H-infinity controller design for Blood Glucose
Regulation in Diabetes Patients in the Presence of
Uncertain parameters
HACHANA Aicha
Electrical Engineering, Laboratory LAS
University Setif 1
Setif, Algeria
hachana_ai@yahoo.fr
Abstract— This paper presents deals with uncertain description
of a system for a type I diabetes mellitus patient under an
intensive insulin treatment .The control algorithm employs a
robust H’ controller to regulate the blood glucose level in
diabetic patients. Diabetes mellitus is a kind of chronic metabolic
diseases in which body’s blood glucose regulatory system doesn’t
function properly. In this study, Bergman’s minimal model has
been used as a base model, to increase the functionalities of the
glucose minimal model, some additions could be done. One of the
additions is the exercise model and since it is hard to derive exact
value of parameters in most biological systems, all parameters of
the model has been considered uncertain and therefore
parametric uncertainty has been exploited in control design .The
control scheme is based on closed-loop feedback strategy. The
behavior of the obtained controller was analyzed on ability to
track a normoglycemic set point of 81mg/dl in presence of
disturbance and course tracking of the closed loop with the
nominal system and the system with perturbed parameters. The
designed controller proved effective in achieving normoglycaemic
and robust to meal and exercise disturbances.
Keywords—Type I diabetes; Robust H’ controller; Insulin
Delivery rate; exercise model; Glucose Regulation; parametric
uncertainty.
I. INTRODUCTION
Diabetes mellitus (DM), commonly referred to as diabetes,
is a group of metabolic diseases in which there are high blood
sugar levels over a prolonged period. Symptoms of high blood
sugar include frequent urination, increased thirst, and
increased hunger. If left untreated, diabetes can cause many
complications. Today, you treat the patients, through injection
of insulin. These injections are made with different devices,
syringes, pumps etc. The problem with the devices today, is
that they all have to be controlled by the patient. And the
injections is not always done when actually needed. A perfect
solution to the problem would be to create a treatment type,
where the patient, doesn’t have to think about having diabetes.
This could be a self-regulated pump acting like an artificial
pancreas. [2], [4]. Fig (1) shows the block diagram of closed
loop control of diabetic patients using insulin pumps.
During the last decades, many mathematical models have
been derived to describe dynamics of glucose-insulin
ABDELAZIZ Mourad
Electrical Engineering , Laboratory LAS
University Setif 1
Setif, Algeria
abde_m@yahoo.fr
regulatory system [7-21]. The glucose-insulin system is an
example of a closed-loop physiological system.
Exercise Blood
Meal glucose
Infusion
level
ref Error rate +
R Pum Patien
Insulin
Measured blood
glucose level
Fig. 1. Closed-loop of diabetic patients.
For tighter glucose control, the current focus is on the
development of automated closed-loop insulin delivery
systems. In a model-based control algorithm, should be robust
to physical disturbances like food intake .Some of these
algorithms contain pole placement [11], proportional-
derivative (PD) [10], proportional-integral-derivative (PID)
[9], and optimal control algorithms [12, 13]. Some articles are
used H’ controller [6,8,14,20]. the H’ control is well suited
for our system, due to the ability to tune the controller to
robustness and guarantee a certain degree of performance [15].
But full robustness cannot be achieved via these articles.
Since they based on the exact value of parameters, it is hard to
derive exact value of parameters in most biological systems,
all parameters of the model has been considered uncertain and
therefore parametric uncertainty has been exploited in control
design .The control scheme is based on closed-loop feedback
strategy. In this work, we use the Bergman’s minimal model
[7]. To increase the functionalities of the glucose minimal
model, some additions could be done. One of the additions is a
function describing what an exercise would do to the glucose
level. [3]
In this paper we have discussed a new problem is the
presence of uncertain parameters in the Bergman’s minimal
model ,exploits H’ control method to regulate the blood
glucose level of type I diabetes mellitus patient around
euglycemia with a closed-loop system, callous to internal and
external disturbances, precision, and robustness to uncertainty.
The paper is organized as follows: In section II the disturbances and stabilize blood glucose level of diabetic
physiological model of glucose-insulin regulatory system in patient at basal level.
