An Integrated Glucose‐Insulin Model to Describe Oral Glucose Tolerance Test Data in Type 2 Diabetics

Abstract

An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

“…The estimated PD parameters are summarized in Table III. In general, the final estimated parameters controlling glucose turnover are in good agreement with literature values (20)(21)(22)(28)(29)(30)(31)(32). The population mean estimate of baseline glucose concentration was 161 mg/dL and displayed 37.1% variability between occasions.…”

“…However, the current model could be further improved and extended with such measurements. The negative feedback triggered by increases of glucose concentration on the endogenous production k in was evaluated similarly as in the literature (20,21). The estimated parameters related to either a direct glucose effect on its own production or an indirect feedback with delay were negligible, which is consistent with an expectation of lack of significant glucose feedback on its own production in diabetic patients (20,21).…”

“…We examined different gastric emptying models. Oral ingestion of glucose from meals represents a key component in the model; two published models were examined (21,22). The first model used a semiphysiological model mimicking glucose transit through the gastrointestinal (GI) tract before reaching the systemic circulation and assumed two compartments for stomach and one compartment for intestine (22).…”

“…The first model used a semiphysiological model mimicking glucose transit through the gastrointestinal (GI) tract before reaching the systemic circulation and assumed two compartments for stomach and one compartment for intestine (22). In the second model, a series of transit steps described glucose absorption after an oral glucose tolerance test (21). Both models have a first-order rate constant for glucose transit through the GI tract.…”

Decreased Beta Cell Function and Insulin Sensitivity Contributed to Coronary Artery Disease in Patients with Normal Glucose Tolerance

“…In group 3, 44 patients had two diseased vessels and 30 patients had three diseased vessels. hyperglycemic clamp techniques [13][14][15] . Models of the glucose-insulin system are widely used in clinical studies.…”