Alskär Oskar, Bagger Jonatan I, Røge Rikke M, Knop Filip K, Karlsson Mats O, Vilsbøll Tina, Kjellsson Maria C
Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
J Clin Pharmacol. 2016 Mar;56(3):340-8. doi: 10.1002/jcph.602. Epub 2015 Oct 12.
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.
整合葡萄糖 - 胰岛素(IGI)模型是一个先前发表的半机制模型,用于描述葡萄糖激发试验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,在不同葡萄糖剂量测试后,改进IGI模型对葡萄糖吸收和胃排空的描述。将所开发模型的性能与经验模型进行比较。为了开发我们的模型,使用了2型糖尿病患者和健康对照受试者口服和静脉注射葡萄糖激发试验的数据,以及小肠转运时间、葡萄糖对胃排空的抑制作用和葡萄糖在上皮细胞上的饱和吸收等现有知识,以改进IGI模型中胃排空和葡萄糖吸收的描述。发现十二指肠葡萄糖会抑制胃排空。无论应用何种胃排空模型,饱和葡萄糖吸收的性能均优于线性吸收。所开发的半生理模型比先前发表的经验模型表现更好,并且能够更好地理解葡萄糖吸收的潜在机制。总之,我们的新模型提供了更好的描述,并增进了对涉及口服葡萄糖的动态葡萄糖测试的理解。