type I diabetes mellitus patient is introduced and detailed.
A. Linear Model
Section III includes the synthesis of the H’ control. Simulation
results and concluding remarks are included in sections IV and Bergman mathematical model is a nonlinear model, which
V, respectively. become linear around steady state values to design closed-loop
II. INSULIN-GLUCOSE REGULATION MODEL controller of the model. It can be linearized using Taylor’s
expansion around the equilibrium G=Gb ,X=0 and I=Ib .
Bergman’s minimal model is a one compartment model,
The system introduced in equation (1) can be rewritten in
meaning that the body is described as a compartment/tank
state-space form as follows
with a basal concentration of glucose and insulin [7]. ⋅
The Bergman minimal model consists of three differential x1 = − p1 [ x1 − G b ] − x1 x 2 + D ( t )
equations as follows: .
⋅
G ( t ) = − p1 [ G ( t ) − G b ] − X ( t ) G ( t ) + D ( t ) x2 = − p1 x2 + p3 [ x3 − I b ]
(3)
⋅ ⋅
X ( t ) = − p 2 X ( t ) + p3 [ I ( t ) − I b ] x3 = −n [ x3 − I b ] + γ [ x1 − h] t + u (t )
+
(1)
⋅
I (t ) = − n [ I (t ) − I b ] + γ [G (t ) − h ] t + u ( t )
+
x ,x x
Where 1 2 and 3 are blood plasma glucose concentration
(mg/dl), the insulin’s effect on the net glucose disappearance
Compartment I(t), X(t), and G(t) represent the plasma (1/min) and the insulin concentration in plasma
insulin (ȝU/ml), remote insulin (ȝU/ml), and plasma glucose (ȝU/ml),respectively. Note that the term Ȗ[G(t)íh]+ is
concentration (mg/dl),respectively. Ib and Gb are the basal removed from (1) as it does not exist in diabetic patients [17],
plasma insulin and glucose concentrations, respectively, The [22],one can write continuous-time nonlinear differential
rate constant n represents clearance of plasma insulin (1/min), equations in this form:
h is the threshold value of glucose above which the pancreatic
⋅
ȕ - cells release insulin (mg/dl) and Ȗ is the rate of the
x(t ) = f ( x(t ), u (t ), t )
pancreatic ȕ- cells’ release of insulin after the glucose
injection with glucose concentration above the threshold y (t ) = g ( x(t ), u (t ), t )
[(μU/ml min -2 (mg/dl) -1 ], the term, Ȗ[G(t)-h]+ acts as an ⋅
internal regulatory function that formulates the insulin x1 = − p1 [ x1 − Gb ] − x2 x1 + D(t )
excretion in the body, which does not exist in diabetic ⋅
patients. It has been also argued in [17], [18] .The parameters x 2 = − p 2 x 2 + p 3 [ x3 − I b ] (4)
of the model and their values are introduced in [17] and [18].
⋅
It is worth noticing that all the values are computed for a
x3 = −n [ x3 − I b ] + u (t )
person of average weight and these are not constant numbers
and vary from patient to patient. In these equations, x(t) represents the system states
To show the complete dynamics of the glucose-insulin x
( 1
= y = G , x 2 = X , x 3 = I ) , u(t) represents the
regulatory system, two other terms are considered in equation inputs to the system, and y(t) represents the outputs of the
(1). To increase the functionalities of the glucose minimal system.
model, some additions could be done. One of the additions is a A linearized model of this system is valid in a small region
disturbance signal D(t) .This disturbance can be modeled by a around the operating point t=t0, x(t0)=x0, u(t0)=u0, and
decaying exponential function of the following form: y(t0)=g(x0,u0,t0)=y0
To represent the linearized model, define new variables
D(t)=Aexp(-Bt),B>0 (2) centered about the operating point:
*Terms of the exponential form Ȗ exp(í0.05t), which Substituting in, using the constant and deviation variables,
represent the standard Fisher meals [18]. we get
*Terms of the exponential form İ exp(í0.025t), which
represent larger random effects due to factors such as exercise δ x (t ) ≈ f ( x, δ x (t ), u, δ u (t ))
(5)
or strong emotions [3]. This is exact .now however, let’s do a Taylor expansion of
Where t is in min and D(t) is in (mg/dl/min). u(t) is the the right hand side, and neglect all higher order terms
exogenous insulin infusion rate. The controller uses feedback .
∂f ∂f
loop that employs the blood glucose level G, and its derivative δ x (t ) ≈ f ( x , u ) + ∂x x = x δ x (t ) + ∂u x = x δ u (t )
(dG/dt), as sensor inputs, and the exogenous insulin infusion u =u u =u
(6)
rate u(t) as the control output. The controller defines the
insulin infusion rate, u(t) to compensate the uncertainties and But f ( x, u ) =0, leaving
 .
δ x (t ) ≈ ∂∂fx x= x δ x (t ) + ∂∂uf x=x δ u (t ) The values of Table 1 are used to define uncertain
u =u u =u
(7) parameters [24].
It can be assumed that their values are within certain,
known intervals. That is,
A := ∂∂fx x= x ∈ℜn×n B := ∂∂uf x= x ∈ℜn×m
( ) ;i=1,2,3.
u =u u =u
pi = pi 1 + rpi δ pi
(10)
∂g p×n ∂g p×m
C := ∈ℜ D := ∈ℜ
∂x x = x
u =u
∂u x = x
u =u
n = n (1 + rnδ n )

