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Insulin sensitivity by oral glucose minimal models: validation against clamp

¹Department of Information Engineering, University of Padova, Padua, Italy; ²Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri; and ³San Raffaele Scientific Institute, Milan, Italy

Submitted 22 February 2005 ; accepted in final form 10 July 2005

Measuring insulin sensitivity in the presence of physiological changes in glucose and insulin concentrations, e.g., during a meal or OGTT, is important to better understand insulin resistance in a variety of metabolic conditions. Recently, two oral minimal models have been proposed to measure overall insulin sensitivity (S_I) and its selective effect on glucose disposal (S_I*) from oral tests. S_I and S_I* have been successfully validated against multiple tracer meal estimates, but validation against euglycemic hyperinsulinemic clamp estimates is lacking. Here, we do so in 21 subjects who underwent both a multiple-tracer OGTT and a labeled euglycemic hyperinsulinemic clamp. Correlation between minimal-model S_I, S_I and corresponding clamp estimates S_I^*clamp, S_I^*clamp was satisfactory, respectively r = 0.81, P < 0.001, and r = 0.71, P < 0.001. S_I was significantly lower than S_I^clamp (8.08 ± 0.89 vs. 13.66 ± 1.69 10^–4 dl·kg^–1·min^–1 per µU/ml, P = 0.0002), whereas S_I and S_I^*clamp were very similar (8.17 ± 1.59 vs. 8.84 ± 1.39 10^–4 dl·kg^–1·min^–1 per µU/ml, P = 0.52). These results add credibility to the oral minimal-model method as a simple and reliable physiological tool to estimate S_I and S_I*, also in large-scale clinical trials.

insulin resistance; oral glucose tolerance test; meal; insulin action; tracer kinetics

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