An Extended Minimal Model of OGTT: Estimation of Alpha- and Beta-Cell Dysfunction, Insulin Resistance, and the Incretin Effect

Am J Physiol Endocrinol Metab. 2023 Dec 13. doi: 10.1152/ajpendo.00278.2023. Online ahead of print.ABSTRACTLoss of insulin sensitivity, alpha- and beta-cell dysfunction, and impairment in incretin effect have all been implicated in the pathophysiology of type 2 diabetes (T2D). Parsimonious mathematical models are useful in quantifying parameters related to the pathophysiology of T2D. Here we extend the minimum model developed to describe the glucose-insulin-glucagon dynamics in the intravenous glucose infusion (IIGI) experiment to the oral glucose tolerance test (OGTT). The extended model describes glucose and hormone dynamics in OGTT including the contribution of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), to insulin secretion. A new function describing glucose arrival from the gut is introduced. The model is fitted to OGTT data from 8 patients with T2D and 8 weight-matched control subjects (CS) without diabetes to obtain parameters related to insulin sensitivity, beta- and alpha-cell function. The parameters, i.e., measures of insulin sensitivity, a1, suppression of glucagon secretion, k1, magnitude of glucagon secretion, g2, and incretin-dependent insulin secretion, g3, were found to be significantly different between CS and T2D with p values < .002, < .017, < .009, < .004, respectively. A new rubric for estimating the incretin effect directly from modeling the OGTT is presented. The average incretin ef...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Source Type: research