Nonlinear Control of Blood Glucose Level in

Type 1 Diabetes Patients

Nonlinear Control of Blood Glucose Level in
Type 1 Diabetes Patients

Thesis submitted for the partial fulfillment of

Degree of Master of Science (MS) in Electronic Engineering

By
Sayyar Ahmad

Supervised by
Dr. Nisar Ahmed

Faculty of Electrical Engineering

GIK Institute of Engineering Sciences and Technology,
Topi, Swabi, KPK, Pakistan
 IN THE NAME OF ALLAH,
THE MOST MERCIFUL, THE MOST COMPASSIONATE
 Certificate of Approval

Nonlinear Control of Blood Glucose Level in Type 1 Diabetes Patients

Certified that the research work presented in this thesis, entitled “Nonlinear Control of
Blood Glucose Level in Type 1 Diabetes Patients” was conducted by Mr. Sayyar Ahmad
under the supervision of Dr. Nisar Ahmed and Dr. Nasim Ullah.

Dr. Nisar Ahmed (Supervisor), Dr. Nasim Ullah (Co-Supervisor),

Professor Dean, Associate Professor,
Faculty of Electrical Engineering Faculty of Electrical Engineering.
GIK Institute of Engineering Sciences CECOS University of IT and
and Technology Topi, Swabi Emerging Sciences, Peshawar

i
 Dedication

To my beloved parents, brothers, sisters, wife and daughter

ii
 Acknowledgment

First of all, I would like to express my deepest gratitude to Almighty Allah, the Creator, the
most Merciful and the Beneficent, for His countless blessings and to enable me achieve this goal.
I also offer my praises to Holy Prophet MUHAMMAD (S.A.W.) and his companions who laid the
foundations of Islamic civilization and paved the way for social, moral, economic, and cultural
revolution.
I am highly indebted to my advisor Dr. Nisar Ahmed and co-advisor Dr. Nasimullah. Working
with them has been a wonderful experience from many aspects. First, their belief in my abilities
has kindled my interest in research. Second, their encouragement to come up with my own original
ideas has helped me appreciate the value of formulating meaningful research problems and had a
profound effect in shaping my vision for future research. I thank them for their laudable teaching
and guiding me in accomplishing this work.
I would like to acknowledge GIK Institute for sponsoring my MS studies and for providing me
such a memorable environment. I am also grateful to the following former or current staff at Faculty
of Electrical Engineering,GIK Institute for their various forms of support during my graduate study
Dr. Husnul Maab, Dr. Adnan Noor, Dr. Ziaul Haq Abbas, Dr. Khasan Karimov, Ali Ghais, Mazhar
Javed, Mehran Bashir, Zaiwar Ali, Ikram Ullah, Iftikhar Ali Khan and Muhammad Arshad.
To all my friends, thank you for your understanding and encouragement in my many many
moment of crisis. Your friendship makes my life a wonderful experience. I would like to ac-
knowledge Attiq Ahmed, Ejaz Khan, Mussawer Pervez, Muhammad Tariq, Umer Farooq, Imran,
Ammar Ahmed, Salman Khan, Nihad Ali, Waqar Alam, Attiq ur Rehman, Muhammad Ilyas, Awais,
Muhammad Adil, Obaid, Shaukat, and Shakeel.
Most importantly, none of this would have been possible without the love and patience of my
family. My immediate family to whom this dissertation is dedicated to, has been a constant source
of love, concern, support and strength all these years. I would like to express my heart-felt gratitude
to my family. My extended family has aided and encouraged me throughout this endeavor. I warmly
appreciate the generosity and understanding of all of them.
Sayyar Ahmad
April, 2017

iii
iv
 Declaration

I declare that this is my own work and has not been submitted in any form for another degree
or diploma at any university or other institution for tertiary education. Information derived from
published or unpublished work of others has been acknowledged in the text and a list of references
is provided at the end of this dissertation.

Sayyar Ahmad
April, 2017

v
 Abstract

Diabetes mellitus is one of the most common diseases in the world. Specifically, type 1 diabetes
mellitus in which pancreas of patient does not produce insulin resulting in high concentration of
glucose in blood plasma for longer periods of time. High concentration of glucose can cause many
complications and may lead to death. For this purpose strict control of blood glucose concentration
is required in type 1 diabetes patients. In this research work nonlinear closed loop control algorithms
have been investigated for blood glucose regulation in type 1 diabetes patients, which can be used
in automatic insulin pumps, referred to as artificial pancreas in literature. Bergman’s minimal model
is considered for studying dynamical behavior of glucose and insulin inside human body.As slid-
ing mode control (SMC) is known for its robustness against disturbances and mismatches, therefore
three nonlinear control strategies based on SMC have been developed and analyzed, namely Classi-
cal Sliding Mode Control (CSMC), Super Twisting Sliding Mode Control (STSMC) and Backstep-
ping Integral Sliding Mode Control (BISMC). CSMC based controller shows chattering, which may
be dangerous in practical actuation of controller. In order, to cope with the problem of chattering
STSMC algorithm is developed. For improving the transient response of controller a novel BISMC
is introduced and developed showing satisfactory results. The advantages of backstepping and in-
tegral SMC are combined for achieving the desired performance. Problem of hypoglycemia related
to previous nonlinear control techniques is also removed by using proposed controller. Three cases
have been considered for analysis of the SMC based controllers. Firstly the controllers are subjected
to patient having hyperglycemia whose blood glucose was high. Secondly, controllers are analyzed
for patients having hyperglycemia and meal disturbance. Finally, controllers are studied for patients
subjected to three meal intakes (as disturbances) corresponding to break-fast, lunch and dinner. It
is shown that proposed BISMC based controller shows best performance and successfully stabilize
the glucose level of patient for above mentioned three cases. A comparison of CSMC, STSMC and
BISMC can be found in results. Meal disturbance to diabetes patient is also explicitly given in sim-
ulation results. Simulation results are provided to show superiority and advantages of the proposed
controller such as robustness to external disturbances, no chattering, less control effort and accurate
output tracking, thus proposed controller can be considered a suitable choice for designing automatic
insulin pumps for type 1 diabetes patients.

vi
Contents

Dedication i

Acknowledgment ii

Declaration iv

Abstract v

List of Figures x

List of Tables xii

Abbreviations xiii

1 Introduction 1
1.1 Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Type 1 DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1.2 Type 2 DM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1.3 Pancreas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1.3.1 Alpha Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1.3.2 Beta Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1.4 Regulation of Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2 Control Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.1 Linear Control Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.2.2 Nonlinear Control Review . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Problem Statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.4 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.5 Thesis Outline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

2 Modeling of Glucose-Insulin Dynamics 6

2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
2.2 Bergman’s Minimal Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

vii
 2.2.1 Glucose Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2.2.2 Block Diagram for Glucose Dynamics . . . . . . . . . . . . . . . . . . . . 10
2.2.3 Insulin Dynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2.2.4 Block Diagram for Insulin Dynamics . . . . . . . . . . . . . . . . . . . . 11
2.3 Complete Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
2.3.1 Block Diagram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