The linearized model in terms of įx, įu, and įy is valid when pi n are the so-called nominal values of pi and
Where and
the values of these variables are small:
rpi rn δ pi δ n represent the possible (relative)
. , , and
δ x(t ) = Aδ x(t ) + Bδ u (t ) perturbations on these parameters.
We note that the quantity n may be represented as an upper
δ y (t ) = Cδ x(t ) + Dδ u (t ) (8) a linear fractional transformation (LFT) in įm
.
n = Fu ( M n , δ n ) ;
x1 = − p1 x1 − Gb x2
. ª 0 nº
x 2 = − p 2 x 2 + p 3 x3
(9) With M n = « ».
.
«¬ rn n »¼
x3 = − nx3 + u (t ) Similarly, the parameter pi
Where A =state matrix, B =input matrix, C =output matrix pi = Fu ( M pi , δ pi )
and D = feed through (feed forward) matrix.
ª0 pi º
B. Model of the diabetic patients with uncertain With M p = « ».
«¬ rpi pi »¼
i
parameters

The goal of the uncertain model is to cover possible

difference between the model and the reality by defining the ªδ pi 0º
uncertainty for selected parameters. « »
¬0 δn ¼
The following is diabetic patients model with uncertain
parameters based on description (9) and principles of
uncertain modeling [21].
u G y
TABLE I. RANGES OF PARAMETER VALUES FOR REALISTIC PATIENTS
Fig. 2. LFT representation insulin-glucose system with uncertainties
Parameter Min Value Max Value
P1 0 0
P2 0.01 0.02
P3 1.0*10-6 3.0*10-6
n 0.12 0.3
u x3 + x2 x1
+
™
œ Mp3 ™ œ Gb _ ™
œ
- - _

