A mathematical model of the euglycemic hyperinsulinemic clamp

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A mathematical model of the euglycemic hyperinsulinemic clamp Umberto Picchini*1, Andrea De Gaetano1, Simona Panunzi1, Susanne Ditlevsen2 and Geltrude Mingrone3 Address: 1CNR-IASI BioMatLab, Rome, Italy, 2Department of Biostatistics, University of Copenhagen, Denmark and 3Istituto di Medicina Interna e Geriatria, Divisione di Malattie del Ricambio, Università Cattolica del Sacro Cuore, Policlinico Universitario "A. Gemelli", Rome, Italy Email: Umberto Picchini* - [email protected]; Andrea De Gaetano - [email protected]; Simona Panunzi - [email protected]; Susanne Ditlevsen - [email protected]; Geltrude Mingrone - [email protected] * Corresponding author

Published: 03 November 2005 Theoretical Biology and Medical Modelling 2005, 2:44

doi:10.1186/1742-4682-2-44

Received: 05 August 2005 Accepted: 03 November 2005

This article is available from: http://www.tbiomed.com/content/2/1/44 © 2005 Picchini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Background: The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity, and in its usual form the patient is followed under insulinization for two hours. In the present study, sixteen subjects with BMI between 18.5 and 63.6 kg/m2 were studied by long-duration (five hours) EHC. Results: From the results of this series and from similar reports in the literature it is clear that, in obese subjects, glucose uptake rates continue to increase if the clamp procedure is prolonged beyond the customary 2 hours. A mathematical model of the EHC, incorporating delays, was fitted to the recorded data, and the insulin resistance behaviour of obese subjects was assessed analytically. Obese subjects had significantly less effective suppression of hepatic glucose output and higher pancreatic insulin secretion than lean subjects. Tissue insulin resistance appeared to be higher in the obese group, but this difference did not reach statistical significance. Conclusion: The use of a mathematical model allows a greater amount of information to be recovered from clamp data, making it easier to understand the components of insulin resistance in obese vs. normal subjects.

Background With the growing epidemiological importance of insulin resistance states such as obesity and Type 2 Diabetes Mellitus, T2DM, and with increasing clinical recognition of the impact of the so-called metabolic syndrome, the assessment of insulin sensitivity has become highly relevant to metabolic research. The experimental procedures currently employed to gather information on the degree of insulin resistance of a subject are the Oral Glucose Tolerance Test (OGTT), the

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