Minimally-Invasive and Efficient Method to Accurately Fit the Bergman Minimal Model to Diabetes Type 2

Introduction: Diabetes mellitus is a global burden that is expected to grow $25\%$ by 2030. This will increase the need for prevention, diagnosis and treatment of diabetes. Animal and individualized in silico models will allow understanding and compensation for inter and intra-individual differences in treatment and management strategies for diabetic patients. The method presented here can advance the concept of personalized medicine.

Methods: Twenty experiments were performed with Sprague-Dawley rats with streptozotocin induced experimental diabetes in which the insulin-glucose response curve was recorded over 60-100 min using only an insulin pump and a percutaneous glucose sensor. The information was used to fit the five-parameter Bergman Minimal Model to the experimental results using a genetic algorithm with a root-mean-squared optimization rule.

Results: The Bergman Minimal Model parameters were estimated with high accuracy, low prediction bias, and low average root-mean-squared error of 15.27 mg/dl glucose.

Conclusions: This study demonstrates a simple method to accurately parameterize the Bergman Minimal Model. We used Sprague-Dawley rats since their physiology is close to that of humans. The parameters can be used to objectively characterize the physiological severity of diabetes. In this way, planned treatments can compensate for natural variations of conditions both inter and intra patients. Changes in parameters indicate the patient's diabetic condition using values of glucose effectiveness ( $S_{\text{G}}=p_1$ ) and insulin sensitivity ( $S_I=p_3/p_2$ ). Quantifying the diabetic patient's condition is consistent with the trend toward personalized medicine. Parameter values can also be used to explain atypical research results of other studies and increase understanding of diabetes.