A Performance Comparison between Standard and

Impulsive ZMPC on Type 1 Diabetic Patients

Juan E. Sereno
Facultad de Minas
Universidad Nacional de Colombia
Medellı́n, Colombia
Email: jeserenom@unal.edu.co
Alejandro H. González
INTEC-Facultad de Ingenierı́a Quı́mica
UNL-CONICET
Santa Fe, Argentina
Email: alejgon@santafe-conicet.gov.ar
Pablo S. Rivadeneira
Facultad de Minas
Universidad Nacional de Colombia
Medellı́n, Colombia
Email: psrivade@unal.edu.co

Abstract—Type 1 diabetes mellitus is a worldwide chronic
and autoimmune disease affecting almost 25 million individual
around the world. Particularly, in Colombia, it has an annual rate
of growth of 3% - 5%. Current research in the treatment of this
illness is aimed at the implementation of the so-called Artificial
Pancreas, a device that allows the regulation of blood glucose
levels automatically. Recently, several model predictive control
strategies has been developed to accomplish that. In this work, a
performance comparison between a standard model predictive
control (MPC) and a novel impulsive zone MPC scheme is
made based on a novel long-term glucose insulin model. The
proposed control strategies ensure the stability under moderate-
to-severe disturbances. A long-term scenario - including meals
- are simulated and tested in 20 virtual patients. The results
appear to be satisfactory as long as every hyperglycemia and
hypoglycemia episodes are suitably controlled. The performance
comparison also shows that the standard MPC is 70% of the
time in the target zone, while the iZMPC is 92.5%.
I. I NTRODUCTION
Type 1 diabetes mellitus (T1DM) is a chronic and au-
toimmune disease that cause progressive destruction of the
pancreatic β-cells. As a consequence, the natural endogenous
production of insulin disappears, thus resulting in a dysfunc-
tional glycemic regulation. In Latin America is estimated that
the prevalence of T1DM will increase by 250% over the next
20 years and its cost in health budget will be three times
higher. The inclusion of insulin pump therapy have had a
good acceptance due to the positive clinical results on diabetes
control (quality of life and costs), but its performance in
Colombia and Latin America is still not very well studied,
especially in outpatient routine [1].
The idea of an artificial pancreas was envisioned more than
50 years ago; it is a device that closes the loop between
the measurements of continuous glucose monitoring system
(CGM) and insulin pump injection/infusion. Nowadays, model
predictive control (MPC) has been the most developed control
strategy for the artificial pancreas [2]–[6]. The standard zone
MPC (ZMPC) is a type of model predictive control algorithm
that computes the optimal future inputs to maintain the pre-
dicted output within a desired zone rather than at a single set-
point [7], [8]. An improved version of ZMPC is the one that
uses intermediary variables - additional variables forced to lie
in the system equilibrium subspace - and permits a significant
enlargement of the controller domain of attraction [9], [10].
This technique was also adapted to impulsive controls systems
(ICS) in [11], and a first attempt to control T1DM patients was
made in [12].
The formulation proposed in [12] takes advantage of two
underlying discrete-time systems (computed at the time in-
stants when the impulses are applied), to produce the so-called
impulsive MPC (iZMPC); a controller that control the plant
by impulses instead of continuous input actions.
In this work, both techniques, the standard ZMPC and the
iZMPC, are tested and compared here throughout 20 virtual
patients (but coming from real life data provided by the
‘Centre Hospitalier de Nantes’, in Nantes-France, and the
‘Clı́nica Integral de Diabetes’ of Medellı́n, Colombia) and
using a new T1DM model detailed in [13]. This model is
based on the functional insulin therapy and has the advantage
of representing the patient realistically, which mainly means
that it has a critically stable equilibrium manifold (instead of
a stable one), and predicts the patient behavior for a long term
(approximately 2 days). The model’s equilibrium corresponds
to a basal insulin injection level, and small disturbances desta-
bilize the system producing both, hyper and hypoglycemia
episodes, if no actions are taken.
The iZMPC has the following interesting features: i) im-
pulsive input due to the nature of the problem ii) artificial
variables, which give an enlarged domain of attraction (this
allows use a shorter prediction horizon), and in consequence
a reduced computational effort.
The control-variability grid analysis (CVGA) [6] is used for
measuring the quality of this closed-loop glucose control for
the cohort of patients. This method is for the visualization of
the extreme glucose excursions caused by a control algorithm
in a group of subjects, with each subject represented by one
data point for any given observation period. This analysis
shows that the iZMPC controller has a better performance than
the standard ZMPC because presents less hyper- and hypo-
glycemia episodes with less time outside to the normoglycemia
levels. Furthermore, it has a less pronounced peaks due to the
meals perturbations. The performance comparison shows that
the standard MPC is 70% of the time in the target zone, and
in contrast, the iZMPC is 92.5%.
This paper is organized as follows: Section 2 presents
the T1DM patient model. Sections 3 describes the discrete
and impulsive schemes, and the MPC formulation for both above this safety range), and hyperglycemia is dangerous long
strategies. In Section 4, numerical results are presented and term. Constraints for both, states and inputs are considered, in
the comparison developed. Finally, the conclusions and per- such a way that u ∈ U, x ∈ X and r ∈ R, where U, X and
spectives are discussed. R are assumed to be polyhedrons.
Furthermore, the insulin infusion u is considered as the
II. T YPE 1 DIABETES MODEL
control variable, while the carbohydrate (CHO) in meals r
According to [13], the following affine continuous time is considered as a disturbance. This disturbance, however,
model is considered: is neither a completely known nor a completely unknown
ẋ(t) = Ax(t) + Bu u(t) + Br r(t) + E, x(0) = x0 , (1) disturbance. In fact, in this work that disturbance is assumed
unknown, which avoids the alternative to predict or anticipate
where the state x(t) = [G(t) I(t) I(t)˙ D(t) Ḋ(t)]0 , being G the disturbance effect. A completely different problem arises -
the glycemia (mg/dl), I the plasma insulin (insulinemia) (U/l) mainly in the context of predictive control - if disturbances
and D the digestion of CHO (g/dl). Furthermore, u(t) the (meals) are assumed to be (even partially) anticipated by
control input, is the insulin infusion rate (U), and the variable means of a signal entering the controller. This issue is not in
r(t) is the food intake (g) and also is taken as the disturbance. the scope of this paper, but a perspective for future research.
The corresponding model matrices are given by:
0 −ksi 0 1 0
 
