Double Intraperitoneal Artificial Pancreas

An easier life with diabetes.

APT illustration (photo: Geir Mogen)

The balance between sugar and insulin is a perpetual challenge in diabetes. It quickly becomes too much or too little. An artificial pancreas will ensure proper blood glucose levels around the clock.

Insulin from the pancreas ensures that your body always has the right amount of glucose (sugar) in the blood. Patients with type 1 diabetes lack this ability to regulate their sugar levels and are dependent on insulin injections many times a day.

The first artificial pancreas that is about to come on the market, has limited effect. It consists of a sensor under the skin that measures sugar level, and a pump outside the body that infuses insulin under the skin. However, such a device is not able to compensate for rapid changes in blood sugar, such as after a meal or strenuous exercise, leaving the patient with either too low or high glucose level.

Scientists in Trondheim work on a completely new way to control glucose levels. They will measure the glucose level inside the abdominal cavity and deliver insulin to the same place. The insulin pump and insulin are placed in a small device on the outside. From this device, an optical fibre for glucose sensing and a thin tube for insulin delivery goes through a small port in the abdominal wall. The port will have a connection that allows for removal of the device whenever needed, for example if the patient wants to go swimming.

The goal is to create a device that mimics the way a healthy body controls blood sugar level, so that the patient does not need to think about diabetes even when he or she is eating or exercising.

This ambitious project involves researchers in medicine, cybernetics, biosensor technology, electronics, product development and materials technology, as well as industry.

The project is led by the research group Artificial Pancreas Trondheim (APT) at NTNU, with St. Olav's Hospital as a research partner and Prediktor Medical AS as an industrial partner.

Project information

  • Category:
    Health
  • Duration:
    2016 - 2020
  • Funding:
    24,7 mill. kr
  • Institution:
    NTNU

Project lead

Sven Magnus Carlsen

E-mail: sven.carlsen@ntnu.no
Phone: 91769528

Profil

Partners

Artificial Pancreas Trondheim (APT), St. Olavs Hospital, Prediktor Medical AS

External resources
  • More about the project
  • Activity
  • Publications
  • Participants

Mimics the body's pancreas

In the project Double Intraperitoneal Artificial Pancreas, the researchers will develop a robust artificial pancreas with fully automatic control of insulin delivery for patients with diabetes type 1. It will give them a better and longer life.

In 1922, insulin was administered to humans for the first time. It stands as one of the great breakthroughs in the history of medicine. Patients with type 1 diabetes who had previously faced a certain death, could now live a long life, but not without complications. Today, these patients still have 10 years’ shorter life expectancy than healthy persons.

One reason for this increased mortality is the difficulty to control the level of glucose (sugar) in patients with type 1 diabetes using current methods. In a healthy body the pancreas produces extra insulin as soon as blood sugar levels begin to rise. In patients with type 1 diabetes, the beta cells that produce insulin are destroyed by autoimmune disease.

Without cells to produce insulin, these patients are dependent on external insulin supply. This can be achieved by injecting insulin into the subcutaneous tissue by a syringe or an insulin pump. Yet, it is very difficult to accurately control the glucose levels in the blood by this manner, and the patient may become hypo- or hyperglycaemic, which in the long-term is harmful to the body.

It has long been a dream to create an artificial pancreas, but no such device is currently able to work fully automatically. Now researchers in Trondheim aim at developing technology to control the supply of insulin automatically around the clock.

Current methods are not accurate enough

The artificial pancreas which today is about to come on the market, consists of a glucose sensor in a needle inserted under the skin, and an insulin pump that infuses insulin under the skin.

This technology will never be accurate enough. Firstly, there is a time lag between when a glucose change occurs in blood until the detection of said change. The delay may be 8 to 20 minutes. Secondly, it takes about 45 minutes from the insulin is pumped under the skin until its level in the blood reaches the top. However, full effect on glucose metabolism is not reached until one and a half to two hours after insulin was delivered.

Another disadvantage with the current approach is that the sensor must be replaced after a few days, and that it must be calibrated a few times a day by the patient using small blood samples.

