computer methods and programs in biomedicine 95 ( 2 0 0 9 ) 1–9 journal homepage: www.intl.elsevierhealth.com/journals/cmpb Computer controlled sequential simulation method: Reconsidering evaluation of measurements from frequently sampled intravenous glucose tolerance test Ladislav Dedík a,* , Martina Tvrdo ˇ nová a , Mária ˇ Duri ˇ sová b , Adela Penesová c , Daniela Mikloviˇ cová d , Marián Kozlovsk ´ y e a Institute of Automation, Measurement and Applied Informatics, Faculty of Mechanical Engineering, Slovak University of Technology, Bratislava, Slovak Republic b Institute of Experimental Pharmacology, Slovak Academy of Science, Bratislava, Slovak Republic c Institute of Experimental Endocrinology, Slovak Academy of Science, Bratislava, Slovak Republic d Medical School of Comenius University, Bratislava, Slovak Republic e National Institute of Cardiovascular diseases, Bratislava, Slovak Republic article info Article history: Received 19 June 2008 Received in revised form 25 November 2008 Accepted 1 January 2009 Keywords: Cessation of glucose output Glucose clearance Glucose uptake FSIVGTT Linear dynamic model abstract This work describes quantification of regulatory mechanisms glucose–insulin, using data from a frequently sampled intravenous glucose tolerance test (FSIVGTT) and a mechanis- tically motivated model with time delays. FSIVGTT was performed on 14 young healthy volunteers. The constructed model computationally takes into account the form of the short-time glucose infusion used. Estimated model parameters are used to derive relation- ships quantifying the following mechanisms of regulatory systems glucose–insulin of the volunteers enrolled: (1) glucose uptake by body cells; (2) cessation (suppression) of glucose output from liver; (3) glucose clearance. The model presented correctly approximates ini- tial peaks and subsequent waves in plasma glucose concentration–time profiles after the glucose infusion. These results indicate that the model presented is an appropriate tool for assessing glucose behavior during a FSIVGTT. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The intravenous glucose tolerance test, as regular or fre- quently sampled (FSIVGTT), is a tool for investigation of dynamic behavior of glucose in the body [1]. Several meth- ods have been proposed to evaluate measurements from FSIVGTT, and to produce complex portrait of the multi- faceted glucose–insulin interaction, or in other words of the glucose–insulin control system (G-I CS), see, e.g. studies [2–7]. Insulin sensitivity indexes [7] are conventionally calculated in evaluations of measurements from FSIVGTT. In contrast, ∗ Corresponding author. Tel.: +421 2 5729 4559; fax: +421 2 5729 4559. E-mail address: ladislav.dedik@stuba.sk (L. Dedík). the present study is aimed at quantification of the following regulatory glucose–insulin regulatory mechanisms: (1) glucose uptake by body cells; (2) cessation (suppression) of glucose output from liver; (3) glucose clearance [8]. After oral and intravenous glucose administration, plasma glucose concentration increases over its basal level, and insulin production in pancreas  cells increases simultane- ously, see Fig. 1. The latter process not only initiates glucose uptake by body cells (denoted effect E 1 in this work), but it also induces a temporal cessation of endogenous glucose pro- duction (denoted effect E 2 in this work). As a result, plasma 0169-2607/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.cmpb.2009.01.001