III. C ONTROL ALGORITHM DESCRIPTION
 0 0 1 0 0 
1 2
− − A. Discrete time scheme
 
A =   0 Tu2 Tu 0 0 , (2)

 0 0 0 0 1  The zero-order hold (ZOH) discretization is a standard
0 0 0 − T12 − T2r method used in ZMPC to obtain its necessary discrete-time
   r   
0 0 θ system [15]. Starting with the continuous model (1), the input
 0   0   0  u(t) is taken constant as
 ku     
Bu =   Vi Tu2  , Br =  0  , E =  0  ,
    
 0   0   0  u(t) = u(kTs ), kTs 6 t < (k + 1)Ts (3)
kr
0 VB Tr2 0
where (kTs ) corresponds to the actual sampling instant, (k +
where ksi represents the sensitivity to insulin, Tu and kVui 1)Ts is the next one, and k ∈ N. An analytical solution to
are respectively the time constant and static gain of the the continuous state-space model (1) considering this input is
relationship between the input u(t) (insulin rate) and the given by:
insulinemia I(t), with Vi being the insulin distributed volume,
and Tr and VkBr are respectively the time constant and static t
Z
A(t−kTs )
gain of the relationship between the CHO in meal r(t) and the x(t) = e x(kTs ) + eA(t−τ ) Bu u(τ )dτ (4)
kTs
digestion of CHO, D(t), with VB being the blood volume. Z t Z t
A(t1 −τ )
Furthermore, the parameter θ = k1 − kb is the difference + e Br r(τ )dτ + E eA(t1 −τ ) dτ.
between the liver endogenous glucose production k1 and the kTs kTs
glucose absorption rate by the brain kb .
If the latter equation is evaluated at t = (k+1)Ts , the discrete-
The main advantages of this model is that it is an integrating
time system is obtained, namely
model (A has an eigenvalue at zero, which means that it is not
stable) and so it better represents the evolution of the variable
in real life diabetic patients. For instance, any equilibrium x(k + 1) = Ad x(k) + Bud u(k) + Brd r(k) + Ed , (5)
point corresponding to the fasting state (rs = 0) is given
by an arbitrary value of G, fixed values for the other states, where the
R Tscorresponding discrete matrices are Ad = eATs and
A(Ts −τ )
∆ Bud = 0 e B dτ = A−1 (eATs −I)Bu , if A−1 exists,
and a fixed (and unique) value of insulin, us = ub , which R Ts A(T −τ ) u
is known as the basal insulin rate. These characteristics, that Brd = 0 e s Br dτ and Ed = E.
make the model essentially different from other models used
in the literature (mainly the Bergman model, [14]), allow us to B. Impulsive scheme
make long term predictions. This way, it is argued that every
undesirable episode can be better anticipated and corrected. If the insulin infusion u is assumed to be injected to the
∆
The general control objective is to maintain the glycemia system only at certain time instants given by τk = kT , where
in a safety range, X T ar , while keeping the other variables T is the fixed period, and k ∈ N, then it is possible to work
fulfilling the constraints, which are mainly positive values. under the impulsive system framework.
