PDF(Pubmed)
Abstract：
Environmental enteric dysfunction (EED) causes malnutrition in children in low-resource settings. Stable-isotope breath tests have been proposed as noninvasive tests of altered nutrient metabolism and absorption in EED, but uncertainty over interpreting the breath curves has limited their use. The activity of sucrose-isomaltase, the glucosidase enzyme responsible for sucrose hydrolysis, may be reduced in EED. We previously developed a mechanistic model describing the dynamics of the 13C-sucrose breath test (13C-SBT) as a function of underlying metabolic processes.
This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase.
We applied the mechanistic model to 2 sets of exploratory 13C-SBT experiments in healthy adult participants. First, 19 participants received differently labeled sucrose tracers (U-13C fructose, U-13C glucose, and U-13C sucrose) in a crossover study. Second, 16 participants received a sucrose tracer accompanied by 0, 100, and 750 mg of Reducose, a sucrase-isomaltase inhibitor. We evaluated a model-based diagnostic distinguishing between inhibitor concentrations using receiver operator curves, comparing with conventional statistics.
Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66-0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91-0.99).
Current summary approaches to interpreting 13C breath test curves may be limited to identifying only gross gut dysfunction. A mechanistic model-based approach improved interpretation of breath test curves characterizing sucrose metabolism.
This study aimed to determine which breath test curve dynamics are associated with sucrose hydrolysis and with the transport and metabolism of the fructose and glucose moieties and to propose and evaluate a model-based diagnostic for the loss of activity of sucrase-isomaltase.
We applied the mechanistic model to 2 sets of exploratory 13C-SBT experiments in healthy adult participants. First, 19 participants received differently labeled sucrose tracers (U-13C fructose, U-13C glucose, and U-13C sucrose) in a crossover study. Second, 16 participants received a sucrose tracer accompanied by 0, 100, and 750 mg of Reducose, a sucrase-isomaltase inhibitor. We evaluated a model-based diagnostic distinguishing between inhibitor concentrations using receiver operator curves, comparing with conventional statistics.
Sucrose hydrolysis and the transport and metabolism of the fructose and glucose moieties were reflected in the same mechanistic process. The model distinguishes these processes from the fraction of tracer exhaled and an exponential metabolic process. The model-based diagnostic performed as well as the conventional summary statistics in distinguishing between no and low inhibition [area under the curve (AUC): 0.77 vs. 0.66-0.79] and for low vs. high inhibition (AUC 0.92 vs. 0.91-0.99).
Current summary approaches to interpreting 13C breath test curves may be limited to identifying only gross gut dysfunction. A mechanistic model-based approach improved interpretation of breath test curves characterizing sucrose metabolism.
摘要：
背景：环境肠功能障碍（EED）会导致资源匮乏的儿童营养不良。已提出稳定同位素呼吸测试作为EED中改变的营养代谢和吸收的非侵入性测试，但是解释呼吸曲线的不确定性限制了它们的使用。蔗糖酶-异麦芽糖酶的活性，负责蔗糖水解的葡萄糖苷酶，可能会减少EED。我们先前开发了一个机械模型，该模型描述了13C-蔗糖呼吸测试（13C-SBT）的动力学，该动力学是潜在代谢过程的函数。
目的：1）确定哪些呼气试验曲线动力学与蔗糖水解以及果糖和葡萄糖部分的转运和代谢有关，和2）提出并评估基于模型的蔗糖酶-异麦芽糖酶活性丧失诊断方法。
方法：我们将机理模型应用于健康成人参与者的两组探索性13C-SBT实验。首先,19名参与者接受了不同标记的蔗糖示踪剂(U-13C果糖，U-13C葡萄糖,和U-13C蔗糖）在交叉研究中。第二,16名参与者接受了0毫克的蔗糖示踪剂，100毫克，和750毫克的Reducose®，蔗糖酶-异麦芽糖酶抑制剂。我们使用受试者操作曲线评估了基于模型的诊断区分抑制剂浓度，与传统统计数据相比。
结果：蔗糖水解以及果糖和葡萄糖部分的转运和代谢反映在相同的机理过程中。该模型将这些过程与呼气示踪剂的分数和指数代谢过程区分开来。在区分无抑制和低抑制（AUC0.77vs0.66-0.79）和低抑制与高抑制（AUC0.92vs0.91-0.99）方面，基于模型的诊断以及常规汇总统计。
结论：目前解释13C呼气试验曲线的总结方法可能仅限于识别总体肠功能障碍。基于机械模型的方法改进了表征蔗糖代谢的呼气测试曲线的解释。
目的：1）确定哪些呼气试验曲线动力学与蔗糖水解以及果糖和葡萄糖部分的转运和代谢有关，和2）提出并评估基于模型的蔗糖酶-异麦芽糖酶活性丧失诊断方法。
方法：我们将机理模型应用于健康成人参与者的两组探索性13C-SBT实验。首先,19名参与者接受了不同标记的蔗糖示踪剂(U-13C果糖，U-13C葡萄糖,和U-13C蔗糖）在交叉研究中。第二,16名参与者接受了0毫克的蔗糖示踪剂，100毫克，和750毫克的Reducose®，蔗糖酶-异麦芽糖酶抑制剂。我们使用受试者操作曲线评估了基于模型的诊断区分抑制剂浓度，与传统统计数据相比。
结果：蔗糖水解以及果糖和葡萄糖部分的转运和代谢反映在相同的机理过程中。该模型将这些过程与呼气示踪剂的分数和指数代谢过程区分开来。在区分无抑制和低抑制（AUC0.77vs0.66-0.79）和低抑制与高抑制（AUC0.92vs0.91-0.99）方面，基于模型的诊断以及常规汇总统计。
结论：目前解释13C呼气试验曲线的总结方法可能仅限于识别总体肠功能障碍。基于机械模型的方法改进了表征蔗糖代谢的呼气测试曲线的解释。