The researchers in Trondheim will develop technology that closer mimics glucose metabolism in healthy subjects. They place both glucose sensors and insulin delivery inside the abdominal cavity; the fluid-filled space between the intestines. Measurements show that the glucose level is more in line with blood glucose levels. The time delay from the change happens to detection by the glucose sensor, thus becomes small.

More importantly for the response time is that insulin is absorbed much faster in the abdomen than in the skin, and that very much insulin enters the portal vein and then goes directly to the liver. According to preliminary simulations performed by these researchers, this method makes it possible to normalise the level of blood glucose in type 1 diabetes patients.

A small hole in the abdominal wall

An important part of the project is to construct the port to be placed in the abdominal wall. This port must be small, and the goal is that the outside diameter shall not exceed 1 cm. The optical fibre of the glucose sensor and the tubing for administration of insulin must be correspondingly small with a diameter below 4-5 mm.

The port will have a quick release so that the patient can disconnect the equipment when swimming or doing other activities where an insulin pump is a hindrance.

Another important part of the project is to develop technology for continuous measurement of glucose in the abdominal cavity. Here the industrial partner Prediktor Medical in Fredrikstad has an important role.

A third important part is to figure out how the insulin pump must be programmed to automatically give the correct dose of insulin, after the patient eats and glucose levels rise rapidly in the blood. Researchers will find data on the relationship between glucose readings and how supplied insulin in the abdomen affects glucose levels in the blood.

Interdisciplinary

The project brings together researchers from NTNU and St. Olav's Hospital within the disciplines of cybernetics, mathematical modelling, biosensor technology, biotechnology, biochemistry, optical spectroscopy, veterinary medicine and the medical specialties of endocrinology, anaesthesia, intensive care medicine and pharmacology.

Engineers may think completely differently than physicians and attack the issues in a more systematic way. However, it is not always that the doctors realise what the engineers are talking about and vice versa. The project is designed in such a way that researchers from the different disciplines meet each other with an open mind.

Professors, doctoral students and postdocs have meetings every fortnight where there is discussion at the intersection of medicine and technology. Industry partner Prediktor Medical joins the meetings through Skype.

Three PhD students, two postdocs, two scientists and an engineer are working on the project, in addition to the permanent staff at NTNU.

Socially responsible research and innovation

Two of the researchers in the project have diabetes themselves. They have a good understanding of how the treatment of diabetes is at present.


The project will follow national regulations for research on animals and humans. All experiments on animals are approved by the Mattilsynet (the Norwegian animal research authority). All human studies are reviewed by the regional ethics committee before they can be implemented.

Innovation

If researchers succeed in this project, it will be very important for the treatment of patients with diabetes type 1. Around 26,000 people in Norway have this disease. Globally, there are millions. The market for the new solution is large.

NTNU and St. Olav's Hospital have therefore secured the intellectual property rights of the new technologies being developed, but they will not commercialize innovations themselves. This may be done by industrial partners at the forefront of medical technology, such as Prediktor Medical. The project management of Artificial Pancreas Trondheim (APT) has consciously chosen to work with a Norwegian company rather than major international partners in order to keep the rights and commercialisation in Norway.

Activity

Publications


All results in the CRIStin-database

Participants

  • Sven Magnus Carlsen

    Sven Magnus Carlsen

    Professor in clinical research (NTNU) + Consultant in endocrinology, Dept. of Cancer Research and Molecular Medicine (NTNU), Unit for Clinical Research (NTNU), Dept. of Endocrinology (St. Olavs Hospital)

    Head of the Artificial Pancreas Trondheim (APT) research group and the DLN projects "Double Intraperitoneal Artificial Pancreas" (DIAP) and "Listening to the patients". Supervisor for several PhD and master students in the medical part of APT.

    Profile

  • Reinold Ellingsen

    Reinold Ellingsen

    Senior Advisor, Dept. of Electronic Systems

    15 years experience in research and research management (SINTEF), founder of and 12 years as CEO of Invivosense AS/ASA, 4 years as general manager and board member of Invivosense Norway Ltd. Co-founder and board member of GlucoSet AS, a Trondheim based private company established in 2011 on the basis of a patented fiber optic intravascular glucose sensor, previously the Invivosense technology platform. Member of APT's steering group. Sharing responsibility with APT members on sensor technology and development, including IP. Co-supervisor of PhD and post.doc within optical sensor technology.

