描述健康受试者和2型糖尿病患者胃排空和葡萄糖吸收的半机制模型。

IF 2.9 4区 医学 Journal of Clinical Pharmacology Pub Date : 2016-03-01 Epub Date: 2015-10-12 DOI:10.1002/jcph.602
Oskar Alskär, Jonatan I Bagger, Rikke M Røge, Filip K Knop, Mats O Karlsson, Tina Vilsbøll, Maria C Kjellsson
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引用次数: 17

摘要

葡萄糖-胰岛素综合模型(IGI)是一种先前发表的半机制模型,描述了葡萄糖刺激后的血浆葡萄糖和胰岛素浓度。这项工作的目的是利用生理学知识来改进IGI模型在不同葡萄糖剂量试验后对葡萄糖吸收和胃排空的描述。将所建立模型的性能与经验模型进行了比较。为了建立我们的模型,我们将2型糖尿病患者和健康对照者口服和静脉注射葡萄糖的数据与小肠转运时间、葡萄糖抑制胃排空和上皮上葡萄糖的饱和吸收的现有知识结合起来,以改善IGI模型中胃排空和葡萄糖吸收的描述。十二指肠葡萄糖可抑制胃排空。无论采用何种胃排空模型,饱和葡萄糖的吸收性能都优于线性吸收。开发的半生理模型比以前发表的经验模型表现得更好,并且可以更好地理解葡萄糖吸收的机制。总之,我们的新模型提供了一个更好的描述,提高了对动态葡萄糖测试的理解,包括口服葡萄糖。
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Semimechanistic model describing gastric emptying and glucose absorption in healthy subjects and patients with type 2 diabetes.

The integrated glucose-insulin (IGI) model is a previously published semimechanistic model that describes plasma glucose and insulin concentrations after glucose challenges. The aim of this work was to use knowledge of physiology to improve the IGI model's description of glucose absorption and gastric emptying after tests with varying glucose doses. The developed model's performance was compared to empirical models. To develop our model, data from oral and intravenous glucose challenges in patients with type 2 diabetes and healthy control subjects were used together with present knowledge of small intestinal transit time, glucose inhibition of gastric emptying, and saturable absorption of glucose over the epithelium to improve the description of gastric emptying and glucose absorption in the IGI model. Duodenal glucose was found to inhibit gastric emptying. The performance of the saturable glucose absorption was superior to linear absorption regardless of the gastric emptying model applied. The semiphysiological model developed performed better than previously published empirical models and allows better understanding of the mechanisms underlying glucose absorption. In conclusion, our new model provides a better description and improves the understanding of dynamic glucose tests involving oral glucose.

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来源期刊
Journal of Clinical Pharmacology
Journal of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
自引率
3.40%
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期刊介绍: The Journal of Clinical Pharmacology (JCP) is a Human Pharmacology journal designed to provide physicians, pharmacists, research scientists, regulatory scientists, drug developers and academic colleagues a forum to present research in all aspects of Clinical Pharmacology. This includes original research in pharmacokinetics, pharmacogenetics/pharmacogenomics, pharmacometrics, physiologic based pharmacokinetic modeling, drug interactions, therapeutic drug monitoring, regulatory sciences (including unique methods of data analysis), special population studies, drug development, pharmacovigilance, womens’ health, pediatric pharmacology, and pharmacodynamics. Additionally, JCP publishes review articles, commentaries and educational manuscripts. The Journal also serves as an instrument to disseminate Public Policy statements from the American College of Clinical Pharmacology.
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