A SIMPLE METHOD FOR QUANTITATION OF INSULIN SENSITIVITY AND INSULIN RELEASE FROM AN INTRAVENOUS GLUCOSE-TOLERANCE TEST

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (K(g)) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (r(s) = 0.89 and r(s) = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states. Insulin sensitivity measured by the shortened 40 min IVGTT and glucose clamp techniques were also comparable for the whole group (r(s) = 0.85), and for hypoinsulinaemic-glucose intolerance subjects (r(s) = 0.96). It is concluded that the shortened simple IVGTT method is practical, gives reliable simultaneous estimates of glucose tolerance, first phase insulin secretion and insulin sensitivity in a diverse group of individuals with normal to moderately impaired glucose tolerance, and therefore may be useful in population surveys where prolonged, multiple blood sampling test procedures are not possible.