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Validation of a new test for insulin sensitivity

Researcher profiles:
Professor Jim Mann

Insulin resistance is a major risk factor for type 2 diabetes and heart disease. Currently the most accurate methods for measuring insulin sensitivity are the 'gold-standard' euglycaemic clamp and the intravenous glucose tolerance test, which are complicated and expensive and can only be used in small research trials. For larger population-based studies crude surrogates are available to measure insulin sensitivity (most are based on fasting insulin and glucose).

We propose a new, dynamic, 30-minute test developed from our clinical model-based glucose and insulin control trials. This model's clinical accuracy is vastly superior to those described previously and has been compared (under simulated conditions) with 146 euglycaemic clamp tests, where it has performed remarkably well.

Novel test challenges the gold standard

We are currently validating this novel test against the gold standard euglycaemic clamp test in a new population. If this test proves to be easy to perform and relatively inexpensive and reliable, it could be used in large research studies of individuals at high risk of diabetes and cardiovascular disease. We believe the proposed test could potentially be used in clinical practice and would be of major international importance given the increasing numbers of individuals at risk of diabetes and heart disease.

This project is a collaboration with winners of the 2006 Health Innovation Awards Supreme Award:

Recent results may enable new clinical applications

Our 2011 publication's results show accurate insulin sensitivity (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 in this study 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.

Publications

Docherty, P.D., Chase, J.G., Lotz, T.F., Hann, C.E., Shaw, G.M., Berkeley. J.E., Mann, J.I., McAuley, K. (2011). Independent cohort cross-validation of the real-time DISTq estimation of insulin sensitivity. Computer Methods and Programs in Biomedicine, 102(2), 94-104 (invited)
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Lotz, T.F., Chase, J.G., McAuley, K.A., Shaw, G.M., Dicherty, P.D., Berekley, J.E., Williams, S.M., Hann, C.E., Mann, J.I. (2010).Design and Clinical Pilot Testing of the Model-Based Dynamic Insulin Sensitivity and Secretion Test (DISST). Journal of Diabetes Science and Technology 4(6), 1408-1423.
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Chase, J.G., Mayntzhusen, K., Docherty, P.D., Andreassen, S., McAuley, K.A., Lotz, T.F., Hann, C.E. (2010). A three-compartment model of the C-peptide-insulin dynamic during the DIST test. Mathematical Biosciences, 228(2), 136-146.
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Chase, J.G., Andreassen, S., Pielmeier, U., Hann, C.E., McAuley, K.A. and Mann, J.I. (2009). A glucose-insulin pharmacodynamic surface modeling validation and comparison of metabolic system models. Biomedical Signal Processing & Control, 4(4), 355-63.

Docherty, P.D., Chase, J.G., Lotz, T., Hann, C.E., Shaw, G.M., Berkeley, J.E., Mann, J.I., McAuley, K. (2009). DISTq: An Iterative Analysis of Glucose Data for Low-Cost, Real-Time and Accurate Estimation of Insulin Sensitivity. Open Med Inform J. 3: 65-76.
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Lotz, T.F., Chase, J.G., McAuley, K.A., Shaw, G.M., Wong, X.W., Lin, J., Lecompte, A., Hann, C.E., Mann, J.I. (2008). Monte Carlo analysis of a new model-based method for insulin sensitivity testing. Computer Methods and Programs in Biomedicine, 89(3), 215-25.
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McAuley, K.A., Mann, J.I., Chase, J.G., Lotz, T.F., Shaw, G.M.(2007). Point: HOMA - Satisfactory for the time being. HOMA: The best bet for the simple determination of insulin sensitivity, until something better comes along. Diabetes Care, 30(9), 2411-2413.

Lotz, T.F., Chase, J.G., Shaw, G.M., McAuley, K.A., Wong, X.W., Lin, J., LeCompte, A., Hann, C.E., Mann, J.I. (2006). Monte Carlo analysis of a new model-based method for insulin sensitivity testing. Computer Methods and Programs in Biomedicine. Submitted 17 July 2006, to appear, ISSN: 0169-2607.

Lotz, T., Chase, J., McAuley, K., Lee, D., Lin, J., Hann, C. and Mann, J.I. (2006). Transient and steady state euglycemic clamp validation of a model for glycemic control and insulin sensitivity testing. Diabetes Technology and Therapeutics, 8(3), 338-346.
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Chase, J.G., Lotz, T., McAuley, K.A., Shaw, G.M., Hann, C.E., Lin, J. and Mann, J.I. (2006). Model-based Assessment of Insulin Resistance in Broad Populations. New Zealand Medical Journal 31 March 2006, Technical Note, Vol 119, No. 1231. Journal is online-only (www.nzma.org.nz). ISSN: 0028-8446.
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