An interesting point is that the hypoglycemia episodes (when Formally, assume that the input is given by
glycemia is below this safety range) are more dangerous in
short time than hyperglycemia episodes (when the glycemia is u(t) = u(kT )δ(t − kT ), t ∈ [kT, (k + 1)T ], k ∈ N, (6)
where δ(t) is a generalized function (or distribution) Dirac 1) Underlying discrete time subsystems: According to the
delta1 , that fulfills δ(t) = ∞ for t = 0, δ(t) = 0 for t 6= 0, impulsive scheme developed in [11], two underlying discrete-
and time subsystems associated to (12) can be defined to charac-
terize the states x(τk ) and x(τk+ ) evolution2 :
Z ∞
g(ζ)δ(ζ)dζ = g(0), (7) x• (k+1) = A• x• (k)+Bu• u• (k)+Br• r• (k)+E • , x• (0) = x(τ0 ),
−∞
x◦ (k+1) = A◦ x◦ (k)+Bu◦ u◦ (k)+Br◦ r◦ (k)+E ◦ , x◦ (0) = x(τ0+ ),
for all continuous, compactly supported, function g. This way, ∆
the solution of (1) at each periods T can be divided into where A• = A◦ = Ad = eAT , Bu• = eAT Bu , Bu◦ = Bu .
two parts, the first one, describing the system in the period Furthermore, the input and disturbance are related by u◦ (k +
∆
[kT, kT + ∆T ], and the second one describing the system in 1) = u• (k) = u(τk ), r◦ (k) = r• (k) = r(k), and E • = E ◦ =
R T Aζ ∆ T
e dζE, Br• = Br◦ = 0 eAζ dζBr .
R
the period (kT + ∆T, (k + 1)T ), for a positive and arbitrary 0
small ∆: 2) Extended equilibrium for the impulsive representation:
The extended equilibrium points of the impulsive representa-
ϕ(t; x(kT ), u, r) = eA(t−kT ) x(kT ) (8) tion are characterized by the equilibrium points of the Under-
Z kT +∆T lying Subsystems, (x•s , u•s , rs• ) and (x◦s , u◦s , rs◦ ), respectively,
+ eA(t−ζ) Bu u(ζ)δ(ζ − kT )dζ in such a way that they must fulfill the conditions:
kT
Z kT +∆T
+ eA(t−ζ) Br r(ζ)dζ x•s = A• x•s + Bu• u•s + Br• rs• + E • ,
kT
Z kT +∆T x◦s = A◦ x◦s + Bu◦ u◦s + Br◦ rs◦ + E ◦ .
+ eA(t−ζ) dζE, So, the equilibrium sets corresponding to the two subsystems
kT
are given by
for t ∈ [kT, kT + ∆], and
∆
Xs• = {x•s ∈ X : ∃u•s ∈ U, rs• = 0 (13)
A(t−kT )
ϕ(t; x(kT + ∆T ), u, r) = e x(kT + ∆T ) (9) such that A• x•s + Bu• u•s + Br• rs• + E • = 0} ,
Z (k+1)T ∆
+ eA(t−ζ) Br r(ζ)dζ Xs◦ = {x◦s ∈ X : ∃u◦s ∈ U, rs◦ = 0 (14)
kT +∆T
Z (k+1)T such that A◦ x◦s + Bu◦ u◦s + Br◦ rs◦ + E ◦ = 0} ,
∆ ∆
+ eA(t−ζ) dζE, Us• = {u•s } = {u•b } , Us◦ = {u◦s } = {u◦b } . (15)
kT +∆T
Furthermore, given that u◦ (k + 1) = u• (k) and r◦ (k) =
for t ∈ (kT + ∆, (k + 1)T ). r (k) by definition (and E ◦ = E • ), we have that at steady
•
Now, if we consider the limits of this solution for ∆ → 0, state it is u•s = u◦s and rs• = rs◦ . For simplicity, the equilibrium
it follows that input and disturbance of both subsystems are denoted as u• (k)
and rs• , respectively. This means that it is necessary to find
∆
x(kT + ) = lim ϕ(t; x(kT ), u, r) = x(kT ) + Bu u(kT ), (10) variables (x•s , x◦s , u•s , rs• ) fulfilling
∆→0

