1313

ADAPTIVE LQG/LTR CONTROLLER FOR

IMPLANTABLE INSULIN DELIVERY SYSTEM
IN TYPE-1 DIABETIC PATIENT
A. Sutradhar
Department of Electrical Engineering
Bengal Engineering College (D. U.)
Howrah 711 103. INDIA
E-mail: asee1@rediffmail.com

A.S. Chaudhuri
Department of Electrical Engineering
Dr. B. C. Roy Engineering College
Durgapur 713 206, INDIA
E-mail: aschaudhuri@hotmail.com

Key words: Diabetes Mellitus, Glucose-insulin interaction, Implantable pump, Controlled drug delivery, LQG/LTR control, Disturbance rejection

The instrumentation and closed loop adaptive control of blood glucose concentration
in diabetic patients have become very much important issue for the present day biomedical engineers. Controlled drug delivery is used to administer the optimum dose of
the drug for the treatment of diabetes and many other chronic clinical disorders requiring continuous medication for an extended period of time. In this paper, a linearized model of the diabetic patient with the implanted insulin delivery device has
been utilized to design adaptive LQG/LTR controllers for the blood glucose regulation with the rejection of periodic or random meal and exercise disturbances to the
process. The continuous-time and discrete-time designs have been compared and the
robustness of the controllers has been established.

1. Introduction
The issue of continuous and controlled drug delivery is important for the treatment of many chronic clinical disorders requiring medication for a long period. Most
drugs whether taken orally or via injection are delivered to the body system-wide.
Site-specific drug delivery allows medication directly into the blood stream at a programmed rate to achieve the optimum dose as a function of time [1]. With controlled
drug delivery system, the patient requires as little as 1% of the equivalent oral dosage
to experience the same level of relief. Programmable implantable medication systems
are useful for administration of morphine sulfate to treat chronic pain, baclofen to
treat severe spasticity of both spinal and cerebral origin, clindamycin to treat osteomyelitis, and several drugs in chemotherapy [2]. Multiple drugs (dopamine and sodium nitroprusside) are used to regulate the mean arterial pressure and cardiac output
under different patient conditions like congestive heart failure, post-operative hypertension and sepsis shock etc. The effects of the multiple drugs on the patient are also
coupled [3]. Though there are various areas of applying implantable drug delivery systems, a broad area is administering insulin in diabetic patients [4].

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An estimated 135 million people worldwide suffer from fluctuating blood glucose
levels out of which at least 15 millions are in India [5]. Closed loop control of insulin
delivery is required to maintain exact timing and dose of the drug [2, 4, 6] to counter
the blood glucose level. Disease responsive, feedback control-based devices require
the operation or function of electrical and mechanical parts with on-line measurement
of physiological variables of the body, blood or other biological fluids. Though extensive research is going on in the field of biomaterials for fine particle transport applied
to drug delivery [7] and biocompatible devices and sensors [8], development of control algorithms giving adaptive and robust performance in presence of disturbances
and uncertainties in the process is also important [24, 6, 9]. Several such control
strategies for controlled drug delivery have been discussed in literatures [3, 915].
The closed loop insulin therapy involves the interplay between the natural dynamics of the physiological process, the stochastic nature of the uncertainties and the effects of the deterministic command inputs. In this paper, we address some adaptive
controllers for insulin delivery system in a diabetic patient to regulate blood glucose
level rejecting the meal and exercise disturbances and the sensor noises of periodic or
random nature. The vehicle that we use for the present physiological process is the
adaptive linear quadratic Gaussian (LQG) optimal control and estimation of states
(Kalman filtering). Despite the merits of LQG controllers, to this day still there is a
void of published work in practical design and implementation issues on LQG methodology in implantable insulin delivery system for blood glucose regulation. Very few
deals with discrete time issues of LQG design; a focus is also made in this direction.
We do not discuss the LQ theory, which can be consulted for details in Athans [16],
Doyle et al. [17], Anderson et al. [18], strm et al. [19] and Glad et al. [20] etc. A
9th order linear non-minimum phase state-space model of the patient with the implanted device has been considered and the disturbance model has been formulated to
apply continuous time and discrete time LQG methods. Stability and robustness of the
closed loop system has been established by using loop transfer recovery (LTR) methods.

