Short-term glucagon stimulation test of C-peptide effect on glucose utilization in patients with type 1 diabetes mellitus

Abstract

This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30 min after 1 mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p ≪ 0.001 and p = 0.002, respectively) was observed. The high correlation (r = 0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

Mathematical Model of Glucagon Kinetics for the Assessment of Insulin-Mediated Glucagon Inhibition During an Oral Glucose Tolerance Test

“…As previously outlined, some mathematical models were developed with the aim to investigate glucagon secretion at cellular level (12)(13)(14)(15)(16)(17)(18)(19)(20)(21), whereas other models, more similarly to ours, were developed for whole-body analyses, but mainly for simulation purposes rather than for clinical applications (22)(23)(24)(25). Other studies presented models of glucagon kinetics for possible clinical applications, but they were focused on the analysis of glucagon administered exogenously, or for the analysis of the not common glucagon challenge test (26)(27)(28)(29). The study having more aspects in common with ours is that of Kelly et al (30).…”

“…One study analyzed the kinetics of glucagon administered exogenously ( 26 ), without however accounting for the interplay with insulin or glucose; another study performed similar analyses for the case of therapy based on glucagon (plus insulin) infusion ( 27 ). Some other studies developed models for the analysis of the glucagon challenge test, which is however not widely used ( 28 , 29 ). The study ( 30 ) had purposes more similar to those of our study, but the developed model analyzed glucagon kinetics during an intravenous glucose tolerance test (IVGTT), or an insulin-infusion test.…”

Special issue on emerging technologies for the management of diabetes mellitus

“…Toward this direction, compartmental modeling approaches have been applied in order to evaluate the effect of insulin, glucagon and C-peptide on glucose utilization [10]. Villiam Mojito et al [5] propose a methodological framework based on pharmacokinetic/ pharmacodynamic (PK/PD) modeling strategy, in order to model the effect of C-peptide on glucose utilization after injection of a glucagon bolus in patients with T1DM.…”

Effects of mixed meal tolerance test on gastric emptying, glucose and lipid homeostasis in obese nonhuman primates

“…In condition with impaired insulin secretion such as in insulin-dependent type 1 and type 2 diabetes mellitus (T2DM), the MMTT is used to assess β-cell function and is regarded as more physiological than the glucagon stimulation test (GST), which is a standard measure of endogenous insulin secretion 2 – 4 . Glucagon is a potent stimulus for the islet beta-cell and intravenous bolus injection of 1 mg glucagon has been widely used to assess endogenous insulin secretion for clinical and research purposes 3 – 5 . MMTT-induced stimulation of insulin release involves an enteroinsular axis via incretin hormones, such as gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), amongst others.…”