Taking the next step in diabetes treatment
Type-1 diabetes is a chronic, incurable condition which still requires careful management and regular injections of insulin. Researchers in the FORGETDIABETES project are working to develop a fully implantable bionic invisible pancreas, which will relieve the burden associated with managing type-1 diabetes, as Professor Claudio Cobelli explains.
An autoimmune condition which leaves the pancreas unable to secrete insulin, type-1 diabetes affects millions of people across the world, and the number is projected to rise further over the coming decades. Managing the disease is quite an onerous task, as patients typically need to monitor their own carbohydrate consumption and inject themselves with insulin from an exogenous source throughout the day. “Managing the condition can impose a heavy burden on patients,” acknowledges Claudio Cobelli, Professor of Bioengineering at the University of Padova in Italy. The situation has improved over the recent past, with technological progress helping to relieve this burden on patients and improve their quality of life. “One important development has been the ability to continuously monitor glucose
The device is implanted in the jejeunum, and includes the magnetic system to attract the ingestible capsule and the system to transfer the insulin from (i) the capsule to the reservoir, and from (ii) the reservoir to the body. Electronic components and sensors allow the device to run automaticly, and communicate with the patient.
concentration. This has been a big step forward,” outlines Professor Cobelli. “A second revolution has been in the ability to inject insulin subcutaneously using various technologies, such as insulin pens.”
by a pump. While hybrid closed loop systems are a major advance in the field, Professor Cobelli says they still have some limitations. “Subcutaneous insulin infusion is very practical, but it isn’t entirely
“I’ve been working to develop an intraperitoneal control algorithm, which involves looking at how the glucose signal can be used to predict the amount of insulin to be infused. The control algorithm is tailored to the patient, it’s an adaptive control algorithm.”
Hybrid closed loop systems
A further step forward has been in the development of so-called hybrid closed loop systems, in which a sensor monitors an individual’s glucose levels, then an algorithm calculates the amount of insulin that should be subcutaneously injected
optimal, as insulin takes time to get into the blood. So people still have to be careful with meal planning and exercise,” he explains. As Principal Investigator of the EU-backed FORGETDIABETES project, Professor Cobelli is part of a team working to develop a bionic invisible
The ingestible capsule acts as insulincarrier, and travels passively along the GI tract up to the implanted device. The capsule is made by soft biocompatible material embedding two metalling rings to facilitate the docking.
pancreas (BIP) designed to address these issues and deliver insulin into patients more effectively. “There are three main components of this artificial pancreas, or hybrid closed loop system. These are the glucose sensor, an algorithm which predicts the amount of insulin needed to maintain blood glucose in the target range, and the actual pump,” he says. The project brings together several partners from across Europe to develop these components, part of a device designed to deliver insulin into the body via an intraperitoneal route. This approach avoids some of the issues associated with subcutaneous insulin infusion, as it closely resembles the normal physiological route, giving people with type-1 diabetes a greater degree of freedom in their daily lives. “It’s like a normal pancreas – insulin
goes in very quickly, and then it also goes out very quickly. The insulin gets to where it needs to go faster,” says Professor Cobelli. The insulin itself comes from a reservoir within the artificial pancreas, which is replenished by ingesting an insulin pill on a weekly basis, a novel aspect of the system developed in the project. “The patient simply ingests a pill of insulin, a smart capsule, which helps to diminish the psycho-social burden of the condition,” continues Professor Cobelli. “This strategy was recognised as a highly novel way of refilling the insulin reservoir by the EUs innovation radar platform.”
A second highly innovative dimension of the project’s work is the development of the control algorithm, which is designed to ensure that a patient with type-1 diabetes receives the appropriate amount of insulin.
