Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice

Abstract

Insulin resistance contributes to the pathophysiology of diabetes, obesity, and their cardiovascular complications. Mouse models of these human diseases are useful for gaining insight into pathophysiological mechanisms. The reference standard for measuring insulin sensitivity in both humans and animals is the euglycemic glucose clamp. Many studies have compared surrogate indexes of insulin sensitivity and resistance with glucose clamp estimates in humans. However, regulation of metabolic physiology in humans and rodents differs and comparisons between surrogate indexes and the glucose clamp have not been directly evaluated in rodents previously. Therefore, in the present study, we compared glucose clamp-derived measures of insulin sensitivity (GIR and SI(Clamp)) with surrogate indexes, including quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment (HOMA), 1/HOMA, log(HOMA), and 1/fasting insulin, using data from 87 mice with a wide range of insulin sensitivities. We evaluated simple linear correlations and performed calibration model analyses to evaluate the predictive accuracy of each surrogate. All surrogate indexes tested were modestly correlated with both GIR and SI(Clamp). However, a stronger correlation between body weight per se and both GIR and SI(Clamp) was noted. Calibration analyses of surrogate indexes adjusted for body weight demonstrated improved predictive accuracy for GIR [e.g., R = 0.68, for QUICKI and log(HOMA)]. We conclude that linear correlations of surrogate indexes with clamp data and predictive accuracy of surrogate indexes in mice are not as substantial as in humans. This may reflect intrinsic differences between human and rodent physiology as well as increased technical difficulties in performing glucose clamps in mice.

Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse

“…Insulin resistance was calculated by the homeostasis model assessment (HOMA) formula (24). The HOMA of insulin resistance index, as described by Matthews et al (24), is the most easily obtained measurement of insulin resistance and can be used as a reliable surrogate measure of in vivo insulin sensitivity because this method correctly differentiates between insulin sensitivity and insulin resistance (25). HOMA Index was calculated with glucose and insulin concentrations obtained after 5 h of fasting using the following formula: fasting blood glucose (md/dl) × fasting insulin (µU/ ml)/22.5.…”

Relationship between the indexes of insulin resistance and metabolic status in dairy cows during early lactation

“…Surrogate methods are indexes calculated from the basal concentration of insulin, glucose and/or NEFA, and include the following indexes: 1/insulin, insulin:glucose ratio, HOMA (Homeostatic Model Assessment), QUICKI (Quantitative Insulin Sensitivity Check Index) and RQUICKI (Revised Quantitative Insulin Sensitivity Check Index) [4]. Indexes of insulin resistance relevance have been estimated by comparison with results obtained by hyperinsulinemic euglicemic clamp as the golden method for determination of insulin resistance [5].…”

Homeostastic Model Assessment and Insulin Sensitivity/Resistance

“…Largely, they correlate with more detailed indices of S I (clamp, IVGTT) (11)(12)(13)(14) and in some longitudinal studies (15,16), but less so in others (17), and not as well in some populations such as African American men (18) and Asian-Indian men that include a preponderance of lean diabetic patients (19). In animal models, mice (20) and rats (21) do not do so well with HOMA, but rhesus monkeys do better (22). Clearly, there is some diversity.…”