Pavan J, Dalla Man C, Herzig D, Bally L, Del Favero S
Annu Int Conf IEEE Eng Med Biol Soc. 2021 Nov;2021:677-680. doi: 10.1109/EMBC46164.2021.9630223.
Post-prandial hypoglycemia occurs 2-5 hours after food intake, in not only insulin-treated patients with diabetes but also other metabolic disorders. For example, postprandial hypoglycemia is an increasingly recognized late metabolic complication of bariatric surgery (also known as PBH), particularly gastric bypass. Underlying mechanisms remain incompletely understood to date. Besides excessive insulin exposure, impaired counter-regulation may be a further pathophysiological feature. To test this hypothesis, we need standardized postprandial hypoglycemic clamp procedures in affected and unaffected individuals allowing to reach identical predefined postprandial hypoglycemic trajectories. Generally, in these experiments, clinical investigators manually adjust glucose infusion rate (GIR) to clamp blood glucose (BG) to a target hypoglycemic value. Nevertheless, reaching the desired target by manual adjustment may be challenging and possible glycemic undershoots when approaching hypoglycemia can be a safety concern for patients. In this study, we developed a PID algorithm to assist clinical investigators in adjusting GIR to reach the predefined trajectory and hypoglycemic target. The algorithm is developed in a manual mode to permit the clinical investigator to interfere. We test the controller in silico by simulating glucose-insulin dynamics in PBH and healthy nonsurgical individuals. Different scenarios are designed to test the robustness of the algorithm to different sources of variability and to errors, e.g. outliers in the BG measurements, sampling delays or missed measurements. The results prove that the PID algorithm is capable of accurately and safely reaching the target BG level, on both healthy and PBH subjects, with a median deviation from reference of 2.8% and 2.4% respectively.Clinical relevance- This control algorithm enables standardized, accurate and safe postprandial hypoglycemic clamps, as evidenced in silico in PBH patients and controls.
餐后低血糖发生在进食后2 - 5小时，不仅见于接受胰岛素治疗的糖尿病患者，也见于其他代谢紊乱患者。例如，餐后低血糖是减肥手术（也称为PBH，尤其是胃旁路手术）一种越来越被认识到的晚期代谢并发症。其潜在机制至今仍未完全明了。除了胰岛素暴露过多外，反调节受损可能是另一个病理生理特征。为了验证这一假设，我们需要在受影响和未受影响的个体中采用标准化的餐后低血糖钳夹程序，以达到相同的预定义餐后低血糖轨迹。一般来说，在这些实验中，临床研究人员手动调整葡萄糖输注速率（GIR）以将血糖（BG）钳夹到目标低血糖值。然而，通过手动调整达到期望目标可能具有挑战性，并且接近低血糖时可能出现的血糖过低情况对患者来说可能是一个安全问题。在本研究中，我们开发了一种PID算法来协助临床研究人员调整GIR以达到预定义轨迹和低血糖目标。该算法以手动模式开发，以便临床研究人员进行干预。我们通过模拟PBH患者和健康非手术个体的葡萄糖 - 胰岛素动态在计算机上对控制器进行测试。设计了不同的场景来测试该算法对不同变异性来源和误差的鲁棒性，例如BG测量中的异常值、采样延迟或测量缺失。结果证明，PID算法能够在健康受试者和PBH受试者中准确且安全地达到目标BG水平，与参考值的中位数偏差分别为2.8%和2.4%。临床相关性——这种控制算法能够实现标准化、准确且安全的餐后低血糖钳夹，这在PBH患者和对照的计算机模拟中得到了证明。
