Proceedings of the Second Joint EMBS/BMES Conference
Houston, TX, USA • October 23-26, 2002
TYPE I DIABETES: MODELING, IDENTIFICATION AND NON-LINEAR
MODEL PREDICTIVE CONTROL
G. Schlotthauer, G. A. Nicolini, L. G. Gamero, M. E. Torres
Facultad de Ingeniería, Universidad Nacional de Entre Ríos, Paraná, Argentina.
Abstract-Patients with Diabetic Type I nearly always need a
therapy with insulin. The most desirable treatment would be to
mimic the operation of a normal pancreas. In this work we
model a patient affected with this pathology, identify it with a
neural network, and evaluate a control strategy known as
Nonlinear Model Predictive Control as an approach to
command an insulin pump using the subcutaneous route.
Keywords - Diabetes, modeling, identification, non-linear
control, neural networks.
I. INTRODUCTION
Insulin-Dependent Diabetes Mellitus (IDDM) is a chronic
metabolic disorder, which is characterized by an increased
blood glucose level. When this level is sustained, it causes
several complications, like nephropathies, neuropathies and
retinopathies. This high level is caused by a decreased or
absent pancreatic insulin production. In most of cases,
patients who suffer Diabetes Type I need a therapy with
several insulin injections a day or with an insulin pump.
None of these approaches reach a physiological condition.
Due to this fact, our objective is to substitute the pancreas
function using a pump controlled by the current glucose
level. In order to avoid complications related to continuous
vascular access, we intend to reach this goal using the
subcutaneous (s.c.) route, both to sense glucose levels and to
inject insulin. This approach would be by far superior to the
intravenous route due to its management and safety. The
system we want to control presents nonlinear dynamics. It
also has time delays associated with insulin absorption from
subcutaneous tissue to blood and with the transfer rate
between plasmatic and subcutaneous glucose. Additionally
there are dead times due to the tubing in the monitoring
system.
Model Predictive Control (MPC) is a control strategy that
predicts system outputs based on an appropriate linear model
and calculates future control actions that are necessary to fit
a desired output, by mean of an optimization algorithm [1].
To accomplish this task, this strategy needs a precise model
of the system to be controlled. A linear model can not deal
with this highly non-linear system. In order to overcome this
problem we choose a neural network to model it. This
strategy, based on the MPC idea, is called Non-Linear Model
Predictive Control (NMPC)[1]. In this preliminary paper we
propose a new approach to the model, identification and
control of the subcutaneous insulin administration in IDDM
patient.
II. METHODOLOGY
We can divide our problem in three parts: the diabetic
patient model, its identification using neural networks, and
its control using the NMPC strategy.
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1) Diabetic patient model: This model is composed of
three subsystems. The first one represents subcutaneous
insulin dynamics. The next one takes into account general
metabolism, considering plasmatic, hepatic and pancreatic
concentrations of glucose, insulin and glucagon. Finally, the
last subsystem corresponds to the interactions between
plasmatic and subcutaneous glucose concentrations, and to
the monitoring system. (Fig. 1.)
Fig. 1. Patient Model. It is composed by three subsystems: the first one
models the s.c. insulin absorption into plasma. The second subsystem
models the glucose dynamics and its regulation, and the last one represents
the glucose evolution sensed in the s.c. tissue. The arrows represent inputs
and outputs from these subsystems.
In the first subsystem we use the model proposed in [2]
and modified in [3] for the s.c. insulin absorption into the
blood. However, this model only takes into account a single
injection. To simulate multiple injections we assume injected
volumes Vsc1, Vsc2, ···, Vscn at times t1, t2, ···, tn, we have:
 
di Bm  
=
∫
 m(t − t1 ) dV +
dt V p  ∫ ∫
m(t − t 2 ) dV + L m(t − t n )dV  − K m ,
 (1)
 Vsc1 V sc 2 V scn 
where i is the plasmatic insulin concentration [mU l-1], m is
the s.c. insulin concentration [mU l-1], Bm is the absorption
rate constant [min-1], Vp is the volume of plasma insulin
compartment [l], and Km is the plasma insulin elimination
rate constant for insulin [min-1].
The insulin absorption into plasma is a slow process. In
case of injections applied at a frequency of 1 injection/min,
the evaluation of (1) is strongly slowed. We propose to
obtain an identification with an autorregresive model (AR)
conferring simplicity and a faster computation. We adjusted
an AR model with 500 input/output samples. If v(t) is the
injected volume, we have:
1.220
i (t ) = v (t ) (2)
1 − 0.988q −1
A validation test was performed on the identified AR
model [4]. The mean square error (MSE) evaluated in the
validation was 1.23 10-8. We maintain this model due to its
simplicity and precision.
The model of the plasmatic glucose-insulin system is
based on [5]. The last subsystem is assumed as a first order
linear system with dead time as in [6].
