Integral-based identification of a physiological insulin and glucose model on euglycaemic clamp trials and IVGTT trials (Invited)

Modelling can enhance the diagnosis and control of metabolic disorders. Clinical effectiveness demands physiological accuracy, patient specificity and identification with limited data. A two-compartment insulin kinetics model and associated insulin-glucose pharmacodynamics are presented. Similarities with a well validated C-peptide model are used to simplify parameter identification. Critical patient specific parameters are identified using a novel convex, integral-based method. The model and methods are validated using euglycaemichyperinsulinemic clamp data (N=146). The identified parameter values are within reported physiological ranges. The mean errors in the resulting glucose and insulin profiles are eG = 5.9% ± 6.6% SD and eI = 6.2% ± 6.4% SD, which are within measurement error.

[1]  K. Polonsky,et al.  Alterations in the glucose-stimulated insulin secretory dose-response curve and in insulin clearance in nondiabetic insulin-resistant individuals. , 1997, The Journal of clinical endocrinology and metabolism.

[2]  S. Silbernagl,et al.  Color atlas of physiology , 1981 .

[3]  K. Tranberg,et al.  Modeling of plasma disappearance of unlabeled insulin in man. , 1978, The American journal of physiology.

[4]  C. Doran,et al.  Modelling and control of hyperglycemia in critical care patients , 2004 .

[5]  A Mari,et al.  Dose-response characteristics of insulin action on glucose metabolism: a non-steady-state approach. , 2000, American journal of physiology. Endocrinology and metabolism.

[6]  L. Strindberg,et al.  Delayed transcapillary delivery of insulin to muscle interstitial fluid after oral glucose load in obese subjects. , 2005, Diabetes.

[7]  C Cobelli,et al.  The kinetics of insulin in man. II. Role of the liver. , 1987, Diabetes/metabolism reviews.

[8]  C Cobelli,et al.  Estimation of β-Cell Sensitivity From Intravenous Glucose Tolerance Test C-Peptide Data: Knowledge of the Kinetics Avoids Errors in Modeling the Secretion , 1995, Diabetes.

[9]  H. Gerstein,et al.  Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview , 2000, The Lancet.

[10]  Jeppe Sturis,et al.  Estimation of Insulin Secretion Rates from C-Peptide Levels: Comparison of Individual and Standard Kinetic Parameters for C-Peptide Clearance , 1992, Diabetes.

[11]  R. Hovorka,et al.  Measuring prehepatic insulin secretion using a population model of C-peptide kinetics: accuracy and required sampling schedule , 1998, Diabetologia.

[12]  J Geoffrey Chase,et al.  Targeted glycemic reduction in critical care using closed-loop control. , 2005, Diabetes technology & therapeutics.

[13]  J. Mann,et al.  Intensive lifestyle changes are necessary to improve insulin sensitivity: a randomized controlled trial. , 2002, Diabetes care.

[14]  I. Deary,et al.  Insulin resistance , 1996 .

[15]  S E Kahn,et al.  The effect of insulin dose on the measurement of insulin sensitivity by the minimal model technique. Evidence for saturable insulin transport in humans. , 1996, The Journal of clinical investigation.

[16]  Piero Marchetti,et al.  Phasic insulin release and metabolic regulation in type 2 diabetes. , 2002, Diabetes.

[17]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[18]  Christopher E. Hann,et al.  Impact of insulin-stimulated glucose removal saturation on dynamic modelling and control of hyperglycaemia , 2005, Int. J. Intell. Syst. Technol. Appl..

[19]  T. Brundin.  Splanchnic and extrasplanchnic extraction of insulin following oral and intravenous glucose loads. , 1999, Clinical science.

[20]  W. Boron,et al.  Medical physiology : a cellular and molecular approach , 2002 .

[21]  R. Eaton,et al.  Insulin removal in man: in vivo evidence for a receptor-mediated process. , 1984, The Journal of clinical endocrinology and metabolism.

[22]  Christopher E. Hann,et al.  Integral-based parameter identification for long-term dynamic verification of a glucose-insulin system model , 2005, Comput. Methods Programs Biomed..

[23]  Barry A. Mizoch.  Alterations in Fuel Metabolism in Critical Illness , 1997 .

[24]  Y. Z. Ider,et al.  Quantitative estimation of insulin sensitivity. , 1979, The American journal of physiology.

[25]  M Berman,et al.  A model of the kinetics of insulin in man. , 1974, The Journal of clinical investigation.

[26]  R. Walker,et al.  Diagnosing insulin resistance in the general population. , 2001, Diabetes care.

[27]  K. M. Erickson,et al.  Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. , 1980, The Journal of clinical endocrinology and metabolism.

[28]  M Berman,et al.  Modeling the insulin-glucose system in man. , 1974, Federation proceedings.