Great care needs to be taken here, as insulin is a very potent hormone. “If too little insulin is injected, then glucose levels will go very high (hyperglycaemia) and if too much is injected then glucose levels will go down to below the target range (hypoglycaemia). It’s a classical control problem,” outlines Professor Cobelli. The general consensus is that glucose concentration in the blood should be somewhere between 70-140 mg/ dl (milligrams per 100 millilitres) during the night and 70-180 during the day, with Professor Cobelli working to help keep patients within this range. “I’ve been working to develop an intraperitoneal control algorithm, which involves looking at how the glucose signal can be used to predict the amount of insulin to be infused,” he explains. “The control algorithm is tailored to the patient, it’s an adaptive control algorithm.”
FORGETDIABETES
FORGETDIABETES proposes radically new approach to diabetes treatment
Project Objectives
FORGETDIABETES proposes a radically new therapeutic paradigm resulting from the multidisciplinary combination of innovative technologies (algorithm, miniaturized hardware, smart sensors, experimental surgery). The resulting paradigm has the potential to revolutionize diabetes treatment and to stimulate the emergence of an EU innovation ecosystem.
Project Funding
This project has received funding from European Union’s Horizon 2020 research and innovation programme under grant agreement No 951933.
Project Partners
• University of Padova (UNIPD), Coordinator : Claudio Cobelli
• Scuola superiore di studi universitari e di perfezionamento Sant’Anna (SSSA), PI : Leonardo Ricotti
• Pfützner Science & Health Institute GMBH (PSHI), PI : Andreas Pfützner
• Centre Hospitalier Universitaire de Montpellier (CHUM), PI : Prof. Eric Renard
• Forschungsinstitut der Diabetes-Akademie Bad Mergentheim (FIDAM), PI : Norbert Hermanns
• Lifecare AS, PI : Joacim Holter
• WAVECOMM Srl, PI : Alessio Cucini
https://forgetdiabetes.eu/partners/
Contact Details
Project Coordinator, Claudio Cobelli
Emeritus Professor of Biomedical Engineering IEEE Fellow, BMES Fellow
Department of Woman and Child’s Health University of Padova
Via N. Giustiniani, 3 35128 Padova
Italy
T: +39-335-6055945
E: cobelli@dei.unipd.it W: https://forgetdiabetes.eu/
Claudio Cobelli is Emeritus Professor of Bioengineering at the University of Padova. His research is focused on modelling diabetes and developing new technology to monitor and treat the condition. He received the Diabetes Technology Artificial Pancreas Research Award in 2010 and is a fellow of both the IEEE and BMES.
Glucose concentration
The international consensus around glucose concentration in the blood has formed on the basis of metrics from subcutaneous insulin injection, but Professor Cobelli hopes that it will be possible to narrow the range with intraperitoneal injection, as this approach more closely reflects normal physiology. When we eat our glucose level rapidly increases, as the pancreas secretes insulin very quickly, and Professor Cobelli says the bionic invisible pancreas is designed to work in a similar way. “Intraperitoneal injection will hopefully mimic the normal situation. The pancreas is a very fast-acting organ,” he says. The next step will be to test the system, and plans are in place to assess its overall effectiveness in the final year of the project. “We will test the overall system in pigs that have been rendered diabetic. The pump and the sensor will be implanted and the control algorithm will be embedded,” continues Professor Cobelli. “If the results are convincing then
we hope to continue our research in this area, and we are considering the possibility of a follow-up project.”
This would give researchers the opportunity to refine the device further and bring it closer to clinical application in human patients with type-1 diabetes, which is the ultimate long-term goal. A fully implantable, automated device to deliver insulin would bring significant benefits to patients with type-1 diabetes, releasing them from many of the chores involved in managing the condition, and giving them more freedom to pursue their own interests. “With intraperitoneal delivery of insulin, you don’t have to count the carbohydrates in a meal, which is a procedure that is very difficult to get right. Insulin is delivered very rapidly with the device that we are developing, and it quickly gets to where it needs to go. The target range is narrower, and people are able to control their exercise,” says Professor Cobelli.