The Artificial Pancreas - Diabetes & Control
Section for Scientific Computing, DTU Compute, Technical University of Denmark
DIACON
The objective of the DIACON group - The Copenhagen Diabetes Control group - is to develop an artificial pancreas for people with type 1 diabetes.
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You can read about the DIACON project in the slides and posters below:
Diabetes and the Artificial Pancreas
The beta cells in the pancreas of people with type 1 diabetes are not able to produce insulin.
Insulin is a hormone that lowers the blood glucose concentration by catalyzing storage of glucose
in the liver as glycogen and by facilitating uptake of glucose in muscles and adipose tissue.
To maintain glucose homeostasis, people with type 1 diabetes must inject insulin. In this project,
we develop technology that automatically injects the right amount of insulin at the right time.
This releases people with type 1 diabetes from the burdensome task of controlling their disease
themselves. Also we expect better control of the blood glucose concentration, such that a number of
complications arising from poor blood glucose control are mitigated.
Conventional Multiple Daily Injections (MDI) Based Insulin Therapy
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The subcutaneous glucose concentration as function of time for several days for one individual
using best practice conventional diabetes therapy. In conventional best practice insulin therapy,
basal long acting insulin is taken once daily to counteract endogeneous glucose production by the liver
and fast acting insulin is taken at meal times to counteract the carbohydrates in the food. As indicated
in the figure, using MDI based insulin therapy it is hard to stay in the target blood glucose range. If
the blood glucose concentration get too low, the individual may go into coma. In severe cases the
consequences may even be fatal. If the blood glucose concentration is high for longer times
cardiovascular, kidney, nerve, and eye diseases may arise. The pictures below illustrate some of
these complications.
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The Pancreas and Glucose Homeostasis
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For people without diabetes, the pancreas releases a number of hormones for glucose homeostasis.
When the blood glucose is high, insulin is released from the beta cells of the pancreas. This
stimulates storage of glucose as glycogen in the liver and uptake of glucose in tissue cells. As a
consequence, the blood glucose concentration decreases. If the blood glucose concentration is low,
glucagon is released from the alpha cells of the pancreas. In the liver, glucagon stimulates conversion
of glycogen to glucose. The end result is that the blood glucose concentration increases. Insulin and
glucagon are the central hormones for glucose homeostasis. However, also amylin plays a role in the
glucose homeostasis.
The Artificial Pancreas (Beta Cell) - Insulin Infusion Pump & CGM
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The Artificial Pancreas - Insulin and Glucagon Infusion Pumps & CGMs
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Publications
PhD Theses
Sabrina Lyngbye Wendt: Modeling Pharmacokinetics and Pharmacodynamics of Glucagon for Simulation of the Glucoregulatory System in Patients with Type 1 Diabetes, 2017
Dimitri Boiroux: Model Predictive Control Algorithms for Pen and Pump Insulin Administration, 2012
MSc Theses
Daniel Liljegren Dinesen: Simulation, Control and Optimization for Diabetes Technology, 2019
André Bötcher Larsen: Simulation, Control and Optimization for Diabetes Technology, 2019
Asbjørn Thode Reenberg: Model Predictive Control of the Glucose Concentration in Man, 2018-2019