2. Problem formulation
2.1. Closed loop system overview
The closed loop drug delivery system in diabetic patient necessarily contains a
patient model estimator, which continually estimates the patient states in recursive
manner from the nonlinear process with uncertainties and disturbances. Meal and exercise are considered as the disturbance inputs to the process. The sensor noise is considered separately. The block diagram of the overall system is shown in fig. 1.

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Meal + Exercise
Disturbances (white noise)
Ref=0
+

Insulin command

LQG / LTR
CONTROLLER

DIABETIC PATIENT WITH

IMPLANTED
+ INSULIN PUMP

LINEAR PATIENT
STATE ESTIMATOR

Sensor Noise
+
+

Measured
Arterial
Glucose

Ref
Glucose
Level

Fig. 1. Block diagram of blood glucose regulation by LQG control

2.2. Clinical Background

Diabetes Mellitus is a group of clinical disorders characterized by chronic high
level of arterial blood glucose (BG) exceeding 144mg/dl, called hyperglycaemia. It is
caused either by the deficiency of insulin hormone in the body, or the resistance of it
or both [21, 22]. This occurs when the body is unable to use glucose effectively. In
type-1 diabetes, the patients system is completely unable to produce insulin and in
type-2, insulin is produced at a smaller rate and its action is also inhibited. Despite the
varying demands of food, fasting and exercise, BG levels are very tightly regulated in
the body.
Glucose is the main source of energy we need for the normal activities of our life.
It is absorbed in the circulation from our food (mainly carbohydrate) at various parts
of our digestive system, generally termed as gut. This is the external source of glucose in circulation. The venous blood draining the gut absorbs glucose and transports
it to the liver. Glucose is stored in the liver as glycogen and released again into the
circulation (hepatic glucose production), when BG level drops too low between the
meals. This is the internal source of glucose. Inside a cell, with the help of oxygen
glucose is metabolized into water and carbon dioxide, producing energy [21, 22].
Insulin is the key hormone involved in the storage and controlled release of
chemical energy available from glucose in circulation. Insulin is synthesized in the cells of the Islets of Langerhans in the pancreas. It is carried to the liver, helps the
liver to take up glucose to store as glycogen. It acts as a catalyst, for glucose uptake in
muscles and periphery to produce energy. It has a second function also to turn off
the release of internal glucose into bloodstream by the liver and muscle at the time
of food intake. In diabetic patients, both these functions are absent; cells do not get
energy, but liver produces internal glucose resulting in an uncontrolled rise of BG
level [21, 22].

2.3. Modeling of a diabetic patient

The Diabetes Control and Complications Trial (DCCT) research [22, 23] proved
that intensive glucose control to maintain normal range of plasma glucose level (normoglycaemia) within 8190mg/dl helps to prevent later life complications like heart
attacks, strokes, amputations, renal failure, retinopathy and neuropathy. In modern intensive therapy, the diabetic patients of type-1 and in some cases of type-2 attempt to
lead normal life style by adjusting the insulin dose adaptively to the daily schedule of
meals and exercise. Implantable insulin dispenser systems are now being used for administering insulin at a controlled rate in close loop [2, 4, 9, 10, 1315, 24]. The glucose metabolism of a diabetic patient is a complex nonlinear process with a number of
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internal factors, which are not easily accessible for measurement. Only with accessible
information, like occasional BG measurements, information about food (carbohydrate) intake and physical exercise the system appears to be highly stochastic and the
quantity of interest, the BG concentration is difficult to model and predict.
2.3.1. Model of the physiological process. Different models of the diabetic patient have been described in several literatures [9, 10, 25, 26] to find the dynamics of
various preparations of insulin to regulate the glucose level. Parker et al. [9, 10] and
Lehmann et al. [25, 26] have made major research works on such models. With the
advent of implantable sensors and pumps [2, 8, 10, 24, 27, 28] closed loop regulation
of arterial glucose has become feasible [3, 912]. A flow-limited multivariable model
of the present glucose-insulin process with implanted insulin pump is shown in fig. 2.
This model assumes that the patient is completely lacking the endogenous insulin production and a single glucose pool represents the extra-cellular glucose. Glucose enters
the blood stream via both intestinal absorption and hepatic glucose production. The
stomach and intestine effects are lumped into the gut compartment. Glucose is used
up by two ways: (i) insulin independent utilization in central nervous system (CNS) or
brain and red blood cells (RBC) and (ii) insulin dependent utilization in the liver and
periphery. The periphery represents the combined effects of muscles and the adipose tissues. The physiological functions of the organs involved in glucose metabolism process and the anatomical basis of these functions have been discussed in detail
in literatures [25, 26]. The regulated output, the arterial glucose level is measured
and the control input is the infusion of fast acting insulin [4, 22] to the blood stream
by the implanted pump at an interval of 5 minutes. The sampling rate depends on the
device and sensor technology [6, 8, 27, 28]. The variables, meal to the gut compartment and exercise to the periphery are added to the model as the process disturbances.

