A coordinated control strategy for insulin and glucagon delivery in type 1 diabetes

Type 1 diabetes is an autoimmune condition characterised by a pancreatic insulin secretion deficit, resulting in high blood glucose concentrations, which can lead to micro- and macrovascular complications. Type 1 diabetes also leads to impaired glucagon production by the pancreatic α-cells, which acts as a counter-regulatory hormone to insulin. A closed-loop system for automatic insulin and glucagon delivery, also referred to as an artificial pancreas, has the potential to reduce the self-management burden of type 1 diabetes and reduce the risk of hypo- and hyperglycemia. To date, bihormonal closed-loop systems for glucagon and insulin delivery have been based on two independent controllers. However, in physiology, the secretion of insulin and glucagon in the body is closely interconnected by paracrine and endocrine associations. In this work, we present a novel biologically-inspired glucose control strategy that accounts for such coordination. An in silico study using an FDA-accepted type 1 simulator was performed to evaluate the proposed coordinated control strategy compared to its non-coordinated counterpart, as well as an insulin-only version of the controller. The proposed coordinated strategy achieves a reduction of hyperglycemia without increasing hypoglycemia, when compared to its non-coordinated counterpart

Impact of Sensing and Actuation Characteristics on Artificial Pancreas Design

Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by the body’s inability to produce insulin, leading to chronically high blood glucose (BG) concentrations. T1DM is treated by frequent self-administration of insulin based on BG measurements; however, there is a fine line between too little and too much insulin, and an overdose can lead to a dangerous drop in BG. The artificial pancreas (AP), consisting of a glucose sensor, an insulin pump, and a feedback control algorithm, will replace self-treatment by automatically calculating and delivering insulin dosages based on continuous glucose measurements. Many iterations of the AP utilize commercially available subcutaneous (SC) insulin pumps and glucose sensors, but these devices introduce physiological limitations that make control difficult. In this work, we present a clinical evaluation of an AP that uses SC devices, as well as an investigation of the intraperitoneal (IP) space as an alternative site for insulin delivery and glucose sensing to improve AP performance. Our results show that glucose sensors placed in the IP space have a lower time constant than SC sensors, allowing the controller to respond more quickly to BG disturbances. Similarly, insulin delivered through the IP space has faster pharmacokinetic and pharmacodynamic characteristics than SC insulin. Based on models of the sensing and actuation dynamics, a proportional-integral-derivative control algorithm with anti-reset windup protection was designed for the IP-IP route and evaluated on 10 simulated T1DM subjects. Using the IP-IP route led to a more robust controller that provided excellent control during the simulation studies. Our results support the development of a fully implantable AP that will operate within the IP space to safely and effectively control BG levels