A Mathematical Model of the Oral Glucose Tolerance Test Illustrating the Effects of the Incretins

Abstract

Despite important empirical findings, current models of the oral glucose tolerance test (OGTT) do not incorporate the essential contributions of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, to glucose-stimulated insulin secretion. In order to address this deficiency, a model was, therefore, developed in which the incretins, as well as a term reflecting net hepatic glucose balance, were included. Equations modeling the changes in incretins, hepatic glucose balance, insulin and glucose were used to simulate the responses to 50 and 100 g oral glucose loads under normal conditions. The model successfully captures main trends in mean data from the literature using a simple 'lumped-parameter,' single-compartment approach in which the majority of the parameters were matched to known clinical data. The accuracy of the model and its applicability to understanding fundamental mechanisms was further assessed using a variety of glycemic and insulinemic challenges beyond those which the model was originally created to encompass, including hyper- and hypoinsulinemia, changes in insulin sensitivity, and the insulin infusion-modified intravenous glucose tolerance test.

Sistema Bayesiano para la Predicción de la Diabetes

“…Aunque los clasificadores Bayesianos han sido usados en problemas relacionados (Magni et al, 2010), así como en algunos modelos matemáticos (Klinke, 2007;Morbiducci et al, 2014;Brubaker et al, 2007), no se encontraron trabajos centrados en la identificación temprana de enfermedades como la diabetes. Por otro lado, aunque el clasificador Bayesiano propuesto logra resultados similares a los obtenidos por otros autores, cuando la variable insulina en suero fue incorporada, la capacidad de predicción mostró resultados muy superiores a los reportados en la literatura.…”

Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test

“…We write the equation describing the kinetics of total GIP in plasma in the following form; see also (5) …”

“…A retention of 5% of the glucose load was estimated to occur at ϳ130 min and at ϳ193 min for a load of 50 and 100 g, respectively. Different mathematical models describing the gastric emptying and the intestinal absorption have been proposed over time (5,11,26,36). Although limited data have been found on the small intestinal transit time of glucose, this time appears to be in the range of 3-4 h (1, 39).…”

Personalized metabolic profile estimations using oral glucose tolerance tests

“…However, the structure of this model is not appropriate for use with OGTTs, because its structure is too simple, and some important information, such as the insulin and glucose dynamics in major organs, could be lost (Caumo et al, 1996). Many attempts have been made to generate an OGTT model (Brubaker et al, 2007;Dalla Man et al, 2007;Hovorka et al, 2004;Lehmann and Deutsch, 1992;Thomaseth et al, 1996). Some recent sophisticated models that included incretin dynamics to incorporate intestinal glucose absorption were developed (Brubaker et al, 2007;Burattini and Morettini, 2012;Dalla Man et al, 2007;Kim et al, 2014).…”

“…Many attempts have been made to generate an OGTT model (Brubaker et al, 2007;Dalla Man et al, 2007;Hovorka et al, 2004;Lehmann and Deutsch, 1992;Thomaseth et al, 1996). Some recent sophisticated models that included incretin dynamics to incorporate intestinal glucose absorption were developed (Brubaker et al, 2007;Burattini and Morettini, 2012;Dalla Man et al, 2007;Kim et al, 2014). However, no models have attempted to describe the dynamic interaction between glucose and insulin and to isolate individualised physiological data from OGTT data.…”