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Derivation of a quantitative measure of insulin sensitivity from the intravenous tolbutamide test using the minimal model of glucose dynamics

1987; Springer Science+Business Media; Volume: 30; Issue: 5 Linguagem: Inglês

10.1007/bf00299024

1432-0428

N. M. Shennan, IF Godsland, V. Wynn,

Pharmacology and Obesity Treatment

Using the decay phase of the glucose response during an intravenous tolbutamide test, a minimal model of glucose dynamics was used to calculate a value for an “index of insulin sensitivity”. This index describes the efficiency of insulin in accelerating the instantaneous rate of glucose disposal, and provides a measure of insulin resistance. The validity of estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test have been assessed with reference to estimates of this index derived from the intravenous glucose tolerance test for which the model was originally designed. There were three studies: (A) estimates of the index of insulin sensitivity obtained from the intravenous tolbutamide test in a group of normal, healthy men and women were compared with results obtained in a comparable group of subjects using the intravenous glucose tolerance test. The two methods gave estimates of the index of insulin sensitivity that were identical; (B) A group of patients taking methandienone, an anabolic steroid previously shown to cause marked insulin resistance, were tested whilst taking the steroid and either before, or at least two months after treatment. Each patient was tested by both intravenous tolbutamide test and intravenous glucose tolerance test on both occasions. Estimates of the index of insulin sensitivity from intravenous glucose tolerance or intravenous tolbutamide procedures both on and off treatment were significantly correlated (off treatment: r s ,= 0.71, n=9, p<0.05; on treatment: r s =0.69, n=9, p<0.05); (C) A group of patients undergoing investigations for suspected disturbances in carbohydrate metabolism was studied, each patient having had both an intravenous tolbutamide and intravenous glucose tolerance test. The group studied included patients in whom a degree of insulin resistance would be expected. Estimates of the index of insulin sensitivity from the two methods were closely correlated (r s =0.95, n=25, p<0.001). This strong, identical correlation obtained between the intravenous glucose tolerance and intravenous tolbutamide tolerance estimates of index of insulin sensitivity in studies B and C over a wide range of values [intravenous tolbutamide tolerance test: 0.11–1.07 min−1U−1 1; intravenous glucose tolerance test: 0.12-1.06 min−1U−11]. This suggests that the intravenous tolbutamide estimates of index of insulin sensitivity are closely comparable to those derived from intravenous glucose tolerance test over a broad range of insulin sensitivities. We suggest that the use of intravenous tolbutamide to induce a dynamic change in insulin-glucose relationships, and mathematical modelling of those dynamics, can provide a valuable, quantitative measure of insulin sensitivity in a variety of clinical situations.