MATHEMATICAL MODEL OF GLUCOSE-INSULIN SYSTEM USING THE MODIFIED ORAL MINIMAL MODEL AND THE INCRETIN EFFECTS

Abstract

Objective: Current models of the oral glucose tolerance test (OGTT) do not contain the substantive contributions of the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), to glucose-stimulated insulin secretion. In this paper, the modified oral minimal model and the incretin effects were introduced. Mathematical model of glucose levels and the changes in incretin was used to simulate the responses to 75 grams oral glucose loads under normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM).

Methods: In the standard OGTT, plasma glucose concentrations are measured at time 0, 10, 20, 30, 60, 90, 120, 150, and 180 min, following an oral glucose load of 75 grams. The OGTT is a simple clinical test currently used to aid diagnosis of NGT, IGT, and T2DM subjects. In this work, the modified oral minimal model and the incretin effects were used to study investigated in the published data of the OGTT.

Results: The accuracy of the model and its applicability to understanding fundamental mechanisms was further assessed using the calculated coefficient of determination, R², from parameter estimates and the majority of the parameters were matched to known experimental data. The averaged R²value between measured and calculated plasma concentrations is 0.920, which indicates agreement with experiment data.

Conclusion: The loss of incretin effects is secondary to the development of diabetes. Thus, patients with diabetes secondary to destruction of insular tissues in patients with chronic pancreatitis exhibit an almost complete loss of incretin effects, whereas patients with a similar degree of chronic pancreatitis, as judged from pancreatic function tests but normal glucose tolerance (NGT), have a normal uncertain effect.