Abstract
Standard insulin therapy to treat type 1 diabetes (T1D) consists of exogenous insulin administration through the subcutaneous (SC) tissue. Despite recent advances in insulin formulations, the SC route still suffers from delays and large inter/intra-subject variability that limiting optimal glucose control. Intraperitoneal (IP) insulin administration, despite its higher invasiveness, was shown to represent a valid alternative to the SC one. To date, no mathematical model describing the absorption and distribution of insulin after IP administration is available. Here, we aim to fill this gap by using data from eight patients with T1D, treated by implanted IP pump, studied in a hospitalized setting, with frequent measurements of plasma insulin and glucose concentration. A battery of models describing insulin kinetics after IP administration were tested. Model comparison and selection were performed based on model ability to predict the data, precision of parameters and parsimony criteria. The selected model assumed that the insulin absorption from the IP space was described by a linear, two-compartment model, coupled with a two-compartment model of whole-body insulin kinetics with hepatic insulin extraction controlled by hepatic insulin. Future developments include model incorporation into the UVa/Padova T1D Simulator for testing open- and closed-loop therapies with IP insulin administration.
Highlights
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of the insulin-secreting pancreatic beta cells, leading to chronic hyperglycemia
SC injections are usually done using insulin pens (Multiple Daily Injection, MDI) or, more recently, insulin pump devices (Continuous Subcutaneous Insulin Infusion, CSII). These tools are coupled with glucose sensing devices, such as Self-Monitoring Blood Glucose (SMBG) or, more recently, Continuous Glucose Monitoring (CGM) systems, helping patients to determine the amount of insulin to be administered to keep blood glucose (BG) in a safe range
We aim to fill this gap exploiting data from a population of eight subjects with T1D treated with an implanted IP insulin pump in a hospitalized setting [13]
Summary
Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of the insulin-secreting pancreatic beta cells, leading to chronic hyperglycemia. A 24/7 management of this disease is needed to keep blood glucose (BG) in the target range (70–180 mg/dL) and prevent diabetes-related long- and short-term complications [1]. The. SC injections are usually done using insulin pens (Multiple Daily Injection, MDI) or, more recently, insulin pump devices (Continuous Subcutaneous Insulin Infusion, CSII). SC injections are usually done using insulin pens (Multiple Daily Injection, MDI) or, more recently, insulin pump devices (Continuous Subcutaneous Insulin Infusion, CSII) These tools are coupled with glucose sensing devices, such as Self-Monitoring Blood Glucose (SMBG) or, more recently, Continuous Glucose Monitoring (CGM) systems, helping patients to determine the amount of insulin to be administered to keep BG in a safe range. Recently CSII and CGM devices have been used, in conjunction with a control algorithm implemented either on a tablet, a smartphone or directly into the pump, to develop a system able to automatically manage insulin dosing, the so-called Artificial
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