Choosing an optimal input for an intravenous glucose tolerance test to aid parameter identification

The minimal model is used to estimate insulin sensitivity in patients with diabetes, following an intravenous glucose tolerance test (IVGTT). Issues have been reported regarding parameter estimation, including correlation between insulin sensitivity and action parameters. The objective was to reduce these issues, by modifying the input of glucose in the test.

Data were available for 24 volunteers following an IVGTT and glucose clamp test. Correlation between parameters was explored using likelihood heatmaps. An integrated glucose-insulin model was used to simulate glucose and insulin concentrations following new glucose inputs. The improved input for the test was selected by finding the minimum inverse of the determinant of the Fisher information matrix.

When the minimal model was fitted to the IVGTT data, there was clear correlation between the insulin parameters. With the glucose clamp, all parameters were correlated and badly estimated. The modified input, a bolus dose followed by constant infusion, resulted in improvement in parameter estimation and reduction in parameter correlation.

It is possible to reduce the issues with parameter estimation in the minimal model by modifying the glucose input, leading to a simplified test deign and a reduction in the total amount of glucose infused.