3 Sliding Mode Control for Blood Glucose Regulation in Diabetes Patients 13

3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3.2 Sliding Mode Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3.2.1 Reaching Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.2.2 Sliding Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.3 SMC Based Controller Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
3.3.1 Sliding Manifold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.3.2 Equivalent Control Law . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
3.3.3 Discontinuous Control Law . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.3.4 Simulation Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3.3.4.1 Regulation of Glucose during Hyperglycemia . . . . . . . . . . 17
3.3.4.2 Regulation of Glucose during Hyperglycemia and Meal Distur-
bance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.3.4.3 Regulation of Glucose in Presence of 3 Meal Disturbance . . . . 22
3.3.5 Drawbacks of Classical SMC . . . . . . . . . . . . . . . . . . . . . . . . . 23
3.4 Super Twisting SMC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.4.1 STSMC Based Controller Design . . . . . . . . . . . . . . . . . . . . . . 24
3.4.1.1 Sliding Manifold . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.4.1.2 Equivalent Control Law . . . . . . . . . . . . . . . . . . . . . . 24
3.4.1.3 Switching Control Law . . . . . . . . . . . . . . . . . . . . . . 24
3.4.2 Simulation Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
3.4.2.1 Regulation of Glucose during Hyperglycemia . . . . . . . . . . 25
3.4.2.2 Regulation of Glucose during Hyperglycemia and Meal Distur-
bance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.4.2.3 Regulation of Glucose in Presence of 3 Meal Disturbance . . . . 29

4 Backstepping Integral Sliding Mode Control for Blood Glucose Regulation in Dia-
betes Patients 32
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.2 Backstepping Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

viii
 4.3 Backstepping Integral Sliding Mode Control . . . . . . . . . . . . . . . . . . . . . 33
4.3.1 Derivation of Control Law . . . . . . . . . . . . . . . . . . . . . . . . . . 33
4.3.2 Simulation Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
4.3.2.1 Regulation of Glucose during Hyperglycemia . . . . . . . . . . 34
4.3.2.2 Regulation of Glucose during Hyperglycemia and Meal Distur-
bance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
4.3.2.3 Regulation of Glucose in Presence of 3 Meal Disturbances . . . 37
4.4 Comparative Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
4.4.0.1 Regulation of Glucose during Hyperglycemia . . . . . . . . . . 39
4.4.0.2 Regulation of Glucose during Hyperglycemia and Meal Distur-
bance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
4.4.0.3 Regulation of Glucose in Presence of 3 Meal Disturbance . . . . 42

5 Conclusion and Future Work 45

5.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
5.2 Future Work . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

References 47

ix
List of Figures

1.1 Pancreas [6] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

2.1 Dynamics of Glucose Concentration in Blood Plasma . . . . . . . . . . . . . . . . 10

2.2 Dynamics of Insulin Concentration in Blood Plasma . . . . . . . . . . . . . . . . . 11
2.3 Block diagram of Bergman’s minimal model . . . . . . . . . . . . . . . . . . . . . 12

3.1 Reaching and Sliding Phase in SMC . . . . . . . . . . . . . . . . . . . . . . . . . . 14

3.2 Glucose concentration during hyperglycemia using SMC . . . . . . . . . . . . . . . 17
3.3 Output error during hyperglycemia using SMC . . . . . . . . . . . . . . . . . . . . 18
3.4 Insulin concentration during hyperglycemia using SMC . . . . . . . . . . . . . . . 18
3.5 Control input during hyperglycemia using SMC . . . . . . . . . . . . . . . . . . . 19
3.6 Meal disturbance used for simulation . . . . . . . . . . . . . . . . . . . . . . . . . 19
3.7 Glucose concentration in presence of meal disturbance using SMC . . . . . . . . . 20
3.8 Output error during meal disturbance using SMC . . . . . . . . . . . . . . . . . . . 20
3.9 Insulin concentration in presence of meal disturbance using SMC . . . . . . . . . . 21
3.10 Control input in presence of meal disturbance using SMC . . . . . . . . . . . . . . 21
3.11 Three meal disturbance used for simulation . . . . . . . . . . . . . . . . . . . . . . 22
3.12 Glucose concentration in presence of 3 meal disturbance using SMC . . . . . . . . 22
3.13 Insulin concentration in presence of 3 meal disturbance using SMC . . . . . . . . . 23
3.14 Control input in presence of 3 meal disturbance using SMC . . . . . . . . . . . . . 23
3.15 Glucose concentration during hyperglycemia using STSMC . . . . . . . . . . . . . 26
3.16 Output error during hyperglycemia using STSMC . . . . . . . . . . . . . . . . . . 26
3.17 Insulin concentration during hyperglycemia using STSMC . . . . . . . . . . . . . . 27
3.18 Control input during hyperglycemia using STSMC . . . . . . . . . . . . . . . . . . 27
3.19 Glucose concentration in presence of meal disturbance using STSMC . . . . . . . . 28
3.20 Output error during meal disturbance using STSMC . . . . . . . . . . . . . . . . . 28
3.21 Insulin concentration in presence of meal disturbance using STSMC . . . . . . . . . 29
3.22 Control input in presence of meal disturbance using STSMC . . . . . . . . . . . . . 29
3.23 Glucose concentration in presence of 3 meal disturbance using STSMC . . . . . . . 30
3.24 Output Error in presence of 3 meal disturbance using STSMC . . . . . . . . . . . . 30

x
3.25 Insulin concentration in presence of 3 meal disturbance using STSMC . . . . . . . . 31
3.26 Control input in presence of 3 meal disturbance using STSMC . . . . . . . . . . . . 31

4.1 Glucose concentration during hyperglycemia using BISMC . . . . . . . . . . . . . 35

4.2 Insulin concentration during hyperglycemia using BISMC . . . . . . . . . . . . . . 35
4.3 Control input during hyperglycemia using BISMC . . . . . . . . . . . . . . . . . . 36
4.4 Glucose concentration in presence of meal disturbance using BISMC . . . . . . . . 36
4.5 Insulin concentration in presence of meal disturbance using BISMC . . . . . . . . . 37
4.6 Control input in presence of meal disturbance using BISMC . . . . . . . . . . . . . 37
4.7 Glucose concentration in presence of 3 meal disturbance using BISMC . . . . . . . 38
4.8 Insulin concentration in presence of 3 meal disturbance using BISMC . . . . . . . . 38
4.9 Control input in presence of 3 meal disturbance using BISMC . . . . . . . . . . . . 39
4.10 Comparison of glucose concentration during hyperglycemia . . . . . . . . . . . . . 40
4.11 Comparison of insulin concentration during hyperglycemia . . . . . . . . . . . . . 40
4.12 Comparison of control inputs during hyperglycemia . . . . . . . . . . . . . . . . . 41
4.13 Comparison of glucose concentration in presence of meal disturbance . . . . . . . . 41
4.14 Comparison of insulin concentration in presence of meal disturbance . . . . . . . . 42
4.15 Comparison of control inputs in presence of meal disturbance . . . . . . . . . . . . 42
4.16 Comparison of glucose concentration in presence of 3 meal disturbance . . . . . . . 43
4.17 Comparison of insulin concentration in presence of 3 meal disturbance . . . . . . . 43
4.18 Comparison of control inputs in presence of 3 meal disturbance . . . . . . . . . . . 44

xi
List of Tables

2.1 PARAMETERS USED IN GLUCOSE DYNAMICS DERIVATION . . . . . . . . . . 9

2.2 D ESCRIPTION OF REPLACED PARAMETERS USED IN DERIVATION . . . . . 9
2.3 PARAMETERS USED IN INSULIN KINETICS DERIVATION . . . . . . . . . . . 11

3.1 VALUES OF PARAMETERS USED FOR S IMULATION IN SMC A LGORITHM 17

3.2 VALUES OF PARAMETERS USED FOR S IMULATION IN STSMC A LGO -
RITHM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

4.1 VALUES OF PARAMETERS USED FOR S IMULATION IN BISMC A LGORITHM 34

xii
 Abbreviations

BCS Biomedical Control Systems

DM Diabetes Mellitus
WHO World Health Organization
IDF International Diabetes Federation
ADA American Diabetes Association
PID Proportional Integral Derivative
IVGTT Intravenous Gluocse Tolerance Test
SMC Sliding Mode Control
STSMC Super Twisting Sliding Mode Control
BISMC Backstepping Integral Sliding Mode Control
BC Backstepping Control

xiii
Chapter 1

Introduction

Control systems design has gain a tremendous attention in tackling the challenging control problems
in biomedical control systems (BCS). BCS in nature shows nonlinear behavior, for attaining accu-
rate control performance nonlinear control is the appropriate option in this scenario. Blood glucose
regulation is one of the most common and important problems in BCS. Abnormal behavior of blood
glucose levels causing different long term and lethal diseases is distinguished by a disease called
Diabetes Mellitus. Diabetes mellitus (DM) is a metabolic disease, which is rapidly increasing all
around the world. According to world health organization (WHO), diabetes victims are increased
from 108 million (1980) to 422 million (2014) [1]. Statistical analysis done by WHO reflect that di-
abetes would be number seven leading cause of death in 2030 [2]. A report released by International
Diabetes Federation (IDF) states if no action is taken against diabetes, approximately there will be
642 million diabetes patients in 2040, which is an increase of about 50 percent [3].