    Profile

  • Øyvind Stavdahl

    Øyvind Stavdahl

    Professor, Dept. of Engineering Cybernetics

    Six years experience in contract research, innovation and research management from SINTEF, co-founder and former general manager of a startup company, co-founder and former head of the Human Motor Control (HMC) research network in Trondheim. Stavdahl has a solid record of participation in transdisciplinary research, mainly in the medical-technical area. Member of APT's steering group with main responsibility for modelling and control engineering activities.

    Profile

  • Anders Lyngvi Fougner

    Anders Lyngvi Fougner

    Associate Professor, Dept. of Engineering Cybernetics

    MSc and PhD in Engineering Cybernetics, with specialization in medical cybernetics, myoelectric prosthesis control systems. Previously employed as a postdoc in Artificial Pancreas Trondheim during 2014–2017 with focus on modelling and system identification. Dr Fougner is also coordinator of the APT group.

    Profile

  • Astrid Aksnes

    Astrid Aksnes

    Professor, Dept. of Electronic Systems

    She has twenty-five years of experience from SINTEF and NTNU in research and development of optical sensor technology. Since year 2000 she has been member of an EU Expert panel for evaluation and review of project proposals and reports for the EU framework programmes. Supervisor for PhD students and postdocs doing research on optical spectroscopy (Raman and mid-IR) of peritoneal fluid. Project leader for the DLN project 'Lab-on-a-chip biophotonic sensor platform for diagnostics'.

    Profile

  • Dag Roar Hjelme

    Dag Roar Hjelme

    Professor, Dept. of Electronic Systems

    He has more than 25 years of experience from research and development of optical fiber sensor technology. From 2000 to 2010 he was CTO in OptoMed AS and InvivoSense AS working on in vivo application of optical fiber sensor technology. He was supervisor for Sven Tierney and Nils Kristian Skjærvold during their PhDs on glucose sensor development and in vivo sensor testing. He is also a co-founder of GlucoSet AS. Supervisor for PhD students doing research on optical spectroscopy of peritoneal fluid.

    Profile

  • Petter Aadahl

    Petter Aadahl

    Professor (NTNU), Consultant (St. Olavs Hospital)., Department of Circulation and Medical Imaging (NTNU), Department of Anesthesia and Intensive Care Medicine (St. Olavs Hospital)

    Professor in anestesiology at Department of Circulation and Medical Imaging, NTNU. Consultant and former Research Director at St. Olavs Hospital. Long standing interest in glucose monitoring in intensive care units (ICU). Supervisor for Nils Kristian Skjærvold during his PhD on a new glucose sensor.

    Profile

  • Stig William Omholt

    Stig William Omholt

    Research Director, Research Professor

    Long experience in mathematical modeling, systems biology and experimental biology, and in leading multidisciplinary projects involving the concerted operation of experimental and theoretical elements.

    Profile

  • Harald Aagaard Martens

    Harald Aagaard Martens

    Adjunct professor, Dept. of Engineering Cybernetics

    Harald holds a siv.ing. (M.Sc) in biochemistry and dr.techn. in chemometrics. He has 40 years of experience in multivariate datamodelling, in particular for calibration of multichannel instruments to eliminate unexpected interference problems in e.g. biospectroscopy, for interdisciplinary, statistically valid data analysis linking “hard” and “soft” data, and for metamodelling to facilitate high-dimensional nonlinear dynamic models, in particular of complex human and animal physiology. He has published more than 200 papers and several books on these topics. He is currently affiliated with the Department of Engineering Cybernetics at NTNU. His role in APT is as a consultant/advisor in multivariate data modelling.

