The Identifiable Virtual Patient Model: Comparison of Simulation and Clinical Closed-Loop Study Results

• Published in: Journal of diabetes science and technology Vol. 6; no. 2; pp. 371 - 379
• Main Authors: Kanderian, Sami S., Weinzimer, Stuart A., Steil, Garry M.
• Format: Journal Article
• Language: English
• Published: United States Diabetes Technology Society 01.03.2012
• Subjects: Adolescent; Adult; Algorithms; Analysis of Variance; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Chi-Square Distribution; Computer Simulation; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Dietary Carbohydrates - administration & dosage; Eating; Fasting - blood; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemia - chemically induced; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - blood; Insulin - administration & dosage; Insulin - adverse effects; Insulin - blood; Insulin Infusion Systems; Middle Aged; Models, Biological; Original; Patient Simulation; Postprandial Period; Reproducibility of Results; Time Factors
• ISSN: 1932-2968; 1932-3107
• DOI: 10.1177/193229681200600223

Optimizing a closed-loop insulin delivery algorithm for individuals with type 1 diabetes can be potentially facilitated by a mathematical model of the patient. However, model simulation studies that evaluate changes to the control algorithm need to produce conclusions similar to those that would be obtained from a clinical study evaluating the same modification. We evaluated the ability of a low-order identifiable virtual patient (IVP) model to achieve this goal. Ten adult subjects (42.5 ± 11.5 years of age; 18.0 ± 13.5 years diabetes; 6.9 ± 0.8% hemoglobin A1c) previously characterized with the IVP model were studied following the procedures independently reported in a pediatric study assessing proportional-integral-derivative control with and without a 50% meal insulin bolus. Peak postprandial glucose levels with and without the meal bolus and use of supplemental carbohydrate to treat hypoglycemia were compared using two-way analysis of variance and chi-square tests, respectively. The meal bolus decreased the peak postprandial glucose levels in both the adult-simulation and pediatricclinical study (231 ± 38 standard deviation to 205 ± 33 mg/dl and 226 ± 51 to 194 ± 47 mg/dl, respectively; p = .0472). No differences were observed between the peak postprandial levels obtained in the two studies (clinical and simulation study not different, p = .57; interaction p = .83) or in the use of supplemental carbohydrate (3 occurrences in 17 patient days of closed-loop control in the clinical-pediatric study; 7 occurrences over 20 patient days in the adult-simulation study, p = .29). Closed-loop simulations using an IVP model can predict clinical study outcomes in patients studied independently from those used to develop the model.