An intraperitoneal artificial pancreas for people with diabetes mimics natural physiology.

What is it about?

Intraperitoneal insulin delivery and glucose sensing, differently from the subcutaneous insulin delivery route, restore natural physiology. In this paper we show the in silico design and validation of an intraperitoneal controller for a fully automated intervention-free personalized artificial pancreas.

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Why is it important?

Over the past decade, the use of automated insulin delivery systems – often referred to as artificial pancreas - have shifted the paradigm treatment in both adults and children: the availability of continuous subcutaneous glucose sensors that guide subcutaneous insulin delivery through control algorithms has allowed, for the first time, to drastically reduce the daily burden of the disease for people with type 1 diabetes and their families, as well as to abate its major short term complications (such as hypoglycemia), while simultaneously reducing the incidence of long-term microvascular complications. The artificial pancreas does not represent a “cure”, and remains a complex instrument that can provide a reasonable improvement in the disease. Additionally, the improvement of glycemic control through subcutaneous insulin delivery does not come without a cost: individuals with type 1 diabetes are exposed to peripheral non-physiologic hyperinsulinemia which over time becomes a major contributor to macrovascular complications, including hearth failure and macrovascular diseases that are still three times more frequent in the patients with type 1 diabetes compared to their healthy peers and are the first cause of mortality, even for those who achieve optimal glycemic control over a lifetime. Subcutaneous insulin delivery creates a paradoxical peripheral hyperinsulinemia necessary to achieve minimal insulin concentration in the portal system able to inhibit hepatic glucose production, thus preventing fasting hyperglycemia. This observation has prompted the development of dedicated pumps for intraperitoneal insulin delivery which provide a more physiological way to optimize glycemic control and prevent peripheral hyperinsulinemia. Inpatient trials demonstrated that intraperitoneal insulin delivery can improve glycemic control and spare meal-announcement, due to the fast insulin delivery route represented by the peritoneum. This calls for novel control algorithms able to account for the specificities of intraperitoneal insulin kinetics. Recently, we described a 2-compartment model of intraperitoneal insulin kinetics, thus proving that the peritoneal space acts as a virtual compartment and intraperitoneal insulin delivery is virtually intraportal (intrahepatic) delivery, thus mimicking the physiology of insulin secretion. The FDA-accepted type 1 diabetes simulator for subcutaneous insulin delivery and sensing has been updated for intraperitoneal insulin delivery and sensing. In this paper we designed and validated, in silico, a proportional integrative derivative controller to guide intraperitoneal insulin delivery in a fully closed-loop mode not requiring meal announcement.

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