Jørgensen Nils B, Dirksen Carsten, Bojsen-Møller Kirstine N, Kristiansen Viggo B, Wulff Birgitte S, Rainteau Dominique, Humbert Lydie, Rehfeld Jens F, Holst Jens J, Madsbad Sten, Clausen Trine R
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.
J Clin Endocrinol Metab. 2015 Mar;100(3):E396-406. doi: 10.1210/jc.2014-1658. Epub 2014 Dec 23.
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).
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.
A prospective descriptive study was performed at the Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
Thirteen type 2 diabetic (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study.
A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB.
We measured fasting and postprandial TBA and FGF19 concentrations.
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.
TBA and FGF19 do not explain acute changes in glucose metabolism, cholesterol fractions, and gut hormone secretion after RYGB.
胆汁酸和成纤维细胞生长因子19（FGF19）被认为是Roux-en-Y胃旁路术（RYGB）后葡萄糖代谢改善的关键介质。
描述RYGB前后空腹和餐后状态下总胆汁酸（TBA）和FGF19的浓度，并将它们与葡萄糖代谢、胰高血糖素样肽-1、胆囊收缩素和胆固醇组分的参数相关联。
在丹麦霍伊勒夫市霍伊勒夫医院内分泌科进行了一项前瞻性描述性研究。
13名2型糖尿病（T2D）患者和12名糖耐量正常（NGT）受试者参与了该研究。
在RYGB前以及术后1周、3个月和1年进行了4小时流食试验。
我们测量了空腹和餐后TBA和FGF19的浓度。
NGT受试者的空腹TBA浓度降低（P <.001），T2D患者术后1周未发生变化，但两组均随术后时间逐渐升高（方差分析Ptime <.001）。RYGB术后1周，NGT受试者的TBA曲线下面积（AUC）降低（术前，567 mmol·min/L[四分位间距，481 - 826]；1周，419[381 - 508]；P =.009），T2D患者未发生变化（894[573 - 1002]；695[349 - 1147]；P =.97），但两组均随术后时间升高（Ptime <.001）。RYGB术后空腹FGF19浓度急性未发生变化（NGT，140 pg/mL[100 - 162]，134[119 - 204]，P =.42；T2D，162[130 - 196]，154[104 - 164]，P =.68），且在整个随访期内保持不变。AUC FGF19随术后时间逐渐升高（Ptime <.001），类似于AUC TBA的变化。RYGB术后1周，葡萄糖代谢改善，低密度脂蛋白胆固醇和高密度脂蛋白胆固醇降低，胆囊收缩素和胰高血糖素样肽-1分泌增加，而游离脂肪酸浓度未发生变化。
TBA和FGF19不能解释RYGB后葡萄糖代谢、胆固醇组分和肠道激素分泌的急性变化。
