Simple Parameters Describing Gut Absorption and Lipid Dynamics in Relation to Glucose Metabolism During a Routine Oral Glucose Test

The oral glucose tolerance test (OGTT) is a simple and physiological test used for the diagnosis of diabetes and, more generally, for the assessment of the metabolic condition of an individual. For a deep analysis of the OGTT data, the exploitation of mathematical models for the interpretation of the test results is necessary. The focus of this chapter is on some recent models based on OGTT data, describing the glucose absorption from the gut, and the effects of insulin on the dynamics of non-esterified free fatty acids (NEFA). As regards the glucose absorption model, it requires measure of plasma glucose and insulin during the OGTT. The model allows the estimation of absorption rates, the total glucose absorbed, and half-life in the gastrointestinal tract. In fact, the increase of postprandial circulating plasma glucose over time is the result of gain from gut glucose absorption and liver endogenous glucose production, and loss because of glucose uptake, predominantly by skeletal muscle. Endogenous glucose production can be assessed by some mathematical expressions depending on plasma insulin values, whereas the glucose loss is calculated as a function of the endogenous glucose production and of the insulin sensitivity in each individual. Once these variables have been determined, glucose absorption can be determined by solving a nonlinear least squares problem fitting the plasma glucose values during the OGTT. The model was used to analyze sex related differences in OGTT glucose metabolism, including gut absorption, in healthy humans. We found that, in the early phase of the OGTT, males had markedly increased glucose absorption rates by approximately 200 mg/min from the gastrointestinal tract, whereas in the final phase of the OGTT, females absorbed approximately 60 mg/min more glucose. In another study, the model was used to assess glucose absorption in 15 pregnant women with gestational diabetes. As regards the model of NEFA dynamics, it was postulated that NEFA kinetics could be described by first order (single compartment) kinetics, with NEFA production controlled by insulin in remote compartment. It is assumed that plasma insulin enters a remote compartment, before having an inhibitory effect on NEFA production. Starting from basal production at basal insulin, NEFA production decreases, for suprabasal increase in remote insulin up to a prescribed value. The identification of the unknown parameters of the model was performed by applying Genetic Algorithms. The model was used to study NEFA kinetics in a group of women with a history of gestational diabetes (fGDM). The fGDM women were divided into normal glucose tolerance group (NGT) and a impaired glucose metabolism (IGM). We also studied 15 control (CNT) women. We found that, while fasting NEFA were not different between groups, IGM exhibited slower decline in plasma NEFA during the OGTT. We conclude that appropriate mathematical modeling allows sophisticated analyses of the OGTT data, thus possibly providing a comprehensive picture of the metabolic condition.