Fig. 2. Compartmental model of glucose-insulin interaction with closed loop control.

2.3.2. Micro-insulin dispenser system. We consider a 5th order transfer function

for the micro-insulin dispenser as described by Cochin et al. [28]. It operates on variable pumping rate principle [10, 28]. The device of the size of a pacemaker consists of
an insulin storage capsule, a micro pump (electrostatic valve) with return valve, flu-

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idic accumulator and necessary electronic control as shown in the block diagram of
fig. 3. The insulin command is a reference current and the pump infuses insulin in to
the blood stream at the rate of few mU/min.
Pd
Iref

V
F
Y
Po +
1
1
Ke
K
v
+
Cs+1/ R
Ms2 + Ds + K
E S VALVE

Wp
1
I f s + R f s + 1 / C f (mU/min)
2

ELECTRO-MECHANICAL MOVEMENT

FLUID CIRCUIT

Fig. 3. Block diagram of micro-insulin dispenser

2.3.3. Linearization of the process model. The model of the diabetic patient has
been simulated by MATLAB/SIMULINK [29] using the nonlinear pharmacokinetic
and pharmacodynamic equations of glucose-insulin interaction process [25] and the
5th order dynamics of the insulin delivery device [1315, 28]. The multivariable nonlinear patient model with three inputs and one output is shown in the block diagram of
fig. 4.

Fig. 4. patient_model block showing the inputs and output.

The linear state-space model for the blocks of fig. 4 can be expressed as:
x& = Ax + Bu + Gw
(1)
y = Cx + Du
where, x is the state vector, u is the insulin command, w is the disturbance input vector comprising meal(w1) and exercise(w2) disturbances, y is the regulated glucose
level. A, B, G, C and D are the linear system matrices. Small signal linear approximation of the simulated nonlinear model around the reference plasma glucose level
81mg/dl and basal insulin dose 22.3mU/ml gives the following non-minimum phase
system matrices:
0 . 0001

A=
0

. 000016

. 00008

0 . 0003

0
0

. 0020
. 000007

0
. 0003

0
0

114 . 47
0

0
0

0
0

0
0
0

0
0
0

0
0
0

24 . 0
1
0

256 . 0
0
0

0
0
12 . 5

0
0
72 . 67

0
0

0
0

0
0

0
0

0
0

1
0

0
1

0 . 125

33 . 335

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0
0

0

0
B = 0 ;

0
1

0
0

0
1

0
G = 0

0
0

0
0

0 . 057143
0
0
0
0
0
0
0
0

C = [1

0 ]; D = [ 0 ]

3. LQG design for the glucose regulation problem

3.1. LQG control equations
We apply LQ optimization methods on the linear process model described in the
last section. Fig. 5 shows the detailed block diagram of the LQG control for the present problem showing the estimator and controller blocks separately, where reference
input is the desired plasma glucose level. The meal and exercise disturbances (w) and
the measurement noise (v) from the glucose sensor are random and Gaussian noises.

Fig. 5. Block diagram of LQG control for the glucose regulation problem.