Mn δp M p2 M p1
up3
3
y
p3

δn δp y
y un y 2 up2 p1 δp
n p2
1
up1
Fig. 3. Block diagram of the diabetic patient system.
 The G matrix represents the augmented system obtained uncertainty model respectively.The transfer matrix P(s)
from the nominal system and ǻ matrix represents variations of is expressed as:
the system parameters. The ǻ matrix is a diagonal matrix
ǻ = diag{įp1, . . . , įn} in case of the parametric uncertainty. ¨
The augmented model G is typically obtained by upper linear
w¨ z¨
transformation [16].
The equations governing the system dynamic behavior are
given by:
w P(s) z
y
ªx º ª
« 1 » «− p1 −Gb 0 −r p 0 0 0 0 º» ª x1 º u
«x » « 1
« »
« 2» «0 − p2 p3 0 −r p rp 00 »» «« x2 »» K(s)
«x » «
« 3» «0
2 3
»
0 −n 0 0 1 » «« x3 »»
0 −rn Fig. 5. H’ synthesis problem.
«y » « »
« p1» « p 0 0 0 0 0 0 0 » ««u p »»
« »=« 1 »
1
ªA B1 B2 º
«yp » « p2 0 0 0 0 0 0 » ««u p »»
« 2» « 0 »«
2
P ( s ) = «« C1 D11 D12 »»
«y » « »
« p3» « 0 0 p3 0 0 0 0 0 »» «u p » 3 «¬C2 D21 D22 »¼
« » « « » (11)
«y » « 0 0 n 0 0 0 0 0 »» «un » Thus the plant transfer matrix P is related with the input
« n» « « »
«y » ¬1 0 0 0 0 0 0 0 »¼ ¬«u ¼» and output vectors as:
¬ ¼
ª zΔ º ª wΔ º
C. Selection of Weighting functions « z » = P« w »
The weighting functions involved in the block diagram of « » « »
Fig.4. corresponds to the meal disturbance weight (Wm), «¬ y »¼ «¬ u »¼
exercise disturbance weight (Wex) and performance weight (12)
(Wp). the control input weight (Wu), The control input weight The controller synthesis for the suboptimal H’ case is
is taken as Wu=1, which is reasonable for the present system formulated as follows: given Ȗ >0, find an internally
[19]. stabilizable controller K(s), if there exists any, such that ,
1 1 Gzw Eγ
Wex ( s ) = Wm ( s) = ∞ where Gzw is the closed-loop transfer matrix from
2s + 1 5s + 1 w to z and given by:

s Gzw = Fl ( P, K )
+ 0.5 (13)
A first order Wp has been chosen: W p ( s ) = 2 In order to find the controller, if exists, P(s) should satisfy
s + 0.05 the following conditions [19, 20]:
ex • (A, B2) is stabilisable and (C2, A) detectable;
m
Z2 z Δ
Wm Wex z1 • D12 = [0 I]T andsD21 = [0 I];
Wu
Wp
Ref G
ª A − jω I n B2 º
K « C D12 »¼
• ¬
+ y 1
has full column rank for all Ȧ;
- ª A − jω I n B1 º
n « C D21 »¼
• ¬ 2
has full row rank for all Ȧ.

Fig. 4. Standard feedback with weights.Parameter Uncertainty configuration For the system in the present study the assumptions are
satisfied. The system of two Riccati equations is solved
through the Ȗ-iteration technique.
III. ROBUST CONTROL SYNTHESIS USING H’ APPROCH
The closed loop system must satisfy the following constraint
In this section we provide a self-contained route to M:
solve the H’-problem.can be recast into a standard
configuration as in Fig.5. P(s), K(s) and ¨ are the transfer
matrices of the plant and the controller and the system
 ROBUST STABILITY
-2
10
upper bound
lower bound
W (I + KFu (G, Δ))−1Wm Wp (I + KFu (G, Δ))−1Wex WpKFu (G, Δ)(I + KFu (G, Δ))−1
M= p <γ
-3
10
−1 −1 −1
u (I + KFu (G, Δ)) Wm WK
WK u (I + KFu (G, Δ)) Wex u (I + KFu (G, Δ))
WK
Where
-4
10

mu
§ m ·
§ Z ·
-5

¨ ¸
10
¨
1
¸ = M ¨ ex ¸
© Z 2 ¹ ¨ n ¸
© ¹ 10
-6

IV. SIMULATION RESULTS 10 -1

10
-7

10
0
10
1
10
2

Frequency (rad/sec)

The frequency responses of the upper and lower bounds of ȝ

are shown in Figure 6. It is clear from the figure that the
closed-loop system with K achieves robust stability. The Fig. 6. Robust stability analysis.
maximum value of ȝ is 0.0082258 which shows that structured Robust Performance