    Profile

  • Olav Spigset

    Olav Spigset

    Professor of Clinical Pharmacology (NTNU), Senior Consultant (St. Olavs Hospital), Department of Laboratory Medicine, Children's and Women's Health (NTNU), Department of Clinical Pharmacology (St. Olavs Hospital)

    Senior Consultant, Department of Clinical Pharmacology, St. Olavs Hospital and Professor of Clinical Pharmacology, NTNU. He has extensive research experience in clinical pharmacology with focus on pharmacokinetics, pharmacogenetics and drug safety, and has published more than 250 scientific articles. Among other tasks, he is Editor of a Norwegian textbook in pharmacology, has created a national internet-based drug interaction database (www.interaksjoner.no) and is head of the Editorial board of the Norwegian medicines handbook (Norsk legemiddelhåndbok).

    Profile

  • Nils Kristian Skjærvold

    Nils Kristian Skjærvold

    Postdoc, Dept. of Circulation and Medical Imaging (NTNU), Department of Anesthesia and Intensive Care Medicine (St. Olavs Hospital)

    Since January 2015 he is a postdoctoral research fellow on a topic related to APT (Personalized care of critically-ill patients with time-series analysis of oscillating physiology). Currently funded by Samarbeidsorganet (the Liaison Committee between the Central Norway Regional Health Authority and NTNU).

    Profile

  • Sverre Christian Christiansen

    Sverre Christian Christiansen

    Researcher (50%), consultant in endocrinology (50%), Dept. of Cancer Research and Molecular Medicine (NTNU), Dept. of Endocrinology (St. Olavs Hospital)

    Researcher at Department of Clinical and Molecular Medicine. Has worked with APT since November 2014. Consultant in Endocrinology with a PhD in epidemiology of venous thromboembolism from Leiden University Medical Center, Netherlands.

    Profile

  • Konstanze Kölle

    Konstanze Kölle

    Former PhD candidate with Artificial Pancreas Trondheim, Dept. of Engineering Cybernetics

    Dr Kölle received her MSc degree in Chemical Engineering at RWTH Aachen University and worked for APT as a PhD candidate from May 2014 until September 2018. Her PhD thesis entitled "Towards a Safe Artificial Pancreas: Meal Detection and the Intraperitoneal Route" was publicly defended 7 Dec 2018. The main supervisor was Associate Professor Øyvind Stavdahl and the co-supervisors were Professor Sven M. Carlsen and Associate Professor Anders Fougner. Funded mostly by Samarbeidsorganet (the Liaison Committee between the Central Norway Regional Health Authority and NTNU) and in part by the Research Council of Norway (grant no. 248872). Currently working in SINTEF Energy Research.

    Profile

  • Marte Kierulf  Åm

    Marte Kierulf Åm

    PhD candidate, Dept. of Cancer Research and Molecular Medicine

    Cand.med.vet. from the Norwegian School of Veterinary Science in 2006 (now a part of Norwegian University of Life Sciences). Has worked as a veterinary surgeon, as a researcher at The Norwegian Veterinary Institute and as a veterinarian at the Norwegian Food Safety Authority. She started working as a PhD candidate for APT in January 2016. She is primarily focusing on glucose sensing in the intraperitoneal cavity and is the main responsible for animal trials. Supervised by Sven Magnus Carlsen and Sverre Christiansen.

    Profile

  • Ilze Dirnena-Fusini

    Ilze Dirnena-Fusini

    PhD candidate, Dept. of Cancer Research and Molecular Medicine

    Received her MSc degree in Natural Science at University of Latvia in 2012. She completed her studies at Paul Stradins Health and Social Care College, where she received education in internal medicine and attained the diploma of Biomedical Laboratory Assistant. She started working as a PhD candidate for APT in February 2016. She is primarily focusing on insulin absorption in the intraperitoneal cavity. Funded by Samarbeidsorganet (the Liaison Committee between the Central Norway Regional Health Authority and NTNU). Currently on maternity leave. Supervised by Sverre Christiansen and Sven Magnus Carlsen.

