Titration of Long-Acting Insulin Using Continuous Glucose Monitoring and Smart Insulin Pens in Type 1 Diabetes: A Model-Based Carbohydrate-Free Approach

Multiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D), consisting of long-acting insulin to cover fasting conditions and rapid-acting insulin to cover meals. Titration of long-acting insulin is needed to achieve satisfactory glycemia but is challenging due to inter-and intra-individual metabolic variability. In this work, a novel titration algorithm for long-acting insulin leveraging continuous glucose monitoring (CGM) and smart insulin pens (SIP) data is proposed. The algorithm is based on a glucoregulatory model that describes insulin and meal effects on blood glucose fluctuations. The model is individualized on patient's data and used to extract the theoretical glucose curve in fasting conditions; the individualization step does not require any carbohydrate records. A cost function is employed to search for the optimal long-acting insulin dose to achieve the desired glycemic target in the fasting state. The algorithm was tested in two virtual studies performed within a validated T1D simulation platform, deploying different levels of metabolic variability (nominal and variance). The performance of the method was compared to that achieved with two published titration algorithms based on self-measured blood glucose (SMBG) records. The sensitivity of the algorithm to carbohydrate records was also analyzed. The proposed method outperformed SMBG-based methods in terms of reduction of exposure to hypoglycemia, especially during the night period (0 am-6 am). In the variance scenario, during the night, an improvement in the time in the target glycemic range (70-180 mg/dL) from 69.0% to 86.4% and a decrease in the time in hypoglycemia (