3.1.1. Estimator and controller equations. With the state and output equations
of (1), the transfer function of the linear model of the physiological process from control input u to the regulated output y is given by:
(2)
G p ( s ) = C ( sI A) 1 B
The estimation of the states (x ) for the present process is obtained from the Kalman
filter using the nominal system matrices of the linear model as follows:
x& = Ax + Bu + K f ( r + y y ) = ( A BK c K f C ) x K f (r y )
(3)
y = Cx
where r is the reference plasma glucose level (say, 4.5 mmol/l or 81mg/dl). The optimal control law u = K c x is applied on the estimated states. Kf and Kc respectively
are the optimal filter gain and the controller gain expressed as:
(4)
K f = C T V 1 ,
and

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K c = R 1 B T .
is the positive definite (=T > 0) matrix solution of the Filter Algebraic Riccati Equation (FARE):
A + A T + GWG T C T V 1C = 0 .
(6)
is the positive semi-definite (=T 0) matrix solution of the Controller Algebraic Riccati Equation (CARE):
AT + A BR 1 B T + C T QC = 0 .
(7)
Q and R are the state-weighting and input-weighting matrices for the LQ optimization problem. W, V are the covariance matrices for the random noise processes
representing process and sensor noise respectively. The controller transfer function is:
(8)
Gc ( s ) = K c ( sI A + BK c + K f C ) 1 K f .
Let us consider the estimation error, ~
x = x x , then
(9)
x& = Ax + Bu = Ax BK x + BK ~
x

(5)

~
x& = Ax + Bu Ax Bu K f ( r + y Cx ) = ( A K f C ) ~
x +Kfr

(10)

Thus from separation principle [16], we can write,

BK c x 0
x& A BK c
x
=
+ r and y = [C 0] ~
(11)

~
~
&x 0
A K f C x K f

x
If ( A K C ) is stable, ~
x converges to zero.
f

3.1.2. Robustness aspect of the LQG controller. One of the problems with
LQG method is that it requires statistical information of the noise processes. In most
cases this information is not available or impractical to obtain. The LQG combination
can have arbitrarily poor stability margin, as there is always a difference between the
actual state and the observed states. The pass-band robustness properties are no longer
guaranteed with the introduction of state estimator in presence of noise. LQG open
loop transfer function does not satisfy the return difference inequality [18, 20]. For the
present problem, we obtain the loop gain at the output from equations (2) and (8) as:
(12)
G l ( s ) = G p ( s )G c ( s ) =
= C ( sI A) 1 BK c ( sI A + BK c + K f C ) 1 K f
To establish the output loop recovery we use the following notations
( s ) = ( sI A) 1
and
( s ) = ( sI A + K f C ) 1 .
Applying the matrix inversion lemma [19],
( A + BCD) 1 = A 1 A 1 B( DA 1 B + C 1 ) 1 DA 1 ,
the following loop transfer function is obtained:
Gl ( s ) = C ( s ) BK c ( ( s ) 1 + BK c ) 1 K f =
(13)
= C ( s ) BK c [ ( s ) ( s ) B( K c ( s ) B + I ) 1 K c ( s )]K f =
= C ( s ) BK c ( s )[ I ( BK c ( s ) + I ) 1 BK c ( s )]K f =
= C ( s ) BK c ( s )( BK c ( s ) + I ) 1 K f .
We consider the state-weighting matrix Q = Q0 + M and as tends to , the
CARE equation (7) becomes:

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(14)

A AT
Q
BR 1 B T
lim
+
+ 0 +M

= 0 .

= 0 and Kc can be obtained from the following two equations.

BR 1 BT
,
M=

M = Kc R .

As , lim
(15)
(16)

M
lim ( K c ) = lim


R

As

(17)

Choosing M = I, the open loop transfer function becomes

lim (G l ( s )) = lim C ( s ) B

( s )( B

( s ) + I ) 1 K f =
R

= lim C( s )
( s) 1 ( s) R B 1K f =

R

= C( s) K f
This result shows that with very large value of we can approach the return ratio
of the Kalman filter. The effect of loop transfer recovery (LTR) at output is thus
matching of the poles and zeros of the compensator as shown below:
The poles of Gc(s)| ,

the zeros of the system C(s)Kf.

