In Silico Modeling of Minimal Effective Insulin Doses Using the UVA/PADOVA Type 1 Diabetes Simulator

BACKGROUND: The objective of this study was to identify the minimum basal insulin infusion rates and bolus insulin doses that would result in clinically relevant changes in blood glucose levels in the most insulin sensitive subjects with type 1 diabetes. METHODS: The UVA/PADOVA Type 1 Diabetes Simulator in silico population of children, adolescents, and adults was administered a basal insulin infusion rate to maintain blood glucose concentrations at 120 mg/dL (6.7 mmol/L). Two scenarios were modeled independently after 1 hour of simulated time: (1) basal insulin infusion rates in increments of 0.01 U/h were administered and (2) bolus doses in increments of 0.01 U were injected. Subjects were observed for 4 hours to determine insulin delivery required to change blood glucose by 12.5 mg/dL (0.7 mmol/L) and 25 mg/dL (1.4 mmol/L) in only 5% of the in silico population. RESULTS: The basal insulin infusion rates required to change blood glucose by 12.5 mg/dL and 25 mg/dL in 5% of children, adolescents, and adults were 0.03, 0.11, and 0.10 U/h and 0.06, 0.21, and 0.19 U/h, respectively. The bolus insulin doses required to change blood glucose by the target amounts in the respective populations were 0.10, 0.28, and 0.30 U and 0.19, 0.55, and 0.60 U. CONCLUSIONS: In silico modeling suggests that only a very small percentage of individuals with type 1 diabetes, corresponding to children with high insulin sensitivity and low body weight, will exhibit a clinically relevant change in blood glucose with very low basal insulin rate changes or bolus doses.