Functional Examination of Pancreas Grafts by Mathematical Modelling of a Modified Intravenous Glucose Tolerance Test

Abstract

Background: Diabetes mellitus type I (DM1)is caused by an irreversible autoimmune destruction of insulin-secreting pancreatic beta-cells. Treatment of DM1 comprises substitution of insulin via exogenous application or transplantation of beta-cells. Pancreas transplantation (PTX) is currently the most definitive treatment of DM1. In PTX graft rejection is still the major problem with early diagnosis being a clinical challenge. Graft biopsy, the gold standard of rejection diagnosis, may put the patient at an extra procedural risk and there is a clear need for alternative preferentially non-invasive techniques. Mathematical models of the oral or intravenous glucose tolerance test (OGTT and IVGTT, respectively) have been proposed to serve this purpose. Study aim: The study is part of an interdisciplinary research effort to elucidate insulin-glucose dynamics in PTX patients. It aims to develop a practically feasible study protocol for a modified IVGTT (MIVGTT) which can be used further for mathematical modeling. Methods: After a baseline period (-10 to -2 min) a glucose-bolus (0.3g/kg BW; -2 to 0 min) is given, followed by high-dose glucose infusion (30g; 0 to 15 min), a glucagons-bolus (1mg; 15 min) and a low-dose glucose infusion (4g; 15 to 45 min). Serum levels of glucose, insulin and C-peptide are measured repeatedly over a period of 100 minutes (18 values). Results: Five studies (2 studies each in two PTX patients; 1 study in a healthy control) were done. The most important finding is a significantly stimulated insulin secretion following the glucagons bolus with high reproducibility in all subjects. Estimation of beta-cell mass was possible with the data obtained. Conclusion: The MIVGTT provides data suitable for mathematical modeling purposes aimed to estimate beta-cell mass.

Date of Award	2007
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Daniel Schneditz (Supervisor)