The zeros of Gc(s)| ,

the zeros of the system C(s)B.

4. Glucose regulation using LQG/LTR

control of insulin delivery system
4.1. Study of patient dynamics
In the following sections, we will study the response of the glucose-insulin process with various control configurations for the meal disturbance OGTT (oral glucose
tolerance test) or glucose meal ingestion of 60 gm at t = 40000sec and a half-an-hour
exercise noise of 0.005 arbitrary unit at t = 90000sec along with additive Gaussian activity noise. The pure dynamics of the patient model is obtained from the study of
transient response of the uncontrolled process with a constant insulin infusion of 22.3
mU/min (supposed to be the basal dose) and a process noise profile just described.
The response of the uncontrolled process in fig. 6 shows a larger effect of meal disturbance compared to the exercise noise. For LQ design, thus maximum weightage is
given on the states responsible for the plasma glucose level. The weighting matrices
are therefore chosen as Q =1000*CTC and R =1. The glucose-insulin profile with full
state feedback LQ regulator (LQR) in fig. 7 shows a poor sensitivity of the controller.

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Fig. 6. Response of the uncontrolled process.

Fig. 7. Response of full state feedback LQ regulator

4.2. Disturbance model of the patient

Considering meal and exercise inputs as the process disturbances (w) and the
measurement noise (v) of glucose sensor all being random and Gaussian in nature, we
can develop the disturbance model with the respective noise intensities W and V.
4.2.1. Process noise. Correlation between the meal and exercise disturbance inputs is unlikely to exist. Hence W is considered diagonal. Considering larger noise intensity for the meal disturbance, we take the co-variance matrix for the process noise:
1000 0
(18)
W =
1
0
4.2.2. Sensor noise. Noise signals from the sensors are usually uncorrelated i.e. V
is also diagonal. Expected values of the rms noise (i) from the sensor are available
from the manufacturers specifications; V = diag(i2). Hence from the available data
of a single glucose sensor with 5% measurement noise (standard deviation=3.8 mg/dl
for the glucose sensor), we can take:
(19)
V = 0.0025 .

4.3. Response of LQG design

4.3.1. Continuous time design. Design of LQG controller with the continuous
time model is obtained from equations (4) to (7). We use the following noise constant
WC to solve the FARE equation (6). The plasma glucose response is shown in fig. 8.
(20)
WC = [G ][W ][G ]T .
4.3.2. Discrete time LQG control. The discrete time state-space model of the
present physiological system may be described as:
x(k + 1) = x(k ) + u (k ) + w w(k )
(21)
.
y (k ) = CD x(k ) + DD u (k ) + v(k )
For insulin infusion at a regular interval of 5min, the following discrete time system
matrices , , w, CD and DD are computed from the linear system matrices of equation (1) using a sampling interval of 300sec.

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0
3.33e 5 .0008 1.24e 7 1.55e 6 8.99e 6
.00011 1.59e 5 7.45e 5

0
.00028
0
0
0
0
0
0
0

0
0
.001983
0
.0021
.0503
7.89e 6 9.86e 5 .0005732

0
6.69e 6 .00035 2.99e 6 7.18e 5 1.11e 8 1.39e 7 8.08e 7
0

= 0
0
0
0
.00667
0
0
0
0

0
0
0
0
.00667
0
0
0

0
0
0
0
0
0
.00667
0
0

.00667
0
0
0
0
0
0
0

0
0
0
0
0
0
0
0
0
.00667

. 00052

. 482430

. 000053
w ] =
0

. 000029

. 059997

. 01388
299 . 83
0
0
0
0
0
0
0

17 . 141

;
0

Fig. 8. Glucose-insulin response of LQG

controller with continuous time model.

CD

. 003389
7 . 93 e 6

3 . 73 e 5

= 1 . 67 e 5 ;

. 0003998
6 . 18 e 8

7 . 73 e 7
4 .5e 6

D D = [0 ]

Fig. 9. Glucose-insulin response of discrete

time LQG controller with the patient model.