and x•s = A• x•s + Bu• u•s + Br• rs• + E • , (16)

x◦s = A◦ x◦s + Bu◦ u•s + Br◦ rs• + E • . (17)
∆
x(t) = lim ϕ(t; x(kT + ), u, r) = eAt x(kT + ) (11)
∆→0 A final condition that the equilibrium quadruplets
Z (k+1)T Z (k+1)T
A(t−ζ) A(t−ζ) (x•s , x◦s , u•s , rs• ) must fulfill to be a feasible extended equi-
+ e Br r(ζ)dζ + e dζE,
kT + kT + librium, is that the free response corresponding to them (the
orbit) must be feasible:
for t ∈ (kT + , (k + 1)T ). This latter solution is the one
corresponding to the continuous time system ẋ(t) = Ax(t) + os (x•s , u•s , rs• ) ∈ X ,
Br r(t) + E, x(0) = x0 . So, the hybrid system evolution can
be described as an impulsive system of the form: where
∆
 os (x•s , u•s , rs• ) = {φ(t; x•s , u•s (t), rs• (t)), t ∈ [τk , τk+1 ), k ∈ N} ,
 ẋ(t) = Ax(t) + Br r(t) + E, x(0) = x0 , t 6= τk ,
(12) u• (t) is the impulsive input and r• (t) the constant disturbance,
 x(τk+ )= x(τk ) + Bu u(τk ), k ∈ N. s s
in a period T , i.e. u•s (t) = u•s δ(t − τk ) and rs• (t) = rs• , for
1
t ∈ [τk , τk+1 ), k ∈ N.
The Dirac delta is only an abstraction to formulate the impulsive problem.
The idea behind this concept is that quick insulin injections can be properly
approximated by impulses, if compared to T . 2 The state x(τk ) is denoted as x• (k), while x(τk+ ) is denoted as x◦ (k).
 In this context, we can characterize the extended equilibrium where
by redefining the equilibrium set Xs• as3 N
X −1
T
∆ Vdyn (x, r; u, ua , xa ) = (x(j) − xa ) C 0 QC (x(j) − xa )
Xs• = {x•s ∈ X : ∃u•s ∈ U, rs• = 0 such that j=0
A• x•s +Bu• u•s +Br• rs• +E • = 0, os (x•s , u•s , rs• ) ∈ X } (18) +
T
(u(j) − ua ) R (u(j) − ua ) , (21)
Furthermore, Us•
is a singleton for the diabetes system, i.e. with Q > 0 and R > 0, is a term devoted to steer the system
• ∆ • •
Us = {us } = {ub } = 6 {ub }. to a certain artificial open-loop equilibrium variable given by
The same procedure can be followed to define the equilib- the artificial pairs (ua , xa ) ∈ Us• × Xs• , and
rium sets corresponding to the target or therapeutic window,
∆
Xs•T ar and Us•T ar = {u•b }. Vf (Xs•T ar , UsT ar ; ua , xa ) = p distCXs•T ar (Cxa )


