Insulin sensitivity by oral glucose minimal models: validation against clamp

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Abstract
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 (SI) and its selective effect on glucose disposal (SI*) from oral tests. SI and SI* 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 SI, SI and corresponding clamp estimates SI*clamp, SI*clamp was satisfactory, respectively r = 0.81, P < 0.001, and r = 0.71, P < 0.001. SI was significantly lower than SIclamp (8.08 ± 0.89 vs. 13.66 ± 1.69 10−4 dl·kg−1·min−1 per μU/ml, P = 0.0002), whereas SI and SI*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 SI and SI*, also in large-scale clinical trials.

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