    Profile

  • Patrick Christian Bösch

    Patrick Christian Bösch

    Staff Engineer / Development Engineer, Dept. of Engineering Cybernetics

    BSc in Systems Engineering with a specialization in Biomedical Engineering. He graduated from the Zürich University of Applied Science (ZHAW) in Winterthur, Switzerland in 2015. Prior to that he did an apprenticeship as an electrician in Switzerland. Patrick worked with APT for 8 weeks in summer 2015 during an IAESTE internship. Since February 2016 he works for APT as a Staff engineer in the function of a Development Engineer. He is primarily focused on design and prototyping of novel instrumentation based on optical spectroscopy and other relevant sensing modalities for the measurement of glucose in peritoneal fluid, as well as the associated insulin infusion mechanism and related components and systems.

    Profile

  • Ine Larsen Jernelv

    Ine Larsen Jernelv

    PhD candidate, Dept. of Electronic Systems

    Ine Larsen Jernelv received her MSc degree in Nanotechnology from NTNU in 2015 and started working for APT as a PhD candidate in May 2016. She is investigating optical spectroscopy of peritoneal fluid for glucose sensing, both in vitro and in vivo. Supervised by Astrid Aksnes.

    Profile

  • Karolina B. Milenko

    Karolina B. Milenko

    Postdoc, Dept. of Electronic Systems

    Dr Karolina Milenko, postdoctoral research fellow at Department of Electronic Systems, NTNU. MSc and PhD in Physics, with specialization in optical fiber sensing technologies. Employed as a postdoc in Artificial Pancreas Trondheim since June 2016, she focuses on design and development of novel sensing devices for intraperitoneal glucose levels, based on optical spectroscopy methods.​ Supervised by Astrid Aksnes.

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  • Silje Skeide Fuglerud

    Silje Skeide Fuglerud

    PhD candidate, Dept. of Electronic Systems

    Silje Skeide Fuglerud received her MSc degree in Applied Physics from NTNU in 2016, with a specialization in biophysical applications of optics and microfluidics. She wrote her MSc thesis on “Evanescent light field trapping and transport of micro- and nanocrystals of biological macromolecules on a waveguide for serial crystallography” at Deutsches Elektronen-Synchrotron (DESY) in Hamburg, Germany. Silje is a PhD candidate with APT since 2017 and works with methods for optical spectroscopy and sensor fusion. Funded by Samarbeidsorganet (the Liaison Committee between the Central Norway Regional Health Authority and NTNU). Supervised by Dag Roar Hjelme.

    Profile

  • Odd Martin Staal

    Odd Martin Staal

    Former industrial PhD candidate, Dept. of Engineering Cybernetics

    Odd Martin Staal did an industrial PhD with Prediktor Medical and APT/NTNU from 2015 to 2018. He defended his PhD degree in May 2019 and the title of his work is "Blood glucose dynamics: Identification, smoothing and real time estimation in free-living settings". Supervised by Øyvind Stavdahl, Steinar Sælid, Anders L. Fougner and Sven M. Carlsen. Previous experience included a MSc in Engineering Cybernetics (2006), 2 years experience from the Norwegian Defence Research Establishment and 6.5 years experience from medical device development in Axis-Shield PoC.

    Profile

  • Claudia Lopez Zazueta

    Claudia Lopez Zazueta

    ERCIM postdoctoral research fellow, Dept. of Engineering Cybernetics

    Dr Claudia Lopez Zazueta is an ERCIM postdoctoral research fellow at the Department Engineering Cybernetics. MSc in Physics and Mathematics (University of Granada, Spain), with specialization in Mathematical Methods and Models in Science and Engineering, and MSc in Mathematical Sciences (UNAM, Mexico). PhD in Control, Signal and Image Processing (Inria, France). Employed as a postdoc in Artificial Pancreas Trondheim since February 2019, she focuses on mathematical modeling and system identification. Supervised by Anders Lyngvi Fougner and Øyvind Stavdahl.

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  • Sunilkumar Telagam Setti

    Sunilkumar Telagam Setti

    ERCIM postdoctoral research fellow, Dept. of Engineering Cybernetics

    Dr Telagam Setti Sunilkumar is an ERCIM postdoctoral research fellow at the Department Engineering Cybernetics. He received his Ph.D. in Electrical Engineering from the Indian Institute of Technology Indore. His research areas are digital signal processing and machine learning. He is employed as a postdoc in Artificial Pancreas Trondheim since February 2019. His focus is on meal detection based on sound recordings. Supervised by Anders Lyngvi Fougner and Øyvind Stavdahl.

