A New Index of Insulin Sensitivity from Glucose Sensor and Insulin Pump Data: In Silico and In Vivo Validation in Youths with Type 1 Diabetes

Background: Estimation of insulin sensitivity (S-I) and its daily variation are key for optimizing insulin therapy in patients with type 1 diabetes (T1D). We recently developed a method for S-I estimation from continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) data in adults with T1D (S-I(SP)) and validated it under restrained experimental conditions. Herein, we validate in vivo a new version of S-I(SP) performing well in daily life unrestrained conditions.Methods: The new S-I(SP) was tested in both simulated and real data. The simulated dataset consists of 100 virtual adults of the UVa/Padova T1D Simulator monitored during an open-loop experiment, whereas the real dataset consists of 10 youths with T1D monitored during a hybrid closed-loop meal study. In both datasets, participants underwent two consecutive meals (breakfast and lunch, at 7 and 11 am) with the same carbohydrate content (70 g). Plasma glucose and insulin were measured during each meal to estimate the oral glucose minimal model S-I (S-I(MM)). CGM and CSII data were used for S-I(SP) calculation, which was then validated against the gold standard S-I(MM).Results: S-I(SP) was estimated with good precision (median coefficient of variation <20%) in 100% of the real and 91% of the simulated meals. S-I(SP) and S-I(MM) were highly correlated, both in the simulated and real datasets (R = 0.82 and R = 0.83, P < 0.001), and exhibited a similar intraday pattern.Conclusions: S-I(SP) is suitable for estimating S-I in both closed- and open-loop settings, provided that the subject wears a CGM sensor and a subcutaneous insulin pump.