1.1 Diabetes Mellitus

Diabetes Mellitus is a collection of metabolic diseases distinguished by elevated blood glucose levels
due to disorder in insulin secretion, insulin action or both of them.Intense hyperglycemia of DM
results in complications, long-term diseases, failure of several organs like kidneys, nerves, heart,
eyes etc [4]. The normal level of glucose in blood plasma appears in a short range of 70 -130 mg/dL
during fasting condition and temporarily above 140 mg/dL prior to short time after meals as given by
American Diabetes Association (ADA) [5]. However, the level of glucose in human blood plasma
fluctuates throughout the day but stays within normal range. Hormones responsible for homeostasis
of glucose level in human are secreted by pancreas named Insulin and Glucagon. Whenever, glucose
level exceeds normal range, Insulin is secreted by beta cells to lower the glucose level to basal value
and Glucagon works in the reverse order thus achieving basal glucose level in normal subject.

1
Chapter 1 Introduction

1.1.1 Type 1 DM

Type 1 DM is a type of DM disease also known as insulin-dependent DM. In this type of DM the
immune system of human attacks its own pancreas and destroy the cells responsible for secretion of
insulin thus destroying the regulation of blood glucose levels at normal value.

1.1.2 Type 2 DM

It is the most common DM disease. In type 2 DM body of patient shows resistance to the secretion
of insulin by pancreas due to which not sufficient amount of insulin is secreted in order to regulate
the blood glucose level at normal value thus leading to hyperglycemia.

1.1.3 Pancreas

Pancreas is an endocrine organ located in abdominal cavity, playing vital role in homeostasis of
blood glucose level. Hormones responsible for regulation of glucose levels are secreted by pancreas
namely insulin and glucagon.

Figure 1.1: Pancreas [6]

1.1.3.1 Alpha Cells

The cells responsible for secretion of Glucagon are called alpha cells. They are located in islet of
langerhans within pancreas.

2
Chapter 1 Introduction

1.1.3.2 Beta Cells

The cells responsible for secretion of Insulin are called beta cells. They are located in islet of
langerhans within pancreas.

1.1.4 Regulation of Glucose

Glucose is an important source of energy for body cells, reaching cells through blood stream. In hu-
mans the glucose-insulin regulation system works under stiff homeostatic control condition. When-
ever glucose level in blood plasma exceeds normal value, insulin is secreted for regulation whereas
low levels of glucose in blood plasma are compensated by secretion of glucagon.

1.2 Control Literature Review

Due to lack of Insulin the blood glucose of patient remains dangerously high for long periods of
time. Untreated hyperglycaemia can result in long-term diseases such as cardiovascular diseases,
damaging nerves, damaging kidneys, damaging retina leading to blindness, bone and joints diseases,
skin diseases etc. Similarly very low blood glucose levels can also result in many diseases like
unconsciousness and coma which can be mortal [7]. Due to above mentioned complications caused
by abnormal blood glucose levels in diabetes mellitus patients accurate and precise control of blood
glucose concentration is extremely important. Therefore tight control of blood glucose in diabetes
patients remained an exciting area of research over last four decades.

1.2.1 Linear Control Review

The linear control algorithms developed for blood glucose regulation in DM patients are discussed
in this section. Among linear control strategies the Proportional Integral Derivative (PIDs) based
controllers i.e. Expert PID control [8], Robust PID control [9], Digital PID control [10], Genetic al-
gorithm based PID control [11] and switching based PID control startegy [12] were proposed. Other
linear controllers deployed are glucose control based on feed forward-feedback strategy [13], con-
trol algorithm based on pole placement technique [14], controller based on discrete model prediction
algorithm [15], and H∞ based robust control design [16].

1.2.2 Nonlinear Control Review

Besides linear control algorithms researchers also show keen interest in designing nonlinear con-
trollers for blood glucose regulation in diabetes patients to achieve the required performance.As
blood-glucose regulation is a nonlinear phenomenon in nature, thus nonlinear control can provide
better performance as compared to linear controllers based on linearized models. Some of nonlinear

3
Chapter 1 Introduction

controllers proposed are nonlinear robust controller based on model predictive algorithm [17], Con-
trol based on fuzzy logic [18], high order sliding mode control [19], adaptive gain high order sliding
mode control using fuzzy logic [20], recurrent based neural network control [21], sliding mode con-
troller based on backstepping technique [22], Fractional order PID controller [23], and fractional
sliding mode controller with adaptive gains [24].

1.3 Problem Statement

Due to lack of Insulin the blood glucose of patient remains dangerously high for long periods of
time. Untreated hyperglycaemia can result in long-term diseases such as cardiovascular diseases,
damaging nerves, damaging kidneys, damaging retina leading to blindness, bone and joints diseases,
skin diseases etc. Similarly very low blood glucose levels can also result in many diseases like
failure of consciousness i.e. coma which can be mortal [25]. Because of mentioned complications it
is necessary to regulate blood glucose level of diabetes patients. Blood glucose of human is effected
by many factors like meal, exercise, stress, fasting, sports activities etc. Controller designed must be
robust to such factors for tight control of blood glucose concentration.

1.4 Objectives
Designing a controller for tight control of blood glucose regulation in DM patients is a challenging
task. The control objectives are listed below:

• Transient response of the controller must be reasonable

• Controller must be insensitive to external disturbances like meals etc

• Controller should be robust against parameters variations

• Control action cannot be negative

1.5 Thesis Outline

Chapter 1 briefly introduces the research problem taken into consideration in this thesis.
Chapter 2 explains the modeling of glucose-insulin dynamics in human body. Bergman’s minimal
model is introduced and briefly derived.
Chapter 3 explains sliding model control design for blood glucose regulation in diabetes patients.
Controller is derived and simulation results are given. Super twisting sliding mode control algorithm
is also introduced and its advantages are shown in simulation results.

4
Chapter 1 Introduction

Chapter 4 introduces backstepping integral sliding mode control strategy for blood glucose reg-
ulation in type 1 diabetes patients. The performance of proposed controller is validated by including
simulation results. MATLAB software is used for simulation purposes.
Chapter 5 concludes the dissertation with a summary of findings and highlights future research
challenges.