0.545
perturbations with norm are less than 1. upper bound
0.54
The frequency responses showing the robust performance is lower bound
0.535
given in Figure 7. It is seen from this figure that the system
0.53
with K achieves robust performance. The maximum value of ȝ
is 0.539 which shows that structured perturbations with norm 0.525

are less than 1.To check the robustness of the control

mu
0.52

algorithm to the parameter variations. Simulations are done for 0.515

three different diabetic patients, where Table .2 [23] shows 0.51

model parameters for these patients, taken from [18]. Fig.8 0.505

and Fig .9 shows the results obtained from the simulation It is 0.5
obvious that the glucose concentration levels of the patients 0.495 -1 0 1 2

are finally stabilized at the basal level (81mg/dl) 10 10

Frequency (rad/s)
10 10

The glucose level control of diabetic patients, the result of

Fig. 7. robust performance.
three meals were considered per day: breakfast (8am), lunch
(2pm) and dinner (8pm) ,value of 60gm (CHO) for 15min and 350
an exercise disturbance of 0.05 arbitrary units at 5pm for Patient 1

20min duration. The reference plasma BG level is considered 300

Patient 2

Patient 3
as 81mg/dl. Though the insulin dispensing apparatus has a
capacity of pumping rate 0mU/min< u(k)< 133mU/min as per 250

device data [19].

m g/dL

200
Fig. 10 and Fig .11 shows the 24-hour glucose-insulin
level control of diabetic patient using H’ controller. The BG 150
level of the patient is finally stabilized at the basal level
(81mg/dl) in a reasonable time interval. When the patient is 100
submitting to specific exercise disturbance, the glucose level
falls to 67 mg/dl, which is also within satisfactory limit. 50
0 100 200 300 400 500 600 700 800 900 1000
Time (min)

TABLE II. BERGMAN MINIMAL MODEL PARAMETERS.

Fig. 8. Glucose concentration.
Variable Patient 1 Patient 2 Patient 3 Units
P1 0 0 0 1/min
25
P2 0.0142 0.0172 0.02 1/min Patient 1

P3 2.4x10-6 2.16x10-6 3x10-6 ml/uUmin2 Patient 2

n 0.2814 0.2465 0.3 1/min 20 Patient 3

15
m icroU/mL

10

0
0 100 200 300 400 500 600 700 800 900 1000
Time (min)

Fig. 9. Insulin concentration.

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pancreas for treatment of diabetes”, Diabetes Care,Vol. 21, pp. 444-
96 450, 1998.
patient
94
[3] Mihalis G. Markakis, Georgios D. Mitsis” A switching control strategy
normal
for the attenuation of blood glucose disturbances”, Optim Control Appl
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90
“An artificial endocrine pancreas”, Diabetes Care,Vol. 23, pp. 389-396,
88 1974.
m g/dL

86
[5] A.G.Gallardo, L.Fridman” High-order sliding-mode control for blood
84 glucose: Practical relative degree approach’’ ,Control Engineering
Practice 21 , 747–758, 2013.
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on Systems in Medicine and Biology 16-18 Dec 2010.
78
0 500 1000 1500 [7] R. N. Bergman, L. Philips, and C. Cobelli, "Physiological evaluation of
Time (min) the factors controlling glucose tolerance in man", J Clinical
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Fig. 10. BG response of the closed-loop system.
in mans its use to design and assess improved insulin therapies for
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m icroU /m L

8
7.5
7
6.5
0 500 1000 1500
Time (min)
Fig. 11. Insulin Infusion response of the closed-loop system.
V. CONCLUSION
Diabetes is a widespread disease in the western world
today. Many researchers are working on methods for treating
diabetes in the domain of human regulatory systems. The
article presents approach for the robust H’ controller design to
regulate the blood glucose level in diabetic patients .The
approach is based on uncertain model of the system. It was
tested in a simulation and it was proved that the controller is
able to stabilize even the most degraded model within the
given uncertainty range. The performance purpose was to
regulate the glucose level in face to disturbances depicted by
known meals and excise. The glucose-insulin response has
shown the results obtained from the simulation, it is obvious
are finally stabilized at the basal level in a reasonable time
interval. Future work is lead to the employing of the μ
synthesis.
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