Proceedings of the 2005 IEEE

Engineering in Medicine and Biology 27th Annual Conference

Shanghai, China, September 1-4, 2005

GLUCOSIM: Educational Software for Virtual

Experiments with Patients with Type 1 Diabetes
Baris U. Agar, Meriyan Eren, and Ali Cinar
Department of Chemical and Environmental Engineering
Illinois Institute of Technology
Chicago, IL 60616 USA cinar@iit.edu

Abstract-GLUCOSIM is an educational software of various types of insulin currently available in the market.
package that simulates blood glucose and insulin The body has been divided into several physiologic
dynamics in healthy individuals and patients with type 1 compartments
diabetes. It is being used to assist biomedical and
chemical engineering students in visualizing the dynamic
variations in blood glucose concentration in response to
external variations such as food consumption and insulin
administration. A nutritional database has been
integrated to GLUCOSIM to provide meal inputs to the
simulation. The simulator has been improved by the
modification of mathematical models, and it has been
adapted to include currently available commercial
insulin brands.

I. INTRODUCTION

Type 1 or insulin-dependent diabetes mellitus (IDDM) is

a disease characterized by insufficient secretion of insulin
from E-cells of pancreas, which results in elevated blood
glucose levels. Modeling glucose-insulin interaction in
human body requires an understanding of the physiological
and metabolic processes that influence the variations
observed over time in blood glucose concentration. A
software package, GLUCOSIM has been developed to
simulate blood glucose and insulin dynamics in healthy
individuals and patients with type 1 diabetes for educational
purposes. GLUCOSIM is being used to assist biomedical Fig. 1. Pharmacokinetic diagram of glucose
and chemical engineering students in visualizing the
dynamic variations in blood glucose and insulin
concentrations in response to external perturbations such as (tissues/organs) as illustrated in Fig. 1, and a mathematical
food consumption and insulin administration. It also model is developed by writing mass balance equations
provides an environment for students to perform virtual around each compartment for glucose and insulin. Mass
experiments with food choices, insulin injections and insulin balance for glucose around a specific tissue/organ can be
infusion by automated pumps. Virtual experiments become formulated as:
useful especially when the experiments are either too
expensive or too dangerous to carry out in real life. dGout 1
(Qin , g Gin  Qout , g Gout (1)
dt Vg
II. MODEL
 rproduction  rutilization )
Several compartmental models have been developed to
describe the dynamics of insulin and glucose levels in blood
where V, Q, and G represent the effective volume, effective
[1, 2]. GLUCOSIM utilizes the compartmental model
flow rate and blood glucose concentration respectively,
developed by Puckett [1] as a starting point. Equations have
subscripts “in” and “out” indicate inflow and outflow and
been added and model parameters have been modified to
subscript g indicates glucose. The rate of utilization and/or
simulate healthy individuals (insulin secretion) and effects
production of glucose within the compartment is denoted by

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r. The mathematical model is currently being modified to
incorporate more detailed descriptions of utilization and
production rates of glucose and insulin [2].
The rate of change of glucose concentration in circulating
blood (B) can be expressed as:
using multiple daily insulin injections. Fig. 2 shows the GUI
of the MATLAB version of GLUCOSIM. Here, the user has
the flexibility in assigning different values to the input
variables such as:

dG B 1
[Q H (G B  G H )  Q K (G K  G B ) (2)
dt VB
 Q NS (G N S  G B )  Q PR (G PR  G B )
 Q L G L  (Q HA  Q PN  QGT )G B ].