5
Chapter 2

Modeling of Glucose-Insulin
Dynamics

2.1 Introduction
In order to design a model based controller mathematical modelling of the biomedical system de-
scribing the dynamics of insulin and glucose is necessary [26]. A lot of research is also carried
out on modelling of insulin-glucose dynamics inside human body. Researchers have proposed dif-
ferent models including linear models developed by Bolie 1961 and Ackerman et al 1965 [27,28].
Mentioned linear models are so simple with two states. Regarding nonlinear behaviour of glucose-
insulin dynamics physiological models developed are Tiran et al 1979, Sorensen 1985, Hovorka et
al 2004 and Dalla Man et al 2007 [29-31].Compartmental models derived for glucose-insulin dy-
namics consist of Bergman et al 1981, Cobelli et al 1982, Cobelli and Mari 1983 and Lehmann 1992
[32,33]. Among models of glucose-insulin dynamics discussed above Bergman’s minimal model
have been chosen for simulation study of the controller. Linear models stated are too simple and
cannot tackle challenges for appropriate control. Physiological models are very complex, consist-
ing of many state variables and parameters, making designing of a controller difficult and tedious.
While minimal model is one of the best pioneer models and consists of least parameters necessary.
Moreover, minimal model relates the main states in question i.e. glucose and insulin concentrations
[34].

2.2 Bergman’s Minimal Model

Complete Modeling of processes in human body requires complex mathematics to explain the actual
natural process. But in many scenarios the aim of modeling is to explain the natural process in a

6
Chapter 2 Modeling of Glucose-Insulin Dynamics

clear and simple way. Minimal models consist of least parameters and set of equations necessary
for explaining the process. One such model for explaining the blood glucose-insulin kinetics in man
was proposed by Richard N. Bergman in 1980. This minimal model is one of the pioneers and well-
known model of glucose-insulin regulatory system in man. In minimal model the body is considered
as a compartment composed of basal values of insulin and glucose concentrations therefore; also
known as one compartment model. Minimal model consists of two parts. One explaining dynamics
of glucose, how concentration of glucose is affected by concentration of insulin in blood. Second
part is given to explain the effect of glucose concentration on insulin concentration in blood. The
derivation of glucose-insulin dynamics used in minimal model is based on Intravenous Glucose
Tolerance Test (IVGTT).

2.2.1 Glucose Dynamics

Modeling of glucose dynamics is based on IVGTT, behavior of glucose concentration to insulin in

blood. There are two parts in model of glucose dynamics. First part shows production and consump-
tion of glucose. Second part explains effect of active insulin present in remote compartments. Two
differential equations are used for mathematical description of two parts describing glucose kinetics
which are given below:
dGb (t)
= −(p1 + Xb (t))Gb (t) + p1 Gb (2.1)
dt
dXb (t)
= −p2 Xb (t) + p3 (Ib (t) − Ib ) (2.2)
dt
In order to understand these equations derivation will be very helpful in this regard. Derivation of
glucose dynamics model is based on mass balance rule and description given by Steil et al [35]. In
this model the body is considered as a compartment having certain volume VGb . The in and out
flow of glucose results in basal concentration of glucose Gb . Using mass balance rule the process
inside compartment can be described mathematically. The concentration of glucose accumulated in
compartmen can be written as:

accumulated = VGb .Gb (to + ∆t) − VGb .Gb (to )

There exist two kinds of masses flowing out of compartment, i.e consumption of glucose by liver and
periphery. There exists one in going mass, i.e production of glucose by liver. This in and out flow
of glucose give rise to a basal concentration of glucose, determined by threshold Gb . According to
Steil et al. [35], basal concentration is given by difference of consumption and production of glucose
independent of glucose and insulin uptginind , prodginind respectively. When glucose level exceeds
Gb , glucose level is decreased by consumption of glucose by liver upli and periphery tissues upph .
When glucose level is below Gb liver produces glucose until Gb is reached. Steil et al, referred this
balance as Net Hepatic Glucose Balance (NHGB) [35]. NHGB and upph are given by:

7
Chapter 2 Modeling of Glucose-Insulin Dynamics

uptph = (QGb1 .Gb (t).∆t + Gb (t).k.ωb1 .Xb (t).∆t) + uptginind

N HGB = prodginind − (QGb2 .Gb (t).∆t + Gb (t).k.ωb2 .Xb (t).∆t)

For changing L to dl k is used; a constant and is set to 1. Now using mass balance rule:

accumulated = in − out + produced − used

accumulated = N HGB − upph
VGb .Gb (to + ∆t) − VGb .Gb (to ) = prodginind − (QGb2 .Gb (t).∆t + Gb (t).k.ωb2 .Xb (t).∆t) −
(QGb1 .Gb (t).∆t + Gb (t).k.ωb1 .Xb (t).∆t) − uptginind

According to Steil et al, [35].

prodginind − uptginind = QGb1 .Gb .∆t + QGb2 .Gb .∆t

Dividing both sides by ∆t and VGb now we have:

Gb (to + ∆t)
=
∆t
QGb1 QGb2 QGb1 ωb1 QGb2 ωb2
Gb + Gb − ( Gb (t) + Gb (t)Xb (t) + Gb (t) + Gb (t)Xb (t))
VGb VGb VGb VGb VGb VGb
QGb1 ωb1 QGb2 ωb2
By replacing = k1 , = k4 , = k5 , = k6 and applying the limit ∆t → 0 the
VGb VGb VGb VGb
following differential equation is derived:

dGb (t)
= k1 Gb + k5 Gb − (k1 Gb (t) + k4 Xb (t)Gb (t)) − (k5 Gb (t) + k6 Xb (t)Gb (t)) (2.3)
dt

Differential equation derived above doesn’t show dynamics of active insulin present in remote com-
partments. Mathematical expression can be derived for dynamics of active insulin using mass bal-
ance rule as follows:

accumulated = Vxb .Xb (to + ∆t) − Vxb .Xb (to )

Whenever concentration of insulin in blood plasma Ib (t) is above the basal value Ib , insulin starts
flowing into remote compartment. If concentration goes below the basal value, insulin flows out of
the remote compartment, thus maintaining balance referred to as balins . Other outgoing mass from
remote compartment is proportional to the level of active insulin and is referred to as Xclr . Now
using mass balance theory we have:

accumulated = in − out + produced − used

accumulated = balins − Xclr
Vxb .Xb (to + ∆t) − Vxb .Xb (to ) = (QXb1 .(Ib (t) − Ib )∆t) − QXb2 .Xb (t)∆t

Dividing both sides by ∆t and Vxb and applying the limit ∆t → 0 the following differential equation
is derived:

8
Chapter 2 Modeling of Glucose-Insulin Dynamics

dXb (t) QXb2 QXb1

=− Xb (t) + (Ib (t) − Ib )
dt Vxb Vxb
QXb1 QXb2
By replacing = k2 and = k3 we get the following differential equation:
Vxb Vxb
dX b (t)
= −k3 Xb (t) + k2 (Ib (t) − Ib ) (2.4)
dt

Now by letting p1 = k1 + k5 , p2 = k3 and p3 = (k4 + k6 ) we get the model equations given in (2.1)
and (2.2).The block diagram of glucose dynamics given in minimal model is given below:

Table 2.1: PARAMETERS USED IN GLUCOSE DYNAMICS DERIVATION

Parameters Description Unit
Gb (t) Glucose concentration in blood mg/dL
Gb Basal value of Gb (t) mg/dL
Xb (t) Affect of active insulin 1/min
Ib (t) Insulin concentration in blood mU/L
Ib Basal value of Ib (t) mU/L
VGb Glucose compartment volume dL
VXb Volume of remote compartment L
QGb1 Flow of glucose dL/min
QGb2 Flow of glucose dL/min
QXb1 Flow of insulin L/min
QXb2 Flow of insulin L/min
ωb1 Effect factor dl2 /(min.mU )
ωb2 Effect factor dl2 /(min.mU )

Table 2.2: D ESCRIPTION OF REPLACED PARAMETERS USED IN DERIVATION

Parameters Description Unit
k1 Ability of glucose consumption by periphery 1/min
k2 Transport rate of insulin to remote compartment 1/min
k3 Clearance rate of active insulin 1/min
k4 Effect of active insulin on consumption by periphery L/(min.mU)
k5 Ability of glucose to change NHGB 1/min
k6 Effect of active insulin on NHGB L/(min.mU)

