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Am J Physiol Endocrinol Metab (February 14, 2006). doi:10.1152/ajpendo.00328.2004
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Submitted on July 26, 2004
Accepted on February 5, 2006

Evaluation non-linear regression approaches to estimation of insulin sensitivity by the minimal model with reference to Bayesian hierarchical analysis

Ian F Godsland1*, Olorunsola F Agbaje2, and Roman Hovorka2

1 Faculty of Medicine, Endocrinology and Metabolism, Imperial College London, London, United Kingdom
2 Department of Paediatrics, Diabetes Modelling Group, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: i.godsland{at}imperial.ac.uk.

Minimal model analysis of intravenous glucose tolerance test (IVGTT) glucose and insulin concentrations offers a validated approach to measuring insulin sensitivity, but model identification is not always successful. Improvements may be achieved by using alternative settings in the modelling process, although results may differ according to setting and care must be exercised in combining results. IVGTT data (12 samples, regular test) from 533 men without diabetes was modelled by the traditional non-linear regression (NLR) approach, using 5 different permutations of settings. Results were evaluated with reference to the more robust Bayesian Hierarchical (BH) approach to model identification and to the proportion of variance they explained in known correlates of insulin sensitivity (age, BMI, blood pressure, fasting glucose and insulin, serum triglyceride, HDL cholesterol and uric acid concentration). BH analysis was successful in all cases. With NLR analysis, between 17 and 35 IVGTTs were associated with parameter coefficients of variation (PCVs) for minimal model parameters SI (insulin sensitivity) and SG (glucose effectiveness) of >100%. Systematic use of each different approach in combination reduced this number to 5. Mean (inter-quartile range) SINLR was then 3.14 (2.29-4.63) min-1.mU-1.l x10-4 and 2.56 (1.74-3.83) min-1.mU-1.l x10-4 for SIBH (correlation 0.86, p<0.0001). SINLR explained, on average, 10.6% of the variance in known correlates of insulin sensitivity, whereas SIBH explained 8.5%. In a large body of data, which BH analysis demonstrated could be fully identified, use of alternative modelling settings in NLR analysis could substantially reduce the number of analyses with PCVs>100%. SINLR compared favourably with SIBH in the proportion of variance explained in known correlates of insulin sensitivity.







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