Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

Glucose-insulin system models are commonly used for identifying insulin sensitivity. With physiological, 2-compartment insulin kinetics models, accurate kinetic parameter values are required for reliable estimates of insulin sensitivity. This study uses data from 6 published microdialysis studies to determine the most appropriate parameter values for the transcapillary diffusion rate (n(I)) and cellular insulin clearance rate (n(C)). The 6 studies (12 data sets) used microdialysis techniques to simultaneously obtain interstitial and plasma insulin concentrations. The reported plasma insulin concentrations were used as input and interstitial insulin concentrations were simulated with the interstitial insulin kinetics sub-model. These simulated results were then compared to the reported interstitial measurements and the most appropriate set of parameter values was determined across the 12 data sets by combining the results. Interstitial insulin kinetic parameters values n(I)=n(C)=0.0060 min⁻¹ were shown to be the most appropriate. These parameter values are associated with an effective, interstitial insulin half-life, t(½)=58 min, within the range of 25-130 min reported by others.

[1]  Alan D. Cherrington,et al.  The Endocrine pancreas and regulation of metabolism , 2001 .

[2]  A. Caumo,et al.  First-phase insulin secretion: does it exist in real life? Considerations on shape and function. , 2004, American journal of physiology. Endocrinology and metabolism.

[3]  W. Waldhäusl,et al.  Essentials of insulin pharmacokinetics. , 1988, Wiener klinische Wochenschrift.

[4]  S. Lillioja,et al.  Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men. , 1994, The Journal of clinical investigation.

[5]  L. Lönn,et al.  Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects. , 2002, Diabetes.

[6]  Geoffrey M. Shaw,et al.  Derivative weighted active insulin control algorithms and intensive care unit trials , 2005 .

[7]  M. Roden,et al.  Transcapillary insulin transfer in human skeletal muscle , 2003, European journal of clinical investigation.

[8]  L. Strindberg,et al.  Direct measurements of the permeability surface area for insulin and glucose in human skeletal muscle. , 2003, The Journal of clinical endocrinology and metabolism.

[9]  B Thorsteinsson Kinetic models for insulin disappearance from plasma in man. , 1990, Danish medical bulletin.

[10]  Bart De Moor,et al.  A minimal model for glycemia control in critically ill patients , 2006, 2006 International Conference of the IEEE Engineering in Medicine and Biology Society.

[11]  A. Guyton,et al.  Textbook of Medical Physiology , 1961 .

[12]  R. Hovorka,et al.  A simulation model of glucose regulation in the critically ill , 2008, Physiological measurement.

[13]  Christopher E. Hann,et al.  A physiological Intensive Control Insulin-Nutrition-Glucose (ICING) model validated in critically ill patients , 2011, Comput. Methods Programs Biomed..

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

[15]  Thomas Desaive,et al.  Pilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control , 2011, Annals of intensive care.

[16]  Christopher E. Hann,et al.  Tight glycemic control in critical care - The leading role of insulin sensitivity and patient variability: A review and model-based analysis , 2011, Comput. Methods Programs Biomed..

[17]  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.

[18]  Christopher E. Hann,et al.  Monte Carlo analysis of a new model-based method for insulin sensitivity testing , 2008, Comput. Methods Programs Biomed..

[19]  Steen Andreassen,et al.  A simulation model of insulin saturation and glucose balance for glycemic control in ICU patients , 2010, Comput. Methods Programs Biomed..

[20]  A. Valerio,et al.  A Circulatory Model for the Estimation of Insulin Sensitivity , 1997 .

[21]  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.

[22]  U. Smith,et al.  Measurement by Microdialysis of the Insulin Concentration in Subcutaneous Interstitial Fluid: Importance of the Endothelial Barrier for Insulin , 1993, Diabetes.