Dept. of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Int J Obes (Lond). 2023 Nov;47(11):1143-1151. doi: 10.1038/s41366-023-01372-8. Epub 2023 Aug 31.
BACKGROUND/OBJECTIVES: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.
SUBJECTS/METHODS: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.
On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).
Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.
背景/目的：在 Roux-en-Y 胃旁路手术后（RYGB），一部分患者从未获得超过 50%的超重指数（BMI）减轻（EBMIL），并被归类为原发性体重减轻（WL）失败。我们假设，与成功维持 WL 的患者相比，原发性 WL 失败患者的餐后胰高血糖素样肽 1（GLP-1）和肽 YY（PYY）浓度会更低。此外，抑制肠道激素分泌会导致原发性 WL 失败患者的自由进食量减少。
研究对象/方法：20 名原发性 WL 失败（低 EBMIL < 50%）的女性患者与 20 名成功维持 WL（高 EBMIL > 60%）的女性患者按年龄、术前 BMI 和 RYGB 术后时间进行个体化匹配。在随机顺序的不同日子里，对患者进行皮下注射奥曲肽或生理盐水（安慰剂），然后给予固定早餐和自由午餐，并采集食欲调节激素和视觉模拟量表（VAS）评分来评估饥饿/饱腹感。此外，参与者还进行了 GLP-1、PYY 及其受体的基因变异分析、间接热量测定、双能 X 射线吸收法（DXA）扫描、4 天家庭食物登记和 14 天计步。
在安慰剂日，早餐后两组间餐后 GLP-1、PYY 和胆囊收缩素（CCK）浓度相似。低 EBMIL 患者空腹胃饥饿素水平较低，但餐后抑制程度相似。低 EBMIL 患者的饱腹感 VAS 评分较低，饥饿感 VAS 评分抑制程度较低。两组间基因变异无差异。奥曲肽降低了两组的 GLP-1、PYY、CCK 和胃饥饿素浓度。奥曲肽对低 EBMIL 的自由进食量没有影响（-1%[-13，12]，平均值[95%CI]），而在高 EBMIL 中，进食量增加了 23%[2，44]。
RYGB 后原发性 WL 失败的特征不是调节食欲的肠道激素分泌受损。有趣的是，奥曲肽抑制肠道激素分泌仅增加了 RYGB 后成功维持 WL 的患者的食物摄入量。因此，肠道激素对中枢摄食反应受损可能导致 RYGB 后原发性 WL 失败。
