Independent cohort cross-validation of the real-time DISTq estimation of insulin sensitivity

Insulin sensitivity (SI) is useful in the diagnosis, screening and treatment of diabetes. However, most current tests cannot provide an accurate, immediate or real-time estimate. The DISTq method does not require insulin or C-peptide assays like most SI tests, thus enabling real-time, low-cost SI estimation. The method uses a posteriori parameter estimations in the absence of insulin or C-peptide assays to simulate accurate, patient-specific, insulin concentrations that enable SI identification. Mathematical functions for the a posteriori parameter estimates were generated using data from 46 fully sampled DIST tests (glucose, insulin and C-peptide). SI values found using the DISTq from the 46 test pilot cohort and a second independent 218 test cohort correlated R=0.890 and R=0.825, respectively, to the fully sampled (including insulin and C-peptide assays) DIST SI metrics. When the a posteriori insulin estimation functions were derived using the second cohort, correlations for the pilot and second cohorts reduced to 0.765 and 0.818, respectively. These results show accurate SI estimation is possible in the absence of insulin or C-peptide assays using the proposed method. Such estimates may only need to be generated once and then used repeatedly in the future for isolated cohorts. The reduced correlation using the second cohort was due to this cohort's bias towards low SI insulin resistant subjects, limiting the data set's ability to generalise over a wider range. All the correlations remain high enough for the DISTq to be a useful test for a number of clinical applications. The unique real-time results can be generated within minutes of testing as no insulin and C-peptide assays are required and may enable new clinical applications.

[1]  M. Matsuda,et al.  Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. , 1999, Diabetes care.

[2]  Christopher E. Hann,et al.  Model-Based Insulin Sensitivity as a Sepsis Diagnostic in Critical Care , 2008, Journal of diabetes science and technology.

[3]  M. Matsuda,et al.  Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study , 2003, Diabetologia.

[4]  Wolfgang Dietrich,et al.  Are there time and cost savings by using telemanagement for patients on intensified insulin therapy?: A randomised, controlled trial , 2002, Comput. Methods Programs Biomed..

[5]  R. Morris,et al.  Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance. , 1999, The American journal of physiology.

[6]  Andrea Mari,et al.  Methods for clinical assessment of insulin sensitivity and β-cell function , 2003 .

[7]  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.

[8]  Johannes D Veldhuis,et al.  Pulsatile insulin secretion dictates systemic insulin delivery by regulating hepatic insulin extraction in humans. , 2005, Diabetes.

[9]  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.

[10]  H. Lithell,et al.  Risk factors for developing non-insulin dependent diabetes: a 10 year follow up of men in Uppsala. , 1991, BMJ.

[11]  N. Schneiderman,et al.  Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures. , 2000, Diabetes research and clinical practice.

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

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

[14]  N J Wareham,et al.  The effect of varying the screening interval on false positives and duration of undiagnosed disease in a screening programme for type 2 diabetes , 2000, Journal of medical screening.

[15]  Andrew J Karter,et al.  Insulin resistance, beta-cell dysfunction, and conversion to type 2 diabetes in a multiethnic population: the Insulin Resistance Atherosclerosis Study. , 2010, Diabetes care.

[16]  M Tominaga,et al.  [Diagnostic criteria for diabetes mellitus]. , 1999, Rinsho byori. The Japanese journal of clinical pathology.

[17]  Neil Salkind Encyclopedia of Measurement and Statistics , 2006 .

[18]  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.

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

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

[21]  J. Geoffrey Chase,et al.  DISTq: An Iterative Analysis of Glucose Data for Low-Cost, Real-Time and Accurate Estimation of Insulin Sensitivity , 2009, The open medical informatics journal.

[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]  M. Matsuda,et al.  Reply to Comment on: Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA (2004) Beta cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia 43:31–39 , 2004, Diabetologia.

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

[25]  J. Chan,et al.  The Reproducibility and Usefulness of the Oral Glucose Tolerance Test in Screening for Diabetes and other Cardiovascular Risk Factors , 1998, Annals of clinical biochemistry.

[26]  P. Raina,et al.  Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. , 2005, Evidence report/technology assessment.

[27]  M. Stumvoll,et al.  Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. , 2000, Diabetes care.

[28]  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..

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

[30]  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.

[31]  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.

[32]  E. Bonora,et al.  Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , 2000, Diabetes care.

[33]  Andrea Mari,et al.  Methods for clinical assessment of insulin sensitivity and beta-cell function. , 2003, Best practice & research. Clinical endocrinology & metabolism.

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

[35]  Andrea Mari,et al.  A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test , 2001 .

[36]  Ra De Fronzo Glucose clamp technique : A method for quantifying insulin secretion and resistance , 1979 .

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

[38]  Lorraine Avery,et al.  Effects of a tailored lifestyle self-management intervention in patients with type 2 diabetes. , 2004, British journal of health psychology.

[39]  G. Guyatt,et al.  Telecare for patients with type 1 diabetes and inadequate glycemic control: a randomized controlled trial and meta-analysis. , 2004, Diabetes care.

[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]  J. Cederholm,et al.  Insulin release and peripheral sensitivity at the oral glucose tolerance test. , 1990, Diabetes research and clinical practice.