+ distUs•T ar (ua ) (22)
C. Zone MPC formulation
with distD (·) being the distance from a point to a set D, and
In this section the ZMPC formulations is stated for the
p > 0, is a terminal cost devoted to steer Cxa to the target
standard version and the impulsive scheme [12].
sets CXs•T ar and ua to Us•T ar , respectively.
1) Discrete zone MPC: Te main objective of the ZMPC
The optimization problem to be solved at time k by the
is to compute the future inputs that minimizes the distance
MPC is given by
from a predicted system trajectory (over a finite horizon) to
the target zone (chracaterized by X T ar and the corresponding
PM P C (x, r, Xs•T ar , Us•T ar ):
U T ar ). The cost function to be minimized, has the following
form: [7]: min VN (x, r, Xs•T ar , Us•T ar ; u, ua , xa )
u,ua ,xa
N
X s.t.
min J = k (y(j) − yref − δ) k2Q x(0) = x,
u,yref ,uref
j=1 x(j + 1)=A• x(j)+Bu• u(j)+Br• r(j)+E • , j ∈ I0:N −1
N
X x(j) ∈ X , u(j) ∈ U, j ∈ I0:N −1
+ k (u(j) − uref ) k2R (19) x(N ) = xa ,
j=0 xa ∈ Xs• , ua ∈ Us• .
s.t.
where as it was already said, u = {u(0), u(1), · · · , u(N − 1)}
x(0) = x and r = {r(0), r(1), · · · , r(N − 1)}. The constraint x(N ) =
x(j + 1) = Ad x(j) + Bd u(j) + Brd r(j) + Ed , j ∈ I0:N −1 xa is the terminal constraint that forces the terminal state
- at the end of control horizon N - to reach the artificial
y(j) = Cx(j), u(j) ∈ U, x(j) ∈ X , j ∈ I0:N −1 equilibrium state xa . Furthermore, the last constraint forces
T ar T ar
yref ∈ CX , uref ∈ U , |δ| ≤ δmax , the artificial variable pair (ua , xa ) to be in Xs• × Us• , and it is
equivalent to force the pair (ua , xa ) to fulfill the equilibrium
where u = {u(0), u(1), · · · , u(N − 1)}, y(j), j ∈ I0:N −1 ,
condition xa = A• xa + B • ua . This means that the state at the
is the predicted output sequence, uref and yref are extra
end of the horizon is only forced to be any feasible equilibrium
optimization variable that are in the input and output target
state [11].
zones, and δ is a slack variable bounded by δmax . The
matrices Q and R determine the deviation of the output and IV. I N SILICO :N UMERICAL RESULTS
control, respectively. The constraints are the discretization of
The simulation was performed based on the data of 20
the model, the control and state bounds, and state target.
virtual patients taken from [13] and also provided by the
Matrix C is an output matrix that decides which states will be
‘Centre Hospitalier de Nantes’. The main objective is to carry
controlled.
out the glycemia to the normoglycemia zone, thereafter, the
2) Impulsive Zone Model Predictive Control (iZMPC): The
second objective is to maintain the system inside these limits
therapeutic window is characterized - for the impulsive scheme
even when strong ‘perturbations’ (as food intake) enter to the
- by sets Xs•T ar and Us•T ar while Xs• and Us• denote the
system.
equilibrium sets. The proposed MPC formulation is the one
Both strategies are tested using the T1DM patient model
described in [11], adapted to the integrating affine system (1).
described above, together with the constraints and the target
The cost of the optimization problem that MPC solves on-line
window. The simulation horizon is settled in 50 h. This horizon
is
is larger than the one used in other works [16]–[18], since the
∆ used linear model is able to reproduce accurately the behaviors
VN (x, r, Xs•T ar , Us•T ar ; u, ua , xa ) = Vdyn (x, r; u, ua , xa )
•T ar •T ar for long-time intervals. In spite of the simplicity of the model,
+Vf (Xs , Us ; ua , xa ), (20)
this is an advantage when control strategies are designed.
3 Note that condition (13) (and (17)) is implicitly accounted for definition The performance of the control strategies is tested on a 2-
(18). day virtual protocol. For each patient is considered different
 TABLE I
>400 SUMMARY OUTCOME

Upper C Upper D E ZMPC mode A A+B C+D E

Discrete 17.5% 70% 27.5% 2.5%
Maximum BG

Impulsive 60% 92.5% 7.5% 0%

300

Upper B B Lower D TABLE II

I N - SILICO PERFORMANCE RESULTS
180 ZMPC strategy Impulsive Discrete
∈ [80, 140] 89.74 67.24
A Lower B Lower C ∈ [70, 180] 94.50 83.57

BG [mg/dL] % time
< 80 0.67 13.96
< 70 0.11 6.11
<110
>110 90 70 <50 < 60 0.00 4.08
< 50 0.00 3.41
Minimum BG > 180 5.37 10.30
> 250 3.35 6.66
Fig. 1. CVGA for patients controlled by discrete ZMPC (dots) and impulsive > 300 2.80 5.69
ZMPC (open circles). > 350 2.42 2.80
> 450 1.81 0.45
< 80 6 1

# Events BG [mg/dL]
< 70 4 0
scenarios, since the patients are assumed hospitalized, regular < 60 1 0
meals are considered: the breakfast, the launch, the dinner, and < 50 0 0
< 40 0 0
some snacks between meals. > 180 50 77
The state and input constraints are given by X = {x : > 250 11 19
[0 0 − 0.1 0 − 0.1]T  x  [500 .5 0.1 1 0.1]T } and > 300 5 14
> 350 1 10
U = {u : 0 ≤ u ≤ 30}, respectively. The state target window > 450 0 4
should be decided by the treating physician. In the simulation BG [mg/dL]: Mean 121.89 152.9297
below it is defined by X T = {x : [80 0 − 0.1 0 − 0.1]T  BG [mg/dL]: Min 66.00 9.5135
BG [mg/dL]: Max 390 470.8716
x  [100 0.2 0.05 0.5 0.05]T }. It is clear that, if the glycemia
remains most of the time within the boundaries of X T , then
the insulin therapy is satisfactory. the performances of the discrete and impulsive ZMPC, the
The therapeutic windows (target zone) for the glycemia summary outcome presented in Table I for iZMPC shows an
values is selected to be [80 − 100], which is a zone strictly accurate control in the 60% cases and a benign control for the
inside the normoglycemia zone of [60 − 140]. This is so 92.5% and also, only have two cases in over-correction and
to improve the performance, since the controller makes no one case in failure to deal with hyperglycemia, and zero cases
distinction between points inside the zone, and so, it tends in the zone of hypoglycemia. The summary outcome I for the
to maintain the glycemia at the boundary of the therapeutic discrete ZMPC shows a regular accurate control 17.5% and
window (not at a middle point) that is closer to the current a benign control for the 70%; however, this strategy shows a
value. If a disturbance pushes the system above the zone, the 20% over-corrections of hyper- and hypoglycemia and a 7.5%
controller only steers the system back to the upper bound of of failure to deal with hypoglycemia and one case of erroneous
the zone. As a result, any disturbance in the same direction control. See also Table 2. Figures 2-5 shows the evolution of
will produce a transitory evolution that can take the glycemia glycemia and the control effort for paciente IF2 (see [13]).
far from the upper bound. So selecting the bounds of the target
zone inside the normoglycemia zone could be a good practice. V. C ONCLUSIONS
For the iZMPC, the control/prediction horizon N should be A comparison of the performance between discrete and
large enough to account for the entire insulin effect (given impulsive form on the design of ZMPC for the regulating
that overdoses are hard to compensate, because of its posi- glycemia in type I diabetic patients has been tackled in this
tiveness). So, according to the insulin response settling time, paper. The main differences between this ZMPC controllers
the control/prediction horizon (which is the number of periods are: i) the iZMPC controller do not need a permanent insulin
considered for the predictions) is selected in these simulations injection in contrast to the discrete ZMPC, and the insulin
to be N ≈ STuT×60 , which is only a practical rule. Note is delivered by boluses, preventing insulin overdoses, ii) both
however that, as it is usual in MPC, the use of larger horizons controllers can maintains the glycemia levels in the normal
N needs a high computational effort. The iZMPC parameters range (70 ∼ 140mg/dl) but the iZMPC obtain a better
are selected to be: Q = 500; R = 1; p = 500000. A detailed regulation of the glycemic in the accurate zone (see Fig 1)
analysis for the selection of these parameters, according to the thanks to the artificial variables.
patient parameters, still needs to be done. In general, the CVGA analysis showed that the iZMPC
In the Fig 1, the CVGA method is applied to compare controller had a better performance to maintain the glucose
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less strict zone (70 mg/dl − 300 mg/dl), and with a risk of
hypoglycemic/hyperglycemic episodes.
The main drawback of ZMPC is the tuning of its parameters,
whose task may be not trivial. This set-up allows it a variety of
closed-loop behaviors, and several studies can be done to find
a method to tune the controller according to the significant
model parameters of the patient, that will be pursued in a
future work.
The simulations has good results in these small cohort of
virtual patients; however, for future studies it is important to
perform a validation with a larger cohort of patients, especially
those brought by the FDA (Food and Drug Administration)
accepted ‘UVA/Padova’ simulator of diabetic patients.
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