2) Non-Linear Identification with Neural Networks: In
previous works [6] Radial Basis Function Networks (RBF)
have been used instead of Multilayer Perceptrons (MLP).
The RBF network has a theoretical support that favors them
and it offers training times one to three orders of magnitude
faster than the standard back-propagation algorithm used for
the MLP of similar power and generality. However, it should
be kept in mind that these advantages are important in a
mathematical sense and in the training stage. The economy
of the implementation can be considered more critical in an
engineering application. In our specific case, the MLP
separates the space of features with less units than the RBF
network, being more economical. Additionally, we use the
Levenberg-Marquardt algorithm, which is faster than the
classical Back-Propagation algorithm.
3) Non-Linear Model Predictive Control: The MPC and
the NMPC are based on: a) the explicit utilization of a model
to predict the process' output in future time instants
(horizon), b) the calculation of a control sequence
minimizing a target function, and c) a sliding strategy, i.e. at
each time instant the horizon is shifted and the first control
signal of the sequence is applied. It can be used to control a
wide range of processes, including systems with large time
delays, non-minimum phase systems and unstable systems.
Additionally, it have an intrinsic compensation for dead
times and it can compensate measurable perturbations in a
natural way. For these reasons, this method is suitable for
our problem. It is very important to take into account that we
can not inject negative quantities of insulin, so here we have
a strong restriction. Furthermore, the patient who reaches a
hypoglycemia (a low level of glucose in blood) for several
minutes could die.
III. RESULTS
The identification of the patient model was achieved with
a MLP neural network using 12 input units (6 for insulin
injections and 6 for subcutaneous glucose concentration) and
15 hidden units. An acceptable long time prediction was
reached, with a MSE of 10-3 in a 40-steps ahead prediction.
This identification was validated following [4].
With this non-linear model, we can use the NMPC
technique, which decides the future control variable value
over the control horizon minimizing a target function and
predicting the future system's output using the trained MLP.
The chosen function is shown in (3). This is a quadratic
function of the difference between the predicted and desired
output at instant t+j (ej), and penalizes the abrupt changes of
the control variable (∆u) with a factor Γu. Nu is the control
horizon (we use Nu =1 for a faster computation). N1 and N2
are the minimum and maximum prediction horizons. N1 is
fixed as the dead time and N2 is extended as long as possible
in order to obtain a more stable control. Γu value was
adopted by trial and error.
In Fig. 2 can be seen the results from the control in a
diabetic patient model, with basal glycemia of 91.5 [mg/dl]
after the oral intake of 50 g of glucose. The maximum
N2 N u −1
J= ∑ (e Tj e j ) + ∑ (∆u T (t + j)Γu ∆u (t + j ))
j = N1 j =0
(3)
Fig. 2. OGTT response after an intake of 50 g of glucose. a) Glucose
absorption from gut to plasma, in [g/min]. b) Glucose in plasma evolution.
A maximum of 142.58 [mg/dl] and a minimum of 76.01 [mg/dl] are
reached c) Insulin injections, as results of the NMPC.
glucose concentration is 142.58 [mg/dl] after 95 minutes
from the intake, and the minimum is 76.01 [mg/dl], not
reaching the hypoglycemia. The parameters were set as:
N1=11, N2=80, and Γu=0.0015.
IV. DISCUSSION AND CONCLUSION
The NMPC strategy can be used as a method to control
this highly non-linear system, considering the dead time and
the restrictions. It is important to remark that the intake of
glucose is not a normal behavior of a diabetic patient, who is
imposed to strict diets. Thus, in real situations, we can think
that this kind of control would be appropriate. There are
some problems associated with this method that are still not
completely resolved, such as instability depending on the
parameters.
REFERENCES
[1] E. Camacho and C. Bordons, Model Predictive Control.
Springer, 1999.
[2] E. Mosekilde, K. Jensen, C. Binder, S. Pramming, and B.
Thorsteinsson, “Modelling absorption kinetics of
subcutaneous injected soluble insulin,” J. Pharmakokinetic
Biopharm., vol. 17, pp. 67-87, 1989.
[3] P. Wach, Z. Trajanoski, P. Kotanko, and F. Skrabal,
“Numerical approximation of mathematical model for
absorption of subcutaneously injected insulin,” Med. & Biol.
Eng. & Comput., vol. 33, pp. 18-23, 1995.
[4] S.A. Billings and W.S.F. Voon, “Correlation based
model validity tests for non-linear models,” Int. J. Control,
vol. 44, pp. 235-244, 1986.
[5] C. Cobelli, G. Nucci, and S.D. Prato, “A physiological
simulation model of the glucose-insulin system in type I
diabetes,” Comp. in Diab., pp. 11-78, 1998.
[6] Z. Trajanoski and P. Wach, “Neural predictive controller
for insulin delivery using the subcutaneous route,” IEEE
Trans. Biomed. Eng. vol. 45, pp. 1122-1134, 1998.

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