The predictor-corrector equations for one-step-ahead Kalman estimator with gain

Kf for the discrete-time model are:
x (k | k 1) = x (k 1 | k 1) + u (k 1)
(22)
x (k | k ) = x (k | k 1) + K f (k )( y (k ) CD x (k | k 1) )
For discrete time design, following noise constant, WD has been used to solve the
discrete FARE equation.
(23)
WD = wWwT .
The response for the plasma glucose level with discrete time LQG design is
shown in fig. 9. The discrete time design shows an improved glucose regulation.

4.4. Augmented system model

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Instead of random noise, we now consider a fixed dynamics for the meal (d1) and
exercise (d2) disturbance process, which are generally periodic within 24 hours. Thus
a pre-filter fed by white noise source may be considered to generate the colored noise
sequence for the disturbance inputs of fig. 1.
4.4.1. Continuous-time augmented system model. Let us consider xp the plant
state vector, d=[d1 d2]T the identified process disturbance vector and v the random
measurement noise with zero mean; then the state space equation of the plant can be
expressed as:
x& p = Ap x p + B pu + G p d
(24)
y = C p x p + Dpu + v
and the state-space disturbance model with disturbance states xd is given by:
x&d = Ad xd + Bd w
(25)
d = Cd xd + Dd w
where w is the random white noise sequence driving the disturbance model and the
subscript d denotes the states and matrices of the disturbance process. The augmented system combining the states of the plant and disturbance models is thus expressed as:
x&a = Aa xa + Bau + Ga w
(26)
y = Ca xa + Da u + v
where x a = [ x p x d ]T is the augmented state vector and the augmented system matrices
are:
(27)

A GpCd
G D
B
Aa = p
; Ba = p ; Ga = p d ; Ca =[Cp 0] and Da = Dp .

Ad
0
0
Bd

4.5. LQG/LTR controller design for drug delivery

Let us examine the frequency domain behavior and loop gain properties of the
model from the respective singular value plots of the estimator, the controller, the uncontrolled process, LQR and LQG controlled process as illustrated in fig. 10. The aim
of the LTR design is to recover the return difference of the Kalman estimator i.e., we
want to get back the initial plot of singular values of open loop transfer function of the
observed plant in a relatively large frequency band as found with the LQR design.
4.5.1. LTR design on continuous time model. We have computed the estimator
gain with continuous time model and in the second step we apply output loop recovery
(equation 17) and increase the factor . The Nyquist plots of the closed loop system
with varying between 1 and 10000 are shown in fig. 11.

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Fig. 10. The behavior of uncontrolled and

from controlled dynamics in frequency domain.

Fig. 11. Nyquist plots with varying

1 to 10000 with output loop recovery.

With LQG control on nominal plant model, it is observed that = 10000 allow
the maximum recovery of the plant estimator in a rather wide interval (until 1 rad/s)
for the process but with poor sensitivity of . This yields infinite gain margin but produces poor phase margin. The loop gain property of this output LTR is illustrated in
fig. 12. This results a large improvement in disturbance rejection as revealed in the
glucose response of fig. 13.

Fig. 12. Maximum loop recovery obtained

with the LTR design for =10000.

Fig. 13. Rejection of disturbances with

maximum loop recovery at output.

4.5.2. Loop recovery with augmented system. It is true that LTR scheme can be
applied to unstable plants without difficulty, since unstable poles are shifted by the
feedback into the left half plane if all zeros and poles have the negative real part.
However, perfect recovery cannot be obtained in non-minimum phase systems like the
present glucoseinsulin process. The recovery may be achievable at those frequencies
at which the plant response is very close to that of a minimal phase plant i.e. it permits
adequate loop recovery in the frequency band of interest, as long as the non-minimum
phase zeros are outside this band [18]. The periodic meal and exercise disturbances
within 24 hours may be obtained from a pre-filter with its poles close to j*= /12
rad/hour. A first order low pass filter with the disturbance inputs results:
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(28)

. 00029
Ad =
0

0 .1
0
for each
d = F ( p)w =
w.

p + 0.00029
. 00029

from equation (25). The known results for the standard (non-frequency shaped) loop
recovery have been applied to the augmented plant model with colored disturbances
and the singular value plots show that the loop recovery takes place in a lowfrequency band and the roll-off rate characteristics of the original LQ design are preserved as is revealed from fig. 14. The glucose response with augmented model is
shown in fig. 15.

