UMMiSITI MALAYSIA SABAH

SURVIVAL ANAL YSIS OF DIABETIC PATIENTS IN QUEEN ELIZABETH

HOSPITAL, KOTA KINABALU

WONG YEW LEONG

Ytlll-u.) II" .. \/"\1 ~

UMMiSITI MALAYSIA SABAH

THIS DISSERTATION IS SUBMITTED AS PART OF THE PRE-REQUIREMENT TO

BE CONFERRED THE DEGREE IN BACHELOR OF SCIENCE IN MA THEMA TICS

WITH ECONOMICS

PROGRAMME MA THEMA TICS WITH ECONOMICS

SCHOOL OF SCIENCE AND TECHNOLOGY

UNIVERSITY MALAYSIA SABAH

APRIL 2007

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I (HURUF BESAR)

mcngal..-u mcmbenarkan tesis (LPSlS~kt~safah)· ