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.

Portable Artifician Pancreas 

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

Conventional Insulin Therapy 

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.

Diabetes Complications 

The Pancreas and Glucose Homeostasis

Pancreas and Hormones 
Glucose Homeostasis 

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

Portable AP Diagram 
Portable AP 

The Artificial Pancreas - Insulin and Glucagon Infusion Pumps & CGMs

Insulin Glucagon AP 

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

Modeling

Links - Companies & Non-Profit Organizations

Pharmaceuticals

Devices

Non-Profit Organization

Various

Links - Journals and Conferences

Journals

Conferences