Predictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity

Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated.

In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m²) with varying degrees of glucose tolerance. A calibration model was used to assess the ability of OGTT-derived, tissue-specific surrogate indices [hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI)] to predict insulin sensitivity/resistance indices derived from the reference glucose clamp [Hepatic-IR_basal, a product of fasting plasma insulin and hepatic glucose production (HGP), Hepatic-IR_clamp, reciprocal of the percent suppression of HGP during the insulin clamp corrected for plasma insulin concentration, and Muscle-IS_clamp, a measure of peripheral glucose disposal]. Predictive accuracy was assessed by root mean squared error of prediction and leave-one-out, cross-validation-type square root of the mean squared error of prediction.

HIRI and MISI were correlated with their respective clamp-derived indices. HIRI was negatively related to Muscle-IS_clamp (r = -0.62, P < 0.0001) and MISI correlated with Hepatic-IR derived from the clamp (Hepatic-IR_basal: r = -0.48, P < 0.0001 and Hepatic-IR_clamp: r = -0.41, P < 0.0001). However, the accuracy of HIRI and MISI to predict Hepatic-IR (basal or during clamp) was not significantly different. Likewise, the ability of HIRI and MISI to predict Muscle-IS_clamp was also similar.

Our findings indicate that the surrogate indices derived from an OGTT are accurate in predicting insulin sensitivity but are not tissue specific.