Repeatability characteristics of simple indices of insulin resistance: Implications for research applications

The objectives of this study were to evaluate test characteristics, such as normality of distribution, variation, and repeatability, of simple fasting measures of insulin sensitivity and to use the results to choose among the se measures. Duplicate fasting samples of insulin and glucose were collecte d before 4 h of euglycemic hyperinsulinemic clamping using insulin infusion rates ranging from 40-600 mU/m(2.)min. Currently recommended estimates of insulin sensitivity, including the fasting insulin, 40/insulin, the homeost asis model assessment, the logarithmic transformation of the homeostasis mo del assessment, and the Quantitative Insulin Sensitivity Check Index, were evaluated. The normality of distribution and the variability of the tests ( coefficient of variation and discriminant ratio) were compared between the measures and against the "gold standard" hyperinsulinemic clamp. Data from 253 clamp studies in 152 subjects were examined, including 79 repeated stud ies for repeatability analysis. In subjects ranging from lean to diabetic, the log transformed fasting measures combining insulin and glucose had norm al distributions and test characteristics superior to the stasis model asse ssment coefficient of variation, 0.55; discriminant ratio, 13; Quantitative Insulin Sensitivity Check Index coefficient of variation, 0.05; discrimina nt ratio, 10) and statistically comparable to euglycemic hyperinsulinemic c lamps (coefficient of variation, 0.10; discriminant ratio, 6.4). These favo rable characteristics helped explain the superior correlations of these mea sures with the hyperinsulinemic clamps among insulin-resistant subjects. Fu rthermore, therapeutic changes in insulin sensitivity were as readily demon strated with these simple measures as with the hyperinsulinemic clamp. The test characteristics of the logarithmic transformation of the homeostasis m odel assessment and the Quantitative Insulin Sensitivity Check Index are su perior to other simple indices of insulin sensitivity. This helps explain t heir excellent correlations with formal measures both at baseline and with changes in insulin sensitivity and supports their broader application in cl inical research.