9
Chapter 2 Modeling of Glucose-Insulin Dynamics

2.2.2 Block Diagram for Glucose Dynamics

Figure 2.1: Dynamics of Glucose Concentration in Blood Plasma

2.2.3 Insulin Dynamics

Dynamics of insulin in body is described in minimal model by the following differential equation:

dI b (t)
= −n(Ib (t) − Ib ) + γ[Gb (t) − h]+ t (2.5)
dt

Derivation of insulin kinetics is also based on rule of mass balance like glucose kinetics. Assump-
tions used for derivation are described by Gaetano et al, [36]. Accumulated mass of insulin is
actually the difference between final and initial mass which is given by:

accumulated = VIb .Ib (to + ∆t) − VIb .Ib (to )

The natural reaction of pancreas for maintaining basal value of insulin is mathematically described
as P (t) = γ[Gb (t) − h]+ t whereas the term [Gb (t) − h]+ has some value for [Gb (t) − h] positive
and 0 otherwise. Now using mass balance rule we have:

accumulated = in − out + produced − used

accumulated = P (t) + (P rodbsl − clearance)
VIb .Ib (to + ∆t) − VIb .Ib (to ) = (QIb2 .[Gb (t) − h]+ .t.∆t) − (QIb1 .(Ib (t) − Ib )∆t)

Now dividing both sides by VIb and ∆t and applying the limit ∆t → 0 we get:

10
Chapter 2 Modeling of Glucose-Insulin Dynamics

dIb (t) QIb2 QIb1

= [Gb (t) − h]+ .t − (I − b(t) − Ib )
dt VIb VIb
QIb2 QIb1
Now by selecting γ = and n = we get the equation (2.5). The block diagram of glucose
VIb VIb
dynamics given in minimal model is given below:

Table 2.3: PARAMETERS USED IN INSULIN KINETICS DERIVATION

Parameters Description Unit
γ Shows rate of pancreatic beta cell’s release of insulin mUdL/(L.mg.min)
n First order decay rate for insulin in blood 1/min
h Threshold value of glucose concentration mg/dL
VIb Volume of insulin compartment L
QIb1 Flow rate of insulin L/min
QIb2 Flow of insulin mUdL/(mg.min)

2.2.4 Block Diagram for Insulin Dynamics

Figure 2.2: Dynamics of Insulin Concentration in Blood Plasma

2.3 Complete Model

The complete Bergman’s Minimal Model can be written in state-space form as follows:
dGb (t)
= −(p1 + Xb (t))Gb (t) + p1 Gb (2.6)
dt
dXb (t)
= −p2 Xb (t) + p3 (Ib (t) − Ib ) (2.7)
dt
dIb (t)
= −n(Ib (t) − Ib ) + γ[Gb (t) − h]+ t (2.8)
dt

11
Chapter 2 Modeling of Glucose-Insulin Dynamics

2.3.1 Block Diagram

Figure 2.3: Block diagram of Bergman’s minimal model

12
Chapter 3

Sliding Mode Control for Blood

Glucose Regulation in Diabetes
Patients

3.1 Introduction
Dealing any practical control problem, there exists difference between actual plant and its mathemat-
ical modeling used for designing a controller. These differences or mismatches result from external
disturbances, variation in parameters and dynamics which are not modeled. In order to design a
controller for closed-loop systems that provides desired performance in the presence of such mis-
matches is a challenging objective. This conception has led to the discovery of robust controllers.
Among robust controllers one of the most famous is sliding mode control (SMC) technique.

3.2 Sliding Mode Control

SMC is nonlinear control algorithm showing precious properties of robustness, accuracy and con-
venient tuning as well as implementation. SMC based controller design force system states onto
specific surface, belonging to state space of system, named sliding surface. Once system states
reach sliding surface, SMC maintains the system trajectories to the closest vicinity of sliding sur-
face. Hence design of SMC controller consists of two parts in principle. First part is appropriate
design of sliding surface, related to desired response specifications. Second part is using such con-
trol law that will keep system trajectories on sliding surface designed [37].

13
Chapter 3 Sliding Mode Control........

3.2.1 Reaching Phase

In SMC first of all the system trajectories are forced to reach the designed sliding manifold from their
initial points. This phase of reaching system trajectories to sliding manifold is termed as reaching
phase in SMC theory.

3.2.2 Sliding Phase

Once system trajectories reach sliding manifold, they are forced to stay on sliding surface without
leaving it and are forced to reach equilibrium point. This phase in which system trajectories slide
over surface is termed as sliding phase in SMC theory. Reaching and sliding phases are shown in
figure below [38]:

Figure 3.1: Reaching and Sliding Phase in SMC

3.3 SMC Based Controller Design

In this section sliding mode controller is designed for blood glucose regulation in type 1 diabetes
patients. The nonlinear state space model of glucose-insulin dynamics is give by:

dX1b (t)
= −(p1 + X2b (t))X1b (t) + p1 Gb + D(t) (3.1)
dt
dX2b (t)
= −p2 X2b (t) + p3 (X3b (t) − Ib ) (3.2)
dt

14
Chapter 3 Sliding Mode Control........

dX3b (t)
= −n(X3b (t) − Ib ) + u(t) (3.3)
dt
Where γ[Gb (t) − h]+ t term is zero in type 1 patients as there is no release of insulin by pancreas,
D(t) is external meal disturbance and u(t) is control input showing infusion of insulin.

3.3.1 Sliding Manifold

A general form of designing sliding manifold is given by:

d
S=[ + λ]r−1 e (3.4)
dt

Where r is the relative degree and e = X1b (t) − X1bref is output error. In this case r = 3 as control
input explicitly appears in third derivate of output Gb (t), so we have:

d
S=[ + λ]2 e (3.5)
dt

S = ë + λ1 ė + λ2 e (3.6)

Which is the required sliding manifold where λ1 and λ2 are design parameters.

3.3.2 Equivalent Control Law

In order to derive equivalent control law for SMC controller the lyapunov candidate function is
selected as:
1 2
V(X ) = S (3.7)
2
The derivative of lyapunov function will be:

V̇(X ) = S Ṡ
...
Ṡ = e + λ1 ë + λ2 ė
... ... ...
e = X 1b (t) − X 1bref
...
=⇒ e = ψ(X, t) − p3 X1b u(t)

Using minimal model of healthy person we have,

ψ(X, t) = [−p1 (p1 2 + 3p3 Ib ) − p3 Ib (p2 + n) − p3 γ[X1b (t) − h]+ t]X1b (t) + [−p1 2 (1 + Gb ) +
p1 p2 (2Gb − 1) + 2D(t)(p1 + p2 )]X2b (t)+
2
[−2p3 (p1 + D(t))]X3b (t) + [−(p1 + p2 ) − 3p3 Ib ]X1b (t)X2b (t)+
2
[p3 (3p1 + p2 + n)]X1b (t)X3b (t) + [−3(p1 + p2 )]X1b (t)X2b (t) +
2 3
(p1 Gb + D(t))X2b (t) + 3p3 X1b (t)X2b (t)X3b (t) − X1b (t)X2b (t) +
D̈(t) + (p1 Gb + D(t))(p1 2 + 2p3 Ib )
=⇒ Ṡ = ψ(X, t) − p3 X1b u(t) + λ1 ë + λ2 ė

15
Chapter 3 Sliding Mode Control........

Now the equivalent control law can be derived and is given by:

1
ueq (t) = (ψ(X, t) + λ1 ë + λ2 ė) (3.8)
p3 X1b

Using this control law we have:

Ṡ = 0
=⇒ V̇(X ) = 0

In order to make V̇(X ) negative definite for achieving asymptotic stability we have switching control
law which is described in next section.