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  • Hasti Khoshamadi

    Hasti Khoshamadi

    PhD candidate, Dept. of Engineering Cybernetics

    Hasti Khoshamadi is a PhD candidate at Dept. of Engineering Cybernetics and with APT since March 2019. Received her MSc degree in Electrical Engineering (Control) from K. N. Toosi University of Technology, Tehran, Iran, November 2018. Her focus is on mathematical modeling and system identification. Supervised by Anders Lyngvi Fougner and Øyvind Stavdahl.

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  • Ludvig Stangeland Sæle

    Ludvig Stangeland Sæle

    MSc student, Dept. of Engineering Cybernetics

    Ludvig S. Sæle pursues his MSc thesis at Dept. of Engineering Cybernetics during Fall 2019, on a topic related to parametric uncertainty in model-based control. Supervised by Anders Lyngvi Fougner.

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  • Nora Lyngstad Røste

    Nora Lyngstad Røste

    MSc student, Dept. of Engineering Cybernetics

    Nora Lyngstad Røste pursues a term project at Dept. of Engineering Cybernetics during Fall 2019, on a topic related to meal detection. Supervised by Anders Lyngvi Fougner and Sunilkumar Telagam Setti.

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  • Sigurd Heide Rosland

    Sigurd Heide Rosland

    MSc student, Dept. of Engineering Cybernetics

    Sigurd Heide Rosland pursues a term project at Dept. of Engineering Cybernetics during Fall 2019, on sensor and pump interface for closed-loop glucose control experiments. Supervised by Anders Lyngvi Fougner and Øyvind Stavdahl.

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  • Einar Henriksen

    Einar Henriksen

    MSc student, Dept. of Engineering Cybernetics

    Einar Henriksen pursues a term project at Dept. of Engineering Cybernetics during Fall 2019, on a topic related to meal detection. Supervised by Anders Lyngvi Fougner and Sunilkumar Telagam Setti.

  • Mary Ann Lundteigen

    Mary Ann Lundteigen

    Professor, Dept. of Engineering Cybernetics

    Professor Mary Ann Lundteigen, Dept. of Engineering Cybernetics, has her main research interest within functional and failure analysis, functional safety, reliability analysis, safe design principles with main application area with safety-instrumented systems. Has been involved in risk analysis also with Artificial Pancreas Trondheim.

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  • Sebastien Gros

    Sebastien Gros

    Professor, Dept. of Engineering Cybernetics

    Professor Sebastien Gros, Dept. of Engineering Cybernetics, has his main research interest within model predictive control (MPC) and reinforcement learning. He is involved in APT's work on applying MPC/optimization in glucose control.

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  • Terje Rølvåg

    Terje Rølvåg

    Professor, Dept. of Mechanical and Industrial Engineering

    Terje Rølvåg holds a MSc and a PhD within finite element dynamics of elastic mechanisms from NTH. His working experience includes Sintef Production Engineering, Sintef Materials Technology, Fedem Technology AS, ColiCot and TRAC, the latter in combination with an adjunct professorship at Department of Engineering Design and Materials (IPM), NTNU. Since 2003 he has been a full time professor within the Engineering Design group at IPM. Rølvåg has 30 years of experience in Product Development with a focus on Computer Aided Engineering. His role is to develop and optimize AP concepts with respect to design and functionality for experimental and commercial use.

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  • Andrea Holten

    Andrea Holten

    MSc student, Dept. of Engineering Cybernetics

    Andrea Holten pursues a term project at Dept. of Engineering Cybernetics during Fall 2019, on a topic related to meal detection. Supervised by Anders Lyngvi Fougner and Sunilkumar Telagam Setti.

    Profile

  • Chris Arun Muralitharan

    Chris Arun Muralitharan

    MSc student, Dept. of Engineering Cybernetics

    Chris Arun Muralitharan pursues a term project at Dept. of Engineering Cybernetics during Fall 2019, on Kalman filter for sensor fusion in biomedical applications. Supervised by Anders Lyngvi Fougner.