Maximilian Felix Appel: Ensemble Based Model Predictive Control for the Artificial Pancreas, 2017
Anders Bøge Paulsen: Modeling and Simulation of the Glucose Dynamics in People with Diabetes, 2016
Tinna Björk Aradottir: Parameter Estimation in Models for Glucose-Insulin Dynamics in People with Type 1 Diabetes, 2014-2015
Caroline Johannsen: Software for Advanced Control in an Artificial Pancreas, 2014-2015
Stefan Høngaard Andersen: Software for in Silico Testing of an Artificial Pancreas, 2013-2014
Christina Hemmingsen: Prediction of Glucose in Type-1 Diabetics, 2009
Charlotte Aagaard Johnsen: Prediction of Glucose in Type-1 Diabetics, 2009
Dimitri Boiroux: Nonlinear Model Predictive Control for the Artificial Pancreas, 2009
Allan Gøttig: Model Predictive Regulation, 2008
Vidar Hrafnkelsson: A Dynamic Model for in vivo Glucose-Insulin Metabolism, 2006-2007
BSc Theses
Ragnar Palsson: High-Performance Computing for Simulation of Glucose Dynamics in People with Diabetes, 2016
Nicolai Schmidt: Filtering for Fault Detection in Continuous Glucose Monitors (CGMs), 2016
Mark Ian Svenningsen: Modular Approach to an Artificial Pancreas Research Platform, 2014-2015
Miriam M.N. Nærum: Model Predictive Control for Insulin Administration in People with Type 1 Diabetes, 2010
Søren Nygaard Pedersen: System Identification for Prediction of Glucose Levels in People with Type 1 Diabetes, 2010
Lasse Bergenholz Hansen: System Identification for Prediction of Glucose Levels in People with Type 1 Diabetes, 2010
Karen Sandø Jensen: Detection of Events using Continuous Glucose Monitors, 2010
Mette Pejtersen: Detection of Events using Continuous Glucose Monitors, 2010
Diego Al Safi: Detection of Events using CGM, 2009
Emil G.S. Munk: Detection of Events using CGM, 2009
Jakob Rich Madsen: Modeling and Simulation of Glucose-Insulin Dynamics, 2009
Mads Andersen: Modeling and Simulation of Glucose-Insulin Dynamics, 2009
Sabrina Lyngbye Wendt: Physiological Model for Gastric Emptying, 2009
Thor S.S. Nielsen: Modeling and Simulation of Glucose-Insulin Dynamics, 2008
Allan Lyngby Lassen: Modeling and Simuation of Glucose-Insulin Dynamics, 2008
Simon Kristiansen: Model Predictive Control for an Artificial Pancreas, 2007
Mathias Sørensen: Model Predictive Control for an Artificial Pancreas, 2007
Esben Friis-Jensen: Modeling and Simulation of Glucose-Insulin Metabolism, 2007
Minor Project Reports
Agnes Martine Nielsen: Simulation and Modelling of Glucose and Insulin Dynamics, 2012
Astrid Enslev Vestergård: Simulation and Modelling of Glucose and Insulin Dynamics, 2012
Søren Føns Vind Nielsen: Simulation and Modelling of Glucose and Insulin Dynamics, 2012
Rasmus Dalgas Rasmussen: Simulering og styring af glukose-insulin dynamik, 2011
Christian Wichmann Moesgaard: Simulering og styring af glukose-insulin dynamik, 2011
Andreas Falkenstrøm Mieritz: Simulering og styring af glukose-insulin dynamik, 2011
Simon Grejs Andersen - Simulering af en bugspytkirtel, 2008
Jakob Schack Vestergaard - Simulering af en bugspytkirtel, 2008
Papers
- An automated meal detector and bolus calculator in combination with closed-loop blood glucose control
Z. Mahmoudi, D. Boiroux, F. Cameron, N.K. Poulsen, B.W. Bequette, J.B. Jørgensen
- Design of Switched Model Predictive Control Algorithms for a Dual-Hormone Artificial Pancreas
D. Boiroux, V. Batora, Z. Mahmoudi, J.B. Jørgensen
- Relationship between optimum mini-doses of glucagon and insulin levels when treating mild hypoglycemia in patients with type 1 diabetes - A simulation study
A. Ranjan, S.L. Wendt, S. Schmidt, S. Madsbad, J.J. Holst, H. Madsen, J.B. Jørgensen, K. Nørgaard
- Evaluation of model designs for subcutaneous infusion of insulin aspart
E.J. Mansell, S. Schmidt, P.D. Docherty, K. Nørgaard, J.B. Jørgensen, H. Madsen