3.3.3 Discontinuous Control Law

For the sake of achieving asymptotic stability in SMC, based on lyapunov theory, discontinuous
control law is used also known as switching control law. The switching control law used here is
given by:
usw (t) = k1 S + k2 sig(S) (3.9)

Where k1 and k2 are design parameters, which are tuned for achieving desired response. The overall
control law comes out to be:

1
u(t) = (ψ(X, t) + λ1 ë + λ2 ė + k1 S + k2 sig(S)) (3.10)
p3 X1b

Using this control law given in equation (3.10) derivative of lyapunov function becomes:

V̇(X ) = S(−k1 S − k2 sig(S))

=⇒ V̇(X ) = −k1 S 2 − k2 |S|

Thus V̇(X ) is negative definite which ensures asymptotic stability.

3.3.4 Simulation Results

This section includes the simulation results for analyzing the performance of derived SMC control
law given in equation (3.10).

16
Chapter 3 Sliding Mode Control........

Table 3.1: VALUES OF PARAMETERS USED FOR S IMULATION IN SMC A LGORITHM

Parameter Value
p1 0
p2 0.02
p3 0.0000053
γ 0
n 0.3
Ib 7
Gb 80
X1b (0) 250
X3b (0) 40
λ1 0.0331
λ2 0.00017225
k1 0.0199
k2 0.00053

3.3.4.1 Regulation of Glucose during Hyperglycemia

Figurer 3.2 shows stabilization of glucose concentration in blood plasma when the patient is in state
of hyperglycemia. The level of glucose is forced to the basal value in about 650 minutes.

Figure 3.2: Glucose concentration during hyperglycemia using SMC

17
Chapter 3 Sliding Mode Control........

Figure 3.3 shows the dynamical behavior of error appearing in glucose concentration of patient.
The output error is driven to zero in about 650 minutes thus bringing the concentration of glucose to
the normal value.

Figure 3.3: Output error during hyperglycemia using SMC

Figure 3.4 shows concentration of insulin in blood plasma. The phenomenon of chattering can
be observed, which is the main drawback of SMC algorithm. The concentration of insulin is driven
to the basal value successfully.

Figure 3.4: Insulin concentration during hyperglycemia using SMC

Figure 3.5 shows the infusion of insulin required for blood glucose regulation of diabetes patient,
which is the control input generated by SMC controller. There exists chattering in control input

18
Chapter 3 Sliding Mode Control........

which may be dangerous in practical implementation. To cope with the problem of chattering Super
Twisting SMC algorithm is used.

Figure 3.5: Control input during hyperglycemia using SMC

3.3.4.2 Regulation of Glucose during Hyperglycemia and Meal Disturbance

Figure 3.6: Meal disturbance used for simulation

Figure 3.7 shows the stabilization of blood glucose concentration in the presence of meal disturbance
which occurs at t = 500 min. Meal disturbance has an amplitude of 25 mg/dL but lasts for about 25
minutes. It can be observed that concentration of glucose in blood plasma is brought to normal value
i.e. 80 mg/dL.

19
Chapter 3 Sliding Mode Control........

Figure 3.7: Glucose concentration in presence of meal disturbance using SMC

Figure 3.8 depicts kinetics of output error. It is clear that when disturbance is added to the
system, the error is rapidly increased to about 160mg/dL, which is forced back to zero, it can be seen
in given figure.

Figure 3.8: Output error during meal disturbance using SMC

Figure 3.9 shows the concentration of insulin in blood plasma. Once disturbance appears at t =
500 min, insulin rapidly rises to lower the glucose concentration to normal. The intrinsic property
of classical SMC, chattering can be observed in the given figure.

20
Chapter 3 Sliding Mode Control........

Figure 3.9: Insulin concentration in presence of meal disturbance using SMC

Figure 3.10 is a picture of control input, the infusion of insulin into patient. A peak can be
noticed at the instant where disturbance is added to the system. This rapid increase in insulin infusion
is due to rapid increase in glucose in the form of disturbance. Chattering can be noticed in the given
figure.

Figure 3.10: Control input in presence of meal disturbance using SMC

21
Chapter 3 Sliding Mode Control........

3.3.4.3 Regulation of Glucose in Presence of 3 Meal Disturbance

Figure 3.11: Three meal disturbance used for simulation

Figure 3.12 shows the regulation of blood glucose concentration in the presence of three meal intakes
corresponding to break fast, lunch and dinner. It is clear from the figure that the blood glucose
concentration is stabilized successfully.

Figure 3.12: Glucose concentration in presence of 3 meal disturbance using SMC

Figure 3.13 shows the concentration of insulin in blood plasma. Rise in insulin level correspond-
ing to meal intakes can be observed, in order to lower the blood glucose concentration to normal.
Phenomenon of chattering is clear in the figure which is due to discontinuous control law of classical
SMC.

22
Chapter 3 Sliding Mode Control........

Figure 3.13: Insulin concentration in presence of 3 meal disturbance using SMC

Figure 3.14 shows the infusion of insulin, control input generated by SMC controller in the
presence of three meal intakes. The three peaks appearing in control input are due to rapid increase
in glucose level corresponding to meal intake. Chattering is obvious in the given figure.

Figure 3.14: Control input in presence of 3 meal disturbance using SMC

3.3.5 Drawbacks of Classical SMC

The main disadvantages of classical SMC algorithm based controller are given, which can also be
observed in simulation results provided.

• Slow transient response of the controller

23
Chapter 3 Sliding Mode Control........

• Large reaching time

• High frequency fluctuations in control input i.e. chattering

3.4 Super Twisting SMC

Due to the undesirable and dangerous phenomenon of chattering appearing in classical SMC algo-
rithm based controller, classical SMC is not often used in practical control problems. An alternative
and effective solution to the problem of chattering is higher order SMC technique. In our case a
special type of second order SMC is designed named Super Twisting SMC (STSMC) algorithm. Us-
ing STSMC algorithm we can achieve the finite convergence of sliding manifold used in controller
design. Due to continuous nature of switching control law, phenomenon of chattering can also be
reduced using STSMC algorithm based controller, without degrading the robustness, transient re-
sponse and steady state response of the system.

3.4.1 STSMC Based Controller Design

In this section super twisting sliding mode controller is designed for blood glucose regulation in type
1 diabetes patients.

3.4.1.1 Sliding Manifold

The sliding manifold as same as chosen for SMC algorithm.

S = ë + λ1 ė + λ2 e (3.11)

3.4.1.2 Equivalent Control Law

It can be derived in the similar way as done for SMC and is given by:
1
ueq (t) = (ψ(X, t) + λ1 ë + λ2 ė) (3.12)
p3 X1b

3.4.1.3 Switching Control Law

The switching algorithm used in super twisting sliding mode controller is given by:
1
2
usw (t) = η1 |S| sign(S) + ν (3.13)

Where ν̇ = η2 sign(S)
So the switching law comes out to be:
1 Z
usw (t) = η1 |S| 2 sign(S) + η2 sign(S)dτ (3.14)

24
Chapter 3 Sliding Mode Control........

Table 3.2: VALUES OF PARAMETERS USED FOR S IMULATION IN STSMC A LGORITHM

Parameter Value
p1 0
p2 0.02
p3 0.0000053
γ 0
n 0.3
Ib 7
Gb 80
X1b (0) 250
X3b (0) 40
λ1 0.0199
λ2 0.0003975
η1 0.000795
η2 9.275 × 10−11

3.4.2 Simulation Results

In this section simulation results are provided showing the performance of STSMC based controller.

