Modeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp

Dalla Man C, Piccinini F, Basu R, Basu A, Rizza RA, Cobelli C. Modeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp. Am J Physiol Endocrinol Metab 304: E819-E825, 2013. First published February 26, 2013; doi:10.1152/ajpendo.00482.2012.-Recently, we proposed a model describing the suppression of endogenous glucose production (EGP) during a meal. It assumes that EGP suppression depends on glucose concentration and its rate of change and on delayed insulin action. Hepatic insulin sensitivity (S-I(Lmeal)) can be derived from EGP model parameters. This model was shown to adequately describe EGP profiles measured with multiple tracer techniques; however, S-I(Lmeal) has never been compared directly with its euglycemic hyperinsulinemic clamp counterpart (S-I(Lclamp)). To do so, 62 subjects with different degrees of glucose tolerance underwent a triple-tracer mixed meal. Fifty-seven subjects also underwent a labeled ([3-H-3]glucose) euglycemic hyperinsulinemic clamp. From the triple-tracer meal data, virtually model-independent estimates of EGP were obtained using the tracer-to-tracee clamp technique, and the EGP model was identified in each subject. Model fit was satisfactory, and S-I(Lmeal) was estimated with good precision. Correlation between S-I(Lclamp) and S-I(Lmeal) was good (r = 0.72, P < 0.001); however, S-I(Lmeal) was lower than S-I(Lclamp) (4.60 +/- 0.64 vs. 8.73 +/- 1.07 10(-4) dl.kg(-1).min(-1) per mu U/ml, P < 0.01). This difference may be due to different ranges of insulin explored during the two tests (Delta I-clamp = 15.60 +/- 1.61 vs. Delta I-meal = 83.37 +/- 10.71 mu U/ml) as well as steady- vs. non-steady-state glucose and insulin profiles. In conclusion, the new EGP model provides an estimate of hepatic insulin sensitivity during a meal that is in good agreement with that derived in the same individuals with a hyperinsulinemic clamp. When used in conjunction with the minimal model, the approach potentially enables estimation of hepatic insulin sensitivity from a single-tracer labeled meal or oral glucose tolerance test.