- Overnight glucose control in people with type 1 diabetes
D. Boiroux, A.K. Duun-Henriksen, S. Schmidt, K. Nørgaard, S. Madsbad, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Fault and Meal Detection by Redundant Continuous Glucose Monitors and the Unscented Kalman Filter
Z. Mahmoudi, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Adaptive Unscented Kalman Filter using Maximum Likelihood Estimation
Z. Mahmoudi, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- A Riccati-Based Interior Point Method for Efficient Model Predictive Control of SISO Systems
M. Hagdrup, R. Johansson, J.B. Jørgensen
- A Model for Simulating Fasting Glucose in Type 2 Diabetes and the Effect of Adherence to Treatment
T.B. Aradottir, D. Boiroux, H. Bengtsson, J. Kildegaard, B. Van Orden, J.B. Jørgensen
- Cross-Validation of a Glucose-Insulin-Glucagon Pharmacodynamics Models for Simulation using Data from Patients with Type 1 Diabetes
S.L. Wendt, R. Ajenthen, J.K. Møller, S. Schmidt, C. Knudsen, J.J. Holst, S. Madsbad, H. Madsen, K. Nørgaard, J.B. Jørgensen
- C Code Generation Applied to Nonlinear Model Predictive Control for an Artificial Pancreas
D. Boiroux, J.B. Jørgensen
- An adaptive nonlinear basal-bolus calculator for people with type 1 diabetes
D. Boiroux, T.B. Aradottir, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Model design and selection for continuous subcutaneous infusion of insulin aspart using clinical data
E. Mansell, P. Docherty, S. Schmidt, K. Nørgaard, J.B. Jørgensen, H. Madsen
- Modelling of Glucose-Insulin-Glucagon Pharmacodynamics in Man
S.L. Wendt, J.K. Møller, A. Haidar, C.B. Knudsen, H. Madsen, J.B. Jørgensen
- PK/PD modeling of glucose-insulin-glucagon dynamics in healthy dogs after a subcutaneous bolus administration of native glucagon or a novel glucagon analogue
S.L. Wendt, J.K. Møller, C.B. Knudsen, H. Madsen, A. Haidar, J.B. Jørgensen
- On Discretization, Regularization and Tuning in Linear Model Predictive Control
M. Hagdrup, H. Madsen, N.K. Poulsen, J.B. Jørgensen
- An Efficient Square Root Algorithm for the Computation of Maximum Likelihood Sensitivity of Continuous-Discrete Systems
D. Boiroux, R. Juhl, H. Madsen, J.B. Jørgensen
- Comparison of Three Nonlinear Filters for Fault Detection in Continuous Glucose Monitors
Z. Mahmoudi, S.L. Wendt, D. Boiroux, M. Hagdrup, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- On the significance of the noise model for the performance of a linear MPC in closed-loop operation
M. Hagdrup, D. Boiroux, Z. Mahmoudi, H. Madsen, N.K. Poulsen, B. Poulsen, J.B. Jørgensen
- Model Identification using Continuous Glucose Monitoring Data for Type 1 Diabetes
D. Boiroux, M. Hagdrup, Z. Mahmoudi, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Application of the Continuous-Discrete Extended Kalman Filter for Fault Detection in Continuous Glucose Monitors for People with Type 1 Diabetes
Z. Mahmoudi, D. Boiroux, M. Hagdrup, N.K. Poulsen, H. Madsen, K. Nørgaard, J.B. Jørgensen
- An Ensemble Nonlinear Model Predictive Control Algorithm in an Artificial Pancreas for People with Type 1 Diabetes
D. Boiroux, M. Hagdrup, Z. Mahmoudi, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- A Bolus Calculator Based on Continuous-Discrete Unscented Kalman Filtering for Type 1 Diabetics
D. Boiroux, T.B. Aradottir, M. Hagdrup, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Comparison of Prediction Models for a Dual-Hormone Artificial Pancreas
D. Boiroux, V. Batora, M. Hagdrup, M. Tarnik, J. Murgas, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Glucagon Administration Strategies for a Dual-Hormone Artificial Pancreas
V. Batora, D. Boiroux, M. Hagdrup, M. Tarnik, J. Murgas, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Adaptive Control in an Artificial Pancreas for People with Type 1 Diabetes