3.4.2.1 Regulation of Glucose during Hyperglycemia

Figure 3.15 shows regulation of blood glucose level using STSMC based controller. It can be seen
that reaching time is improved and basal level is achieved in about 460 minutes.

25
Chapter 3 Sliding Mode Control........

Figure 3.15: Glucose concentration during hyperglycemia using STSMC

Figure 3.16 is a picture of error in glucose concentration. The error is reduced to zero suc-
cessfully in about 460 minutes, showing better performance as compare to classical SMC based
controller.

Figure 3.16: Output error during hyperglycemia using STSMC

Figure 3.17 explains concentration of insulin in blood plasma. It can be noted that level of
insulin is smooth and do not have chattering. So, using STSMC based controller the problem of
chattering is eliminated successfully.

26
Chapter 3 Sliding Mode Control........

Figure 3.17: Insulin concentration during hyperglycemia using STSMC

Figure 3.18 shows the infusion of insulin by pump into patient. The control input is smooth
having no chattering like classical SMC algorithm.

Figure 3.18: Control input during hyperglycemia using STSMC

3.4.2.2 Regulation of Glucose during Hyperglycemia and Meal Disturbance

Figure 3.19 depicts the performance of STSMC algorithm when the subject is exposed to meal
disturbance, which enters the system at time 450 min. It can be seen that the level of glucose is
forced back to basal value successfully.

27
Chapter 3 Sliding Mode Control........

Figure 3.19: Glucose concentration in presence of meal disturbance using STSMC

Figure 3.20 shows the dynamical behavior of output error. Error is reduced to zero in the pres-
ence of meal disturbance at time t = 1050 min.

Figure 3.20: Output error during meal disturbance using STSMC

Figure 3.21 shows the concentration of insulin in blood. It can be noted that concentration of
insulin is smooth having no chattering anymore.

28
Chapter 3 Sliding Mode Control........

Figure 3.21: Insulin concentration in presence of meal disturbance using STSMC

Figure 3.22 gives the dynamics of control input generated by STSMC based controller. It is
obvious that there is no chattering in control input, the infusion of insulin to patient is smooth.

Figure 3.22: Control input in presence of meal disturbance using STSMC

3.4.2.3 Regulation of Glucose in Presence of 3 Meal Disturbance

Figure 3.23 shows the regulation of glucose in the presence of three meal intakes using STSMC
based controller. Finally the blood glucose concentration is stabilized at its basal value.

29
Chapter 3 Sliding Mode Control........

Figure 3.23: Glucose concentration in presence of 3 meal disturbance using STSMC

Figure 3.24 is a picture of output error. The behavior of error is consistent with the output.

Figure 3.24: Output Error in presence of 3 meal disturbance using STSMC

Figure 3.35 shows concentration of insulin in blood compartment. The three peaks appearing in
graph are due to the disturbance added at these instances. The behavior of insulin concentration is
smooth having no fluctuations of high frequency.

30
Chapter 3 Sliding Mode Control........

Figure 3.25: Insulin concentration in presence of 3 meal disturbance using STSMC

Figure 3.26 shows the control input, infusion of insulin by pump into patient. The control input
is smooth and the phenomenon of chattering is eliminated using STSMC algorithm for designing the
controller.

Figure 3.26: Control input in presence of 3 meal disturbance using STSMC

31
Chapter 4

Backstepping Integral Sliding Mode

Control for Blood Glucose
Regulation in Diabetes Patients

4.1 Introduction
There are two major objectives, while designing a controller for regulation of blood glucose con-
centration in diabetes patients. Firstly, the controller should be robust against external disturbances
and mismatches. As it is concerned to human body so the controller must be accurate and precise in
its operation. Secondly, the blood glucose concentration should be stabilized in reasonable amount
of time. There is no well defined reaching time as different subjects have different glucose-insulin
dynamics, however reaching time should not be less then two hours. In order to obtain the two
objectives mentioned above a backstepping integral sliding mode control (BISMC) algorithm is in-
troduced. SMC is known for its robustness against mismatches and external disturbances where as
backstepping is used for reducing the reaching time of glucose concentration in blood plasma of
patient. The derivation of control law based on BISMC is given and simulation results are presented
for analyzing the performance of proposed controller.

4.2 Backstepping Control

Backstepping control (BC) is a control algorithm used for specific class of nonlinear systems, for
designing stable controls [39,40]. The system is divided into small subsystems, controllers are de-
signed starting from the first state and the process continues until the real control law u(t) appears,
hence this process is named backstepping [41].

32
Chapter 4 Backstepping Integral Sliding Mode Control........

4.3 Backstepping Integral Sliding Mode Control

In this section the BISMC algorithm is derived for blood glucose regulation of diabetes patient based
on Bergman’s minimal model of glucose-insulin dynamics.

4.3.1 Derivation of Control Law

The state space model of glucose-insulin kinetics is given by:

dx1b (t)
= −(p1 + x2b (t))x1b (t) + p1 Gb + D(t) (4.1)
dt
dx2b (t)
= −p2 x2b (t) + p3 (x3b (t) − Ib ) (4.2)
dt
x3b (t)
= −n(x3b (t) − Ib ) + u(t) (4.3)
dt
The system is already in strict-feedback form and we can apply backstepping. The first equation is
given by:
dx1b (t)
= −(p1 + x2b (t))x1b (t) + p1 Gb + D(t)
dt
dx1b (t)
= −p1 x1b (t) − z1 (t)x1b (t) + p1 Gb + D(t)
dt
Where z1 (t) is virtual control input. The sliding manifold for deriving z1 (t) is selected as:
R
S1 = e1 + c1 e1 dτ

Where e1 = x1 (t) − Gb ,

Ṡ1 = ė1 + c1 e1
⇒ Ṡ1 = ẋ1 − Ġb + c1 e1
⇒ Ṡ1 = −p1 x1b (t) − z1 (t)x1b (t) + p1 Gb + D(t) + c1 e1
1
z1 (t) = (−p1 x1b (t) + p1 Gb + D(t) + c1 e1 ) (4.4)
x1b (t)
The second equation is given by:

ẋ2b (t) = −p2 x2b (t) + p3 (x3b (t) − Ib )

⇒ ẋ2b (t) = −p2 x2b (t) + p3 z2 (t) − p3 Ib

The sliding manifold is selected as:

R
S2 = e2 + c2 e2 dτ

Where e2 = x2b (t) − z1 (t),

Ṡ2 = ė2 + c2 e2
⇒ Ṡ2 = ẋ2b − ż1 (t) + c2 e2
⇒ Ṡ2 = −p2 x2b (t) + p3 z2 (t) − p3 Ib − ż1 (t) + c2 e2

33
Chapter 4 Backstepping Integral Sliding Mode Control........

The second virtual control comes out to be:

1
z2 (t) = (p2 x2b (t) + p3 Ib + ż1 (t) − c2 e2 ) (4.5)
p3
The final equation of model is given by:

ẋ3b (t) = −n(x3b (t) − Ib ) + u(t)

The sliding manifold is selected as:

R
S3 = e3 + c3 e3 dτ

Where e3 = x3b (t) − z2 (t),

Ṡ3 = ė3 + c3 e3
⇒ Ṡ3 = ẋ3b − ż2 (t) + c3 e3
⇒ Ṡ3 = −n(x3b (t) − Ib ) + u(t) − ż2 (t) + c3 e3

Finally the control input comes out to be:

u(t) = n(x3b (t) − Ib ) + ż2 (t) − c3 e3 (4.6)

The switching control for keeping the dynamics on the proposed sliding surface is given by:

usw (t) = −k1 S3 − k2 sign(S3 ) (4.7)

The overall control law becomes:

u(t) = n(x3b (t) − Ib ) + ż2 (t) − c3 e3 − k1 S3 − k2 sign(S3 ) (4.8)

4.3.2 Simulation Results

Table 4.1: VALUES OF PARAMETERS USED FOR S IMULATION IN BISMC A LGORITHM

Parameter Value
c1 0.012
c2 0.6
c3 0.05
k1 0.0007
k2 1.6

4.3.2.1 Regulation of Glucose during Hyperglycemia

Figure 4.1 shows regulation of blood glucose level using BISMC based controller. It can be seen
that reaching time is improved and basal level is achieved in about 360 minutes.