It is assumed that flow through each compartment is

constant (Qin,g = Qout,g = Qg.), and the subscripts “in” and
“out” for G in (1) are replaced by the symbols of the
previous and succeeding compartments.
A similar pharmacokinetic diagram is utilized to
formulate the mass balance equations for insulin. A detailed
mathematical model is constructed based on mass balances
for the coupled glucose and insulin models, and a set of
simultaneous ordinary differential equations is obtained. A
simplified mathematical model is also derived by assuming
quasi-steady state in each compartment and this results in
two differential equations representing glucose and insulin
concentrations in blood.
Two different submodels for pancreatic insulin release [3,
4] have been integrated to the detailed mathematical model
to simulate glucose-insulin dynamics in a healthy
individual. In addition, a model modification for patients
with type 1 diabetes performing moderate exercise is
incorporated.
III. SIMULATOR
GLUCOSIM is a software for the simulation of plasma
insulin and glucose dynamics in healthy individuals and
patients with type 1 diabetes. The software is available in
several platforms. The mathematical model and a graphical
user interface (GUI) were initially developed in MATLAB
platform [6]. A web-based version of GLUCOSIM is
available at http://216.47.139.198/glucosim, and a stand
alone version has been developed for Windows-based PCs.
GLUCOSIM provides the users with three options to
perform virtual experiments: “Oral Glucose Tolerance Test”
(OGTT), “Healthy Person”, and “Patient with Type 1
Diabetes”. In the patient mode, the user can select between
insulin injections (open-loop control) and automatic
feedback control pumps (closed-loop control) as means of
insulin administration. In addition, a nutritional database to
determine the carbohydrate content of a meal is embedded
in the software.
A. Insulin Injection Therapy
Multiple daily insulin injections is one of the
conventional therapy methods for type 1 diabetes.
GLUCOSIM can simulate a typical type 1 diabetic person
Fig. 2. Simulation window
1. Carbohydrate content of the meal: A nutritional
database is provided to determine the carbohydrate
content of a specific meal.
2. Time of meal and insulin injection: The user can enter
any value for the time of a meal or an insulin injection
within the duration of simulation.
3. Insulin type and dose: The simulator has recently been
modified to include various insulin types currently
available in the market.
4. Body weight
5. Duration of exercise: The exercise option, which is
designed for moderate exercise is currently available
for type 1 diabetic patients.
6. Duration of simulation
The inputs listed above are relevant for investigating the
effects of body weight, carbohydrate intake, insulin dosage,
timing of meal and insulin injections, and duration of
exercise on glucose and insulin dynamics in patients with
type 1 diabetes.
The output of the simulation displays the time course of
several variables of the system such as: glucose and insulin
concentrations in blood, liver glucose production rate, total
glucose uptake etc.
B. Insulin Administration with Feedback Controlled Pumps
The use of insulin infusion pumps is becoming an
appealing therapy method for type 1 diabetes. The current

