Design and Clinical Pilot Testing of the Model-Based Dynamic Insulin Sensitivity and Secretion Test (DISST)

Background: Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. Methods: DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Results: Average variability in IS between low and medium dose was 10.3% (p = .50) and between medium and high dose 6.0% (p = .87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. Conclusions: These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS.

[1]  Tracey McLaughlin,et al.  Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals: effect of differences in insulin sensitivity. , 2007, Archives of internal medicine.

[2]  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.

[3]  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.

[4]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[5]  C. Zancanaro,et al.  Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies. , 1989, The Journal of clinical endocrinology and metabolism.

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

[7]  E. Ferrannini,et al.  Insulin resistance is central to the burden of diabetes. , 1997, Diabetes/metabolism reviews.

[8]  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..

[9]  N. Ray,et al.  Economic Consequences of Diabetes Mellitus in the U.S. in 1997 , 1998, Diabetes Care.

[10]  C Cobelli,et al.  Hepatic glucose production during the labeled IVGTT: estimation by deconvolution with a new minimal model. , 1993, The American journal of physiology.

[11]  Geoffrey M Shaw,et al.  Point: HOMA—Satisfactory for the Time Being , 2007, Diabetes Care.

[12]  D A Follmann,et al.  The Journal of Clinical Endocrinology & Metabolism Printed in U.S.A. Copyright © 2000 by The Endocrine Society Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans , 2022 .

[13]  L. Groop,et al.  Studies on the mass action effect of glucose in NIDDM and IDDM: evidence for glucose resistance , 1997, Diabetologia.

[14]  P Wach,et al.  Plasma and interstitial glucose dynamics after intravenous glucose injection: evaluation of the single-compartment glucose distribution assumption in the minimal models. , 1999, Diabetes.

[15]  O. Schmitz,et al.  Acute Pain Induces Insulin Resistance in Humans , 2001, Anesthesiology.

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

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

[18]  C. Kühl,et al.  Insulin bolus given by sprinkler needle: effect on absorption and glycaemic response to a meal. , 1987, British medical journal.

[19]  R N Bergman,et al.  Role of Glucose Effectiveness in the Determination of Glucose Tolerance , 1996, Diabetes Care.

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

[21]  D. O'Gorman,et al.  Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes , 2006, Diabetologia.

[22]  A Mari,et al.  How to measure insulin sensitivity , 1998, Journal of hypertension.

[23]  Richard M Watanabe,et al.  A Comparison Between the Minimal Model and the Glucose Clamp in the Assessment of Insulin Sensitivity Across the Spectrum of Glucose Tolerance , 1994, Diabetes.

[24]  R. N. Bergman,et al.  Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study , 1992, The Lancet.

[25]  R. Rizza,et al.  Glucose-induced suppression of endogenous glucose production: dynamic response to differing glucose profiles. , 2003, American journal of physiology. Endocrinology and metabolism.

[26]  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.

[27]  Claudio Cobelli,et al.  A minimal model of insulin secretion and kinetics to assess hepatic insulin extraction. , 2006, American journal of physiology. Endocrinology and metabolism.

[28]  Claudio Cobelli,et al.  Bayesian two-compartment and classic single-compartment minimal models: Comparison on insulin modified IVGTT and effect of experiment reduction , 2003, IEEE Transactions on Biomedical Engineering.

[29]  N. Paquot,et al.  How to measure insulin action in vivo. , 1994, Diabetes/metabolism reviews.

[30]  Paolo Vicini,et al.  Population approaches to estimate minimal model indexes of insulin sensitivity and glucose effectiveness using full and reduced sampling schedules. , 2006, American journal of physiology. Endocrinology and metabolism.

[31]  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.

[32]  C. Homko,et al.  Methods of Measuring Insulin Sensitivity , 2007, Biological research for nursing.

[33]  M Kieser,et al.  Sample size determination for proving equivalence based on the ratio of two means for normally distributed data. , 1999, Statistics in medicine.

[34]  R. DeFronzo,et al.  Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease , 1991, Diabetes Care.

[35]  M. Quon,et al.  Non-Insulin-Mediated Glucose Disappearance in Subjects With IDDM: Discordance Between Experimental Results and Minimal Model Analysis , 1994, Diabetes.

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

[37]  C Cobelli,et al.  Estimation of insulin sensitivity and glucose clearance from minimal model: new insights from labeled IVGTT. , 1986, The American journal of physiology.

[38]  G. Reaven,et al.  Treatment of Patients with Non‐insulin‐dependent Diabetes Mellitus: Diabetic Control and Insulin Secretion and Action After Different Treatment Modalities , 1987, Diabetic medicine : a journal of the British Diabetic Association.

[39]  Scott K Aberegg,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[40]  R N Bergman,et al.  MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. , 1986, Computer methods and programs in biomedicine.

[41]  Christopher E. Hann,et al.  Model-based glycaemic control in critical care - A review of the state of the possible , 2006, Biomed. Signal Process. Control..

[42]  T. Lotz,et al.  High Resolution Clinical Model-Based Assessment of Insulin Sensitivity , 2007 .

[43]  R. DeFronzo,et al.  Splanchnic and renal metabolism of insulin in human subjects: a dose-response study. , 1983, The American journal of physiology.

[44]  P. Lönnroth,et al.  Measurement of interstitial insulin in human muscle. , 1999, The American journal of physiology.

[45]  Giovanni Sparacino,et al.  Minimal model S(I)=0 problem in NIDDM subjects: nonzero Bayesian estimates with credible confidence intervals. , 2002, American journal of physiology. Endocrinology and metabolism.

[46]  A. Vaag,et al.  A Simple Method for Quantitation of Insulin Sensitivity and Insulin Release from an Intravenous Glucose Tolerance Test , 1992, Diabetic medicine : a journal of the British Diabetic Association.

[47]  J. Radziuk,et al.  Insulin sensitivity and its measurement: structural commonalities among the methods. , 2000, The Journal of clinical endocrinology and metabolism.

[48]  A J Scheen,et al.  Roles of circadian rhythmicity and sleep in human glucose regulation. , 1997, Endocrine reviews.

[49]  Christopher E. Hann,et al.  Integral-based identification of a physiological insulin and glucose model on euglycaemic clamp trials and IVGTT trials (Invited) , 2006 .

[50]  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..

[51]  R. Moxley,et al.  Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy. , 1989, Archives of neurology.

[52]  C. Cobelli,et al.  Glucose effectiveness and insulin sensitivity from the minimal models: consequences of undermodeling assessed by Monte Carlo simulation , 1999, IEEE Transactions on Biomedical Engineering.

[53]  Hiroaki Tanaka,et al.  Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model. , 2004, Diabetes.

[54]  C. Cobelli,et al.  Is the minimal model too minimal? , 1996, Diabetologia.

[55]  R. Hovorka,et al.  Partitioning glucose distribution/transport, disposal, and endogenous production during IVGTT. , 2002, American journal of physiology. Endocrinology and metabolism.