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A Modified Protocol for Estimation of Insulin Sensitivity with the Minimal Model of Glucose Kinetics in Patients with Insulin-Dependent Diabetes^*

Departments of Medicine and Physiology, University of Alberta Edmonton, Alberta; Canada
The Department of Medicine, University of Western Ontario (I.M.H., J.D.) London, Ontario, Canada

Address all correspondence and requests for reprints to: Diane T. Finegood, Ph.D., Department of Medicine, Division of Endocrinology and Metabolism, 7-117J Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada.

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 (S_I) and glucose effectiveness (S_G) 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. S_I and S_G were not different for the insulin infusionand tolbutamide-modified protocols [S_I, 2.8 ± 0.4, 3.6 ± 0.6, and 2.5 ± 0.5 x 10⁴ min¹(µU/mL), respectively].

S_I and S_G were quantified in insulin-requiring newly diagnosed IDDM and in noninsulin-requiring IDDM in clinical remission with the exogenous insulin administration protocol. Both S_I and S_G were reduced in newly diagnosed IDDM compared to normal controls (by 64% and 40%, respectively). S_I was normalized in IDDM in clinical remission despite a continued poor insulin secretory response to both glucose and tolbutamide. Although S_I was normal in patients in clinical remission, S_G 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.

^* This work was supported by grants from the Juvenile Diabetes Foundation (no. 187501. and the Alberta Heritage Foundation for Medical Research.

Received May 22, 1989.

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