Poli Simone, Lange Naomi F, Brunasso Alessandro, Buser Angeline, Ballabani Edona, Melmer Andreas, Schiavon Michele, Tappy Luc, Herzig David, Dalla Man Chiara, Kreis Roland, Bally Lia
Magnetic Resonance Methodology, Institute of Diagnostic and Interventional Neuroradiology, University of Bern, Bern, Switzerland.
Translational Imaging Center, Sitem-Insel, Bern, Switzerland.
Diabetes Obes Metab. 2025 Jan;27(1):196-206. doi: 10.1111/dom.16001. Epub 2024 Oct 14.
Roux-en-Y gastric bypass (RYGB) surgery alters postprandial glucose profiles, causing post-bariatric hypoglycaemia (PBH) in some individuals. Due to the liver's central role in glucose homeostasis, hepatic glucose handling might differ in RYGB-operated patients with PBH compared to non-operated healthy controls (HC).
We enrolled RYGB-operated adults with PBH and HCs (n = 10 each). Participants ingested 60 g of [6,6'-H]-glucose (d-glucose) after an overnight fast. Deuterium metabolic imaging (DMI) with interleaved C magnetic resonance spectroscopy was performed before and until 150 min post-d-glucose intake, with frequent blood sampling to quantify glucose enrichment and gluco-regulatory hormones until 180 min. Glucose fluxes were assessed by mathematical modelling. Outcome trajectories were described using generalized additive models.
In RYGB subjects, the hepatic d-glucose signal increased early, followed by a decrease, whereas HCs exhibited a gradual increase and consecutive stabilization. Postprandial hepatic glycogen accumulation and the suppression of endogenous glucose production were lower in RYGB patients than in HCs, despite higher insulin exposure, indicating lower hepatic insulin sensitivity. The systemic rate of ingested d-glucose was faster in RYGB, leading to a higher, earlier plasma glucose peak and increased insulin secretion. Postprandial glucose disposal increased in RYGB patients, without between-group differences in peripheral insulin sensitivity.
Exploiting DMI with stable isotope flux analysis, we observed distinct postprandial hepatic glucose trajectories and parameters of glucose-insulin homeostasis in RYGB patients with PBH versus HCs. Despite altered postprandial glucose kinetics and higher insulin exposure, there was no evidence of impaired hepatic glucose uptake or output predisposing to PBH in RYGB patients.
Roux-en-Y胃旁路术（RYGB）可改变餐后血糖曲线，导致部分患者出现减重术后低血糖症（PBH）。由于肝脏在葡萄糖稳态中起核心作用，与未接受手术的健康对照者（HC）相比，接受RYGB手术且患有PBH的患者肝脏对葡萄糖的处理方式可能有所不同。
我们招募了接受RYGB手术且患有PBH的成年人以及健康对照者（每组n = 10）。参与者在禁食过夜后摄入60克[6,6'-H]-葡萄糖（d-葡萄糖）。在摄入d-葡萄糖前及摄入后150分钟内，采用交错C磁共振波谱进行氘代谢成像（DMI），并频繁采集血样以量化葡萄糖富集和糖调节激素，直至180分钟。通过数学建模评估葡萄糖通量。使用广义相加模型描述结果轨迹。
在接受RYGB手术的受试者中，肝脏d-葡萄糖信号早期升高，随后下降，而健康对照者则呈现逐渐升高并持续稳定的趋势。尽管胰岛素暴露量较高，但RYGB患者餐后肝脏糖原积累和内源性葡萄糖生成的抑制作用低于健康对照者，表明肝脏胰岛素敏感性较低。RYGB患者摄入d-葡萄糖的全身速率更快，导致血浆葡萄糖峰值更高、更早出现，胰岛素分泌增加。RYGB患者餐后葡萄糖处置增加，外周胰岛素敏感性在组间无差异。
通过利用稳定同位素通量分析的DMI，我们观察到接受RYGB手术且患有PBH的患者与健康对照者在餐后肝脏葡萄糖轨迹和葡萄糖-胰岛素稳态参数方面存在明显差异。尽管餐后葡萄糖动力学改变且胰岛素暴露量增加，但没有证据表明RYGB患者肝脏葡萄糖摄取或输出受损会导致PBH。