D. Boiroux, A.K. Duun-Henriksen, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Model Identification using Continuous Glucose Monitoring Data for People with Type 1 Diabetes
D. Boiroux, M. Hagdrup, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Diabetes Self-monitoring Data: Prediction of Glycemia
M. Tarnik, V. Batora, T. Ludwig, I. Ottinger, E. Miklovicova, J. Murgas, J.B. Jørgensen
- Bihormonal Model Predictive Control of Blood Glucose in People with Type 1 Diabetes
V. Batora, M. Tarnik, J. Murgas, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Bihormonal Control of Blood Glucose in People with Type 1 Diabetes
V. Batora, M. Tarnak, J. Murgas, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Assessment of Model Predictive and Adaptive Glucose Control Strategies for People with Type 1 Diabetes
D. Boiroux, A.K. Duun-Henriksen, S. Schmidt, K. Nørgaard, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Predicting plasma glucose from interstitial glucose observations using Bayesian Methods
A.H. Hansen, A.K Duun-Henriksen, R. Juhl, S. Schmidt, K. Nørgaard, J.B. Jørgensen, H. Madsen
- Model-Based Closed-Loop Glucose Control in Type 1 Diabetes - The DiaCon Experience
S. Schmidt, D. Boiroux, A.K. Duun-Henriksen, L. Frøssing, O. Skyggebjerg, J.B. Jørgensen, N.K. Poulsen, H. Madsen, S. Madsbad, K. Nørgaard
- Model Identification Using Stochastic Differential Equation Grey-box Models in Diabetes
A.K. Duun-Henriksen, S. Schmidt, R.M. Røge, J.B. Møller, K. Nørgaard, J.B. Jørgensen, H. Madsen
- Overnight Control of Blood Glucose in People with Type 1 Diabetes
D. Boiroux, A.K. Duun-Henriksen, S. Schmidt, K. Nørgaard, S. Madsbad, O. Skyggebjerg, P.R. Jensen, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Tuning of Controller for Type 1 Diabetes Treatment with Stochastic Differential Equations
A.K. Duun-Henriksen, D. Boiroux, S. Schmidt, O. Skyggebjerg, S. Madsbad, P.R. Jensen, J.B. Jørgensen, N.K. Poulsen, K. Nørgaard, H. Madsen
- Effects of Everyday Life Events on Glucose, Insulin, and Glucagon Dynamics in Continuous Subcutaneous Insulin Infusion - Treated Type 1 Diabetes: Collection of Clinical Data for Glucose Modeling
S. Schmidt, D.A. Finan, A.K. Duun-Henriksen, J.B. Jørgensen, H. Madsen, H. Bengtsson, J.J. Holst, S. Madsbad, K. Nørgaard
- Control of Blood Glucose for People with Type 1 Diabetes: an in Vivo Study
D. Boiroux, S. Schmidt, A.K. Duun-Henriksen, L. Frøssing, K. Nørgaard, S. Madsbad, O. Skyggebjerg, P.R. Jensen, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Strategies for glucose control in people with type 1 diabetes
D. Boiroux, D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
- Insulin Administration for People with Type-1 Diabetes
D. Boiroux, D.A. Finan, N.K. Poulsen, H. Madsen, J.B. Jørgensen
- Implications and Limitations of Ideal Insulin Administration for People with Type 1 Diabetes
D. Boiroux, D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
- Robust model identification applied to type 1 diabetes
D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
- Nonlinear Model Predictive Control for Artificial Beta-Cell
D. Boiroux, D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
- Optimal Insulin Administration for People with Type 1 Diabetes
D. Boiroux, D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
- Meal Estimation in Nonlinear Model Predictive Control for Type 1 Diabetes
D. Boiroux, D.A. Finan, J.B. Jørgensen, N.K. Poulsen, H. Madsen
Links - Research Groups
Artificial Pancreas
The DiaCon Group (DTU / Hvidovre Hospital, H. Madsen, J.B. Jørgensen & K. Nørgaard)
Artificial Pancreas at home (Hans de Vries & Lutz Heinemann)
The Danish Diabetes Academy (Henning Bech-Nielsen, Kurt Højlund, …)