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

http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = Med Biol Eng Comput (2015) 53:13611369 DOI 10.1007/s11517-015-1416-2

ORIGINAL ARTICLE

http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11517-015-1416-2&domain=pdf

Web End = Shortterm glucagon stimulation test of Cpeptide effecton glucose utilization in patients with type 1 diabetes mellitus

Viliam Mojto1 Zuzana Rausova2 Jana Chrenova2 Ladislav Dedik2

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 signicance of differences between parameters. A signicant difference between control and patient groups regarding the coefcient 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 coefcient 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 coefcient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

Received: 9 July 2014 / Accepted: 24 October 2015 / Published online: 25 November 2015 International Federation for Medical and Biological Engineering 2015

Keywords C-peptide Glucagon stimulation test Glucose utilization Pharmacodynamics Pharmacokinetics

1 Introduction

Glucagon is a peptide hormone that is produced by the -cells of the pancreatic islets and has a glycogenolytic effect, i.e., it increases the plasma glucose concentration, causing the release of insulin and C-peptide from the pancreatic -cells [11, 12, 23]. According to Ahrn et al. [1], in nondiabetic humans glucagon stimulates insulin secretion both directly and indirectly. Following glucagon injection, approximately 65 % of secreted insulin is extracted by the liver;...