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An Integrated Model for Glucose and Insulin Regulation in Healthy Volunteers and Type 2 Diabetic Patients Following Intravenous Glucose Provocations

From the Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, University of Uppsala, Sweden (Ms Silber, Ms Jauslin, Dr Simonsson, Dr Karlsson); and Clinical Pharmacology, Modeling and Simulation Group, F. Hoffmann-La Roche Inc, Basel, Switzerland (Ms Jauslin, Dr Frey, Dr Gieschke).

An integrated model for the regulation of glucose and insulin concentrations following intravenous glucose provocations in healthy volunteers and type 2 diabetic patients was developed. Data from 72 individuals were included. Total glucose, labeled glucose, and insulin concentrations were determined. Simultaneous analysis of all data by nonlinear mixed effect modeling was performed in NONMEM. Integrated models for glucose, labeled glucose, and insulin were developed. Control mechanisms for regulation of glucose production, insulin secretion, and glucose uptake were incorporated. Physiologically relevant differences between healthy volunteers and patients were identified in the regulation of glucose production, elimination rate of glucose, and secretion of insulin. The model was able to describe the insulin and glucose profiles well and also showed a good ability to simulate data. The features of the present model are likely to be of interest for analysis of data collected in antidiabetic drug development and for optimization of study design.

Key Words: Glucose homeostasis • hot glucose • IVGTT • NONMEM

Address for correspondence: Hanna E. Silber, Box 591, SE-751 24 Uppsala, Sweden.

This article has been cited by other articles:

				P. M. Jauslin, H. E. Silber, N. Frey, R. Gieschke, U. S. H. Simonsson, K. Jorga, and M. O. Karlsson An Integrated Glucose-Insulin Model to Describe Oral Glucose Tolerance Test Data in Type 2 Diabetics J. Clin. Pharmacol., October 1, 2007; 47(10): 1244 - 1255. [Abstract] [Full Text] [PDF]