An exogenous insulin administration-modified, frequently sampled iv glucose tolerance test (FSIGT) for application in insulin-dependent diabetic patients (IDDM) to allow for estimation of insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model of glucose kinetics was investigated. An insulin infusion protocol (either 4 or 8 mU/min.kg from 20-25 min) was compared to the standard tolbutamide-modified (300 mg at 20 min) FSIGT in normal control subjects. SI and SG were not different for the insulin infusion- and tolbutamide-modified protocols [SI, 2.8 +/- 0.4, 3.6 +/- 0.6, and 2.5 +/- 0.5 X 10(4) min1/(microU/mL), respectively]. SI and SG were quantified in insulin-requiring newly diagnosed IDDM and in noninsulin-requiring IDDM in clinical remission with the exogenous insulin administration protocol. Both SI and SG were reduced in newly diagnosed IDDM compared to normal controls (by 64% and 40%, respectively). SI was normalized in IDDM in clinical remission despite a continued poor insulin secretory response to both glucose and tolbutamide. Although SI was normal in patients in clinical remission, SG remained reduced (by 65%) compared to that in normal controls. In conclusion, our results demonstrate that modification of the FSIGT with the exogenous administration of insulin allows for estimation of insulin sensitivity and glucose effectiveness in IDDM patients. Comparison to the standard protocol in normal subjects suggests that this results in valid measurements of insulin sensitivity and glucose effectiveness. Results of the application of this protocol in IDDM were consistent with previous observations that insulin sensitivity is reduced in poorly controlled IDDM and normalized in well controlled patients. Glucose effectiveness was found to be reduced in all IDDM subjects regardless of the degree of control.