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commercial use of the pumps is limited to external types
where insulin infusion is regulated by the patient.
Development of an implantable insulin pump and a suitable
control algorithm coupled with a glucose sensor that can
monitor blood glucose levels at frequent intervals is an
active research area in this field and is likely to yield the
artificial pancreas solution for type 1 diabetes.
GLUCOSIM enables the user to experiment not only with
multiple insulin injections but also with futuristic automatic
control of insulin pumps. An important component of this
system is the controller algorithm that regulates the pump
operation based on continuous blood glucose measurements.
The control algorithms employed by GLUCOSIM are
proportional-integral-derivative (PID), internal model
control (IMC) and model predictive control (MPC). The
user has the ability to devise several control strategies by
varying controller parameters or restructuring the controllers
by modifying control equations that relate the difference
between glucose measurements and desired values and the
insulin flow rate from the pump. Fig. 3 shows the variations
Fig. 3. Variations in blood glucose concentration in response
to insulin infusion regulated by feedback-controlled
pumps for PID, IMC and MPC control systems
in blood glucose concentration over time in response to
insulin infusion regulated by feedback-controlled pumps for
PID, IMC and MPC control systems. The dotted (red) line
illustrates the injection rate and glucose concentration
response using a PID controller, the dashed (green) line
shows the effect of the IMC, and the dash-dotted (blue) line
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the MPC. The MPC provides the best controlled response
with high levels of insulin release when the glucose
concentration is increasing rapidly, followed by small
adjustment in the infusion rate as the glucose concentration
stays inside the desired range.In addition, the user can
experiment with two different insulin administration routes:
intraperitoneal and subcutaneous infusions. As expected, the
intraperitoneal route gives better results because of lower
time delay in insulin absorption to the bloodstream.
C. Nutritional Database
One of the inputs to the simulator is the carbohydrate
content of a meal, which may not be readily available for
the user. For this purpose, a nutritional database with a user
friendly GUI is provided on the web incorporated with
GLUCOSIM. It provides a smart spreadsheet that
determines the carbohydrate content of a specific meal and
assigns it as an input to GLUCOSIM. The user can enter the
type of the meal (breakfast, lunch, snack or dinner), the
meal time, and can select any food item from the food
database. A food table is generated for each meal and the
selected foods are added automatically to the table. The
table shows the nutritional content (e.g. carbohydrate, fat,
cholesterol content) of individual food items as well as the
values for the whole meal (Fig.4). After creating the food
table, the user has an option to switch to GLUCOSIM by
choosing one of the simulator modes. The program is
capable of transferring carbohydrate content values from
food tables to GLUCOSIM where they are used as inputs to
the simulation. This way, the user can run GLUCOSIM and
the nutritional database together to inspect the effect of
different combination of foods on glycemic control. The
user can also create an account on the server where he/she
can store various meals for later use.
IV. EDUCATIONAL ACTIVITIES
GLUCOSIM can be used to investigate glucose-insulin
dynamics in human body for educational purposes. It has
been tested by biomedical and chemical engineering
students in various course projects. As an educational tool,
GLUCOSIM provides a virtual experimental environment
for students to reason the combined or isolated effects of
diet, insulin and exercise on blood glucose levels. In these
projects the main objective of the students was to maintain
the glucose level within the normoglycemic range (80-120
mg/dl) by balancing the food intake, insulin dosage,
exercise and timing. Students were asked to respond to
changes in one of these elements by deciding on necessary
adjustments on the others. In addition to the multiple daily
insulin injections, the simulator provides virtual
environment for closed-loop control of plasma glucose
concentration of patients with type 1 diabetes, where
students can tune the controllers by modifying the controller
parameters and can examine the effect of different insulin
infusion routes. This type of studies can lead to the
improvement of their reasoning skills.
 Fig. 4 Food table generated by the nutritional database
GLUCOSIM can also be adapted for use by health-care
professionals to train their patients with diabetes. Using the
simulator, the patients can explore how the adjustment of
diet, insulin dose and timing can affect their daily insulin
regimen. However, the simulator does not take into account
intra- and inter-personal variations and it should not be used
for making medical decisions. GLUCOSIM should only be
used for educational purposes. .
V. CONCLUSIONS
As an educational software package GLUCOSIM has
been very useful for conducting virtual experiments to
simulate blood glucose and insulin dynamics in healthy
individuals and patients with type 1 diabetes. It is being
used to assist undergraduate and graduate biomedical and
chemical engineering students in visualizing dynamic
variations in blood glucose concentration in response to
external variations such as food consumption and testing the
performance of different control algorithms for automated
pumps for insulin infusion.
ACKNOWLEDGMENT
The financial support provided by NSF (EEC-0080527) is
gratefully acknowledged.
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REFERENCES
[1] W. R. Puckett, Dynamic Modeling of Diabetes Mellitus, Ph.D.
Thesis, University of Wisconsin-Madison, Department of
Chemical Engineering, 1992.
[2] J. T. Sorensen, A Physiologic Model of Glucose Metabolism in
Man and Its Use to Design and Assess Improved Insulin
Therapies for Diabetes, Ph.D. Thesis, Massachusetts Institute of
Technology, Department of Chemical Engineering, 1985.
[3] M. Nomura, M. Shichiri, R. Kawamori, Y. Yamasaki, N.
Iwama, and H. Abe, A Mathematical Insulin-Secretion Model
and Its Validation in Isolated Rat Pancreatic Islets Perfusion,
Computers and Biomedical Research, vol. 17, pp. 570–579,
1984.
[4] E. R. Carson and D. G. Cramp, A Systems Model of Blood
Glucose Control, International Journal of Bio-Medical
Computing, vol. 7, pp. 21–34, 1976.
[5] M. Berger, P. Berchtold, H. J. Cuppers, H. Drost, H. K. Kley,
W. A. Muller, W. Wiegelmann, H. Zimmermann-Telschow, F.
A. Gries, H. L. Kruskemper, and H. Zimmermann, Metabolic
and Hormonal Effects of Muscular Exercise in Juvenile Type
Diabetics, Diabetologia, vol. 13, pp. 355–365, 1977.
[6] F.C. Erzen, Studies on Modelling Glucose Insulin Interaction in
Human Body and Development of a Simulation Package, M.S.
Thesis, Illinois Institute of Technology, Chemical and
Environmental Engineering Department, 2000.