34
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.1: Glucose concentration during hyperglycemia using BISMC

Figure 4.2 explains concentration of insulin in blood plasma. Concentration of insulin in blood
plasma is stabilized within about 350 minutes using BISMC based controller. It can be seen that
reaching time is improved, also no chattering is there.

Figure 4.2: Insulin concentration during hyperglycemia using BISMC

Figure 4.3 shows the infusion of insulin by pump into patient. The control input is smooth
having no chattering like classical SMC algorithm.

35
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.3: Control input during hyperglycemia using BISMC

4.3.2.2 Regulation of Glucose during Hyperglycemia and Meal Disturbance

Figure 4.4 depicts the performance of BISMC algorithm when the subject is exposed to meal dis-
turbance, which enters the system at time 400 min. It can be seen that the level of glucose is forced
back to basal value successfully.

Figure 4.4: Glucose concentration in presence of meal disturbance using BISMC

Figure 4.5 shows the concentration of insulin in blood. It can be noted that concentration of
insulin is smooth having no chattering anymore. The reaching time is also reduced.

36
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.5: Insulin concentration in presence of meal disturbance using BISMC

Figure 4.6 gives the dynamics of control input generated by BISMC based controller. It is
obvious that there is no chattering in control input, the infusion of insulin to patient is smooth.

Figure 4.6: Control input in presence of meal disturbance using BISMC

4.3.2.3 Regulation of Glucose in Presence of 3 Meal Disturbances

Figure 4.7 shows the regulation of glucose in the presence of three meal intakes using BISMC based
controller. Finally the blood glucose concentration is stabilized at its basal value.

37
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.7: Glucose concentration in presence of 3 meal disturbance using BISMC

Figure 4.8 shows concentration of insulin in blood compartment. The three peaks appearing in
graph are due to the disturbance added at these instances. The behavior of insulin concentration is
smooth having no fluctuations of high frequency.

Figure 4.8: Insulin concentration in presence of 3 meal disturbance using BISMC

Figure 4.9 shows the control input, infusion of insulin by pump into patient. The control input
is smooth. Level of insulin rapidly increases as meal disturbance appears, as a result blood glucose
level is stabilized.

38
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.9: Control input in presence of 3 meal disturbance using BISMC

4.4 Comparative Analysis

In this section SMC, STSMC and BISMC controllers are compared and analyzed to clarify the
advantages and performance of BISMC based controller for blood glucose regulation of diabetes
patients.

4.4.0.1 Regulation of Glucose during Hyperglycemia

Figure 4.10 shows the blood glucose regulation of diabetes patient during hyperglycemia using SMC,
STSMC and BISMC based controllers. The basal value is taken as 80 mg/dL. It is clear from the
figure that reaching time of BISMC based controller is less then other two controllers.In case of
BISMC algorithm the blood glucose level is stabilized at about 350 minutes, which is reasonable
reaching time.

39
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.10: Comparison of glucose concentration during hyperglycemia

Figure 4.11 depicts the concentration of insulin in blood of patient during hyperglycemia using
SMC, STSMC and BISMC algorithms. SMC based controller shows chattering which is not desir-
able. However, using BISMC algorithm the concentration of insulin varies smoothly, reaching to
basal value.

Figure 4.11: Comparison of insulin concentration during hyperglycemia

Figure 4.12 shows the insulin infusion rate for three controllers. Smooth and accurate behavior
of BISMC based controller is obvious.

40
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.12: Comparison of control inputs during hyperglycemia

4.4.0.2 Regulation of Glucose during Hyperglycemia and Meal Disturbance

Figure 4.13 shows regulation of blood glucose level in the presence of meal disturbance using three
different controllers.The performance of BISMC based controller is clear in the figure.

Figure 4.13: Comparison of glucose concentration in presence of meal disturbance

Figure 4.14 is a picture of insulin concentration in blood plasma. The peaks appearing in BISMC
based controller are due to its quick response and low reaching time.

41
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.14: Comparison of insulin concentration in presence of meal disturbance

Figure 4.15 shows the control input during hyperglycemia and meal disturbance. Initially more
amount of insulin is injected using BISMC algorithm because of its fast transient response.

Figure 4.15: Comparison of control inputs in presence of meal disturbance

4.4.0.3 Regulation of Glucose in Presence of 3 Meal Disturbance

Figure 4.16 shows stabilization of glucose level in the presence of three meal intakes by the pa-
tient. The performance of BISMC based controller is clear that its response is fast and accurate as
compared to SMC and STSMC based controllers.

42
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.16: Comparison of glucose concentration in presence of 3 meal disturbance

Figure 4.17 shows the dynamics of insulin in blood plasma during three meal intakes by the
patient. BISMC based controller has no chattering and is maintaining basal level successfully.

Figure 4.17: Comparison of insulin concentration in presence of 3 meal disturbance

Figure 4.18 shows the insulin injection rate of pump in the presence of three meal intakes by the
patient.

43
Chapter 4 Backstepping Integral Sliding Mode Control........

Figure 4.18: Comparison of control inputs in presence of 3 meal disturbance

44
Chapter 5

Conclusion and Future Work

5.1 Conclusion
Robust control of blood glucose concentration in type 1 diabetes patients has been an active area
of research for many decades. This thesis is an attempt to design a robust nonlinear controller for
automatic insulin pumps, in order to regulate blood glucose level in type 1 diabetes patients. Sliding
Mode Control (SMC) based three algorithms were developed and investigated. Traditional SMC
algorithm was designed for blood glucose regulation in type 1 diabetes patients. Bergman’s minimal
model was used for controller design. It has been observed that CSMC show chattering (fluctuations
of high frequency) appearing in control action. STSMC was introduced and designed for getting
rid of chattering phenomenon in control action. STSMC showed smooth control action but tran-
sient response was still comparatively slow. For obtaining suitable performance BISMC algorithm
was introduced and designed. BISMC controller showed best results and can be used for blood
glucose regulation of diabetes patients in artificial pancreas. Main disadvantages of previous con-
trollers include risk of hypoglycaemia, robustness, chattering in classical SMC and more control
effort required. A novel BISMC algorithm has been developed for tackling the challenges regard-
ing regulation of blood glucose concentration in type 1 diabetes patients. Proposed controller was
analyzed for three cases. Firstly, hyperglycemia i.e when blood glucose level of patient is danger-
ously high. Secondly, hyperglycemia and meal disturbance. Finally, case of three meal intakes was
investigated. It has been showed that proposed controller show satisfactory results in stabilizing
blood glucose level by reasonable injection rate of insulin to diabetic patient in question. Designed
controller can be a suitable choice for closed loop automatic insulin pumps.

45
Chapter 5 Conclusion and Future Work

5.2 Future Work

The research work done and presented can be extended in future to obtain more accurate and optimal
performance. The following extensions can be made to the present research work.

• Using advance optimization techniques for tuning of BISMC controller can result in more optimal
control performance

• Using detailed physiological model for deriving controller may result in more accurate perfor-
mance.

• Using adaptive laws for parameters estimation can further increase robustness of the controller.

46
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