Fig. 14. Loop Recovery of the augmented

system model with colored noise input

Fig. 15. Time domain response with the

continuous-time augmented system.

4.5.3. Loop recovery with discrete-time design. By increasing noise variances

loop recovery of the non-minimum phase process may be established [18]. With discrete-time LQG control, the noise constant computed from continuous time model, WC
of equation (20) for solving the discrete FARE equation produces better glucose-meal
rejection compared to that using WD of equation (23). The response is shown in fig.
16. Discrete LQG design with WC and Q computed from the continuous time model
effectively increases the noise variances, and thus ideal loop recovery for the nonminimum phase system is established. A guaranteed stability margin is obtained by
this discrete time LQG/LTR design as shown in the singular value (SV) plots of fig.
17.

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Fig. 16. Response of the proposed discrete

time LQG design shows large noise rejection.

Fig. 17. The SV plot of discrete LQG/LTR

design shows maximum loop recovery.

A comparative study of various control algorithms like the model predictive control with state estimation (MPC/SE), nonlinear quadratic dynamic matrix control with
state estimation (NLQDMC/SE) algorithms from literature [9] and the LQG/LTR control algorithms discussed here has been made. The meal disturbance rejections in
terms of the overshoot and undershoot about the reference plasma glucose level and
the settling time measured from the instant of meal ingestion with these controllers are
shown in table 1. Clearly the utilization of LQG/LTR control provides significant improvement.
Table 1. Comparative study of meal disturbance rejection reflected in the plasma glucose level.
Controller

From literature [9]

LQG control
LQG with Loop Transfer Recovery
NLQD (cont.-time) (discr.-time) (Output LTR) (freq-shaping) (discr.-time LTR)
Types ! MPC/SE
MC/SE [ref. fig. 8] [ref. fig. 9] [ref. fig. 13] [ref. fig. 15] [ref. fig. 17]
Nil
Nil
5%
5%
5%
5%
5%
Meas. noise
50
50
60
60
60
60
60
OGTT (gm)
Overshoot
4.0
2.0
6.5
2.9
2.1
2.5
1.3
(mg/dl)

Undershoot
(mg/dl)

Settling
time (min)

4.4

3.6

0.3

1.0

0.8

0.2

0.4

204

216

217

208

200

221

183

5. Conclusion
The design methodology of LQG/LTR controllers for the BG regulation in diabetic patient through implanted insulin dispensing device has been discussed. The
nonlinear model of the patient and the device has been developed from literature data
and a 9th order linear state-space model derived around the operating point of 81mg/dl
plasma glucose level and a 22.3mU/min basal dose of insulin. The various
LQG/LTR designs with more accurate patient model for continuous insulin infusion
yield improved meal and exercise disturbance rejection compared to MPC/SE and

III SICPRO 04 28-30 2004 .

Proceedings of the III International conference System Identification and Control Problems SICPRO 04 Moscow 28-30 January 2004

1327
NLQDMC/SE schemes from literature. The output LTR has very poor sensitivity for
the present non-minimum phase system. The frequency shaped loop recovery applied
on the augmented system produces robust performances in wide frequency band of the
noise process. The discrete time design provides full loop recovery for the present
non-minimum phase system.
Advancement in MEMS technology and mechatronics design [30] has helped the
ideal miniaturization of drug delivery devices with a combination of good mechanical
design and intelligent and precision control strategies. Software like 20-sim may be
used to find proper parameters of the device model and interfaced with MATLAB routine to compute LQG/LTR controller, and the results can then be imported in to 20sim to determine overall parameters of the integrated system. Over and above, the
digital nature of control algorithms allows potential implementation on application
specific integrated circuits (ASIC) with long-term in vivo sensors.

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Proceedings of the III International conference System Identification and Control Problems SICPRO 04 Moscow 28-30 January 2004