism, cholesterol fractions, and gut hormone secretion after RYGB.
Authors: M S Svane; N B Jørgensen; K N Bojsen-Møller; C Dirksen; S Nielsen; V B Kristiansen; S Toräng; N J Wewer Albrechtsen; J F Rehfeld; B Hartmann; S Madsbad; J J Holst Journal: Int J Obes (Lond) Date: 2016-08-30 Impact factor: 5.095
Authors: Fernanda R Azevedo; Sergio Santoro; Maria L Correa-Giannella; Marcos T Toyoshima; Daniel Giannella-Neto; Daniela Calderaro; Danielle M Gualandro; Pai C Yu; Bruno Caramelli Journal: Obes Surg Date: 2018-10 Impact factor: 4.129
Authors: Christopher M Mulla; Allison B Goldfine; Jonathan M Dreyfuss; Sander Houten; Hui Pan; David M Pober; Nicolai J Wewer Albrechtsen; Maria S Svane; Julie B Schmidt; Jens Juul Holst; Colleen M Craig; Tracey L McLaughlin; Mary-Elizabeth Patti Journal: Obes Surg Date: 2019-07 Impact factor: 4.129
Authors: V Spinelli; F Lalloyer; G Baud; E Osto; M Kouach; M Daoudi; E Vallez; V Raverdy; J-F Goossens; A Descat; P Doytcheva; T Hubert; T A Lutz; S Lestavel; B Staels; F Pattou; A Tailleux Journal: Int J Obes (Lond) Date: 2016-03-22 Impact factor: 5.095