Model-based subcutaneous insulin for glycemic control of pre-term infants in the neonatal intensive care unit

Hyperglycaemia is a common problem in neonatal intensive care units (NICUs). Achieving good control can result in better outcomes for patients. However, good control is difficult, where poor control and resulting hypoglycaemia reduces outcomes and confounds results. Clinically validated models can provide good control, and subcutaneous insulin delivery can provide more options for insulin therapy for clinicians. However, this combination has only been significantly utilised in adult outpatient diabetes, but could hold benefit for treating NICU infants. This research combines a well-validated NICU metabolic model with subcutaneous insulin kinetics models to assess the feasibility of a model-based approach. Clinical data from 12 very/extremely pre-mature infants was collected for an average study duration of 10.1 days. Blood glucose, interstitial and plasma insulin, as well as subcutaneous and local insulin were modelled, and patient-specific insulin sensitivity profiles were identified for each patient. Modelling error was low, where the cohort median [IQR] mean percentage error was 0.8 [0.3 3.4] %. For external validation, insulin sensitivity was compared to previous NICU cohorts using the same metabolic model, where overall levels of insulin sensitivity were similar. Overall, the combined system model accurately captured observed glucose and insulin dynamics, showing the potential for a model-based approach to glycaemic control using subcutaneous insulin in this cohort. The results justify further model validation and clinical trial research to explore a model-based protocol.