Relationship between several surrogate estimates of insulin resistance andquantification of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers

OBJECTIVE - The goal of this study was to define the relationship between a quantitative measure of the ability of physiological hyperinsulinemia to s timulate glucose disposal and several surrogate measures of insulin resista nce. RESEARCH DESIGN AND METHODS - insulin-mediated glucose disposal was quantif ied in 490 healthy nondiabetic volunteers by determining the steady-state p lasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose: Because the steady-state plasma insulin concentration was similar in all subjects during the infusion (similar to 60 mu U/ml), the SSPG concentration provided a direct estimate of insulin-m ediated glucose disposal. Relationships between this specific measure of in sulin resistance and several surrogate estimates of insulin resistance base d on plasma glucose and insulin concentrations were then defined. RESULTS - The surrogate measure of insulin resistance most closely related to the direct determination of insulin action was the total integrated insu lin response to a 75-g oral glucose challenge with correlation coefficients (r) varying from 0.67 to 0.79. Fasting plasma insulin concentration was si gnificantly correlated (r = 0.61, P < 0.001) to the specific estimate of in sulin action. Two other surrogate estimates of insulin action, the ratio of fasting glucose-to-fasting insulin concentration and the homeostasis model assessment for insulin resistance, were no more closely related to SSPG th an the fasting plasma insulin concentration. CONCLUSIONS - The total integrated insulin response to oral glucose is the best surrogate measure of insulin resistance, accounting for approximately two-thirds of the variability in insulin-mediated glucose disposal. Fasting insulin concentration accounted for approximately one-third of the variabi lity in insulin-mediated glucose disposal, and the use of fasting plasma gl ucose and insulin concentrations to calculate more sophisticated estimates of insulin resistance appears to offer little advantage over the fasting pl asma insulin concentration. Given the large number of nondiabetic individua ls in this study: the results should have general application in population -based studies, providing evidence for both the utility and limitation of t he use of these surrogate measures.