Department of Information Engineering, University of Padova, Padova, Italy.
Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Front Endocrinol (Lausanne). 2021 Mar 15;12:611253. doi: 10.3389/fendo.2021.611253. eCollection 2021.
Assessment of insulin secretion is key to diagnose postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized complication following bariatric surgery. To this end, the Oral C-peptide Minimal Model (OCMM) can be used. This usually requires fixing C-peptide (CP) kinetics to the ones derived from the Van Cauter population model (VCPM), which has never been validated in PHH individuals. The objective of this work was to test the validity of the OCMM coupled with the VCPM in PHH subjects and propose a method to overcome the observed limitations. Two cohorts of adults with PHH after gastric bypass (GB) underwent either a 75 g oral glucose (9F/3M; age=42±9 y; BMI=28.3±6.9 kg/m) or a 60 g mixed-meal (7F/3M; age = 43 ± 11 y; BMI=27.5±4.2 kg/m) tolerance test. The OCMM was identified on CP concentration data with CP kinetics fixed to VCPM (VC approach). In both groups, the VC approach underestimated CP-peak and overestimated CP-tail suggesting CP kinetics predicted by VCPM to be inaccurate in this population. Thus, the OCMM was identified using CP kinetics estimated from the data (DB approach) using a Bayesian Maximum a Posteriori estimator. CP data were well predicted in all the subjects using the DB approach, highlighting a significantly faster CP kinetics in patients with PHH compared to the one predicted by VCPM. Finally, a simulation study was used to validate the proposed approach. The present findings question the applicability of the VCPM in patients with PHH after GB and call for CP bolus experiments to develop a reliable CP kinetic model in this population.
评估胰岛素分泌对于诊断餐后高胰岛素血症性低血糖（PHH）至关重要，这是一种越来越被认识到的减重手术后并发症。为此，可以使用口服 C 肽最小模型（OCMM）。这通常需要将 C 肽（CP）动力学固定到 Van Cauter 人群模型（VCPM）推导的动力学，而这在 PHH 个体中从未得到验证。本研究的目的是检验 OCMM 与 VCPM 结合在 PHH 个体中的有效性，并提出一种克服观察到的局限性的方法。两组胃旁路术后 PHH 成人分别接受 75g 口服葡萄糖（9F/3M；年龄=42±9 岁；BMI=28.3±6.9kg/m）或 60g 混合餐（7F/3M；年龄=43±11 岁；BMI=27.5±4.2kg/m）耐量试验。CP 动力学固定到 VCPM（VC 方法），CP 浓度数据上确定 OCMM。在两组中，VC 方法低估了 CP 峰，高估了 CP 尾，提示 VCPM 预测的 CP 动力学在该人群中不准确。因此，使用来自数据的 CP 动力学（DB 方法）通过贝叶斯最大后验估计器确定 OCMM。使用 DB 方法，所有受试者的 CP 数据均得到很好的预测，这突出表明 PHH 患者的 CP 动力学明显快于 VCPM 预测的动力学。最后，进行了一项模拟研究以验证所提出的方法。本研究结果对 VCPM 在胃旁路术后 PHH 患者中的适用性提出了质疑，并呼吁进行 CP 推注实验以在该人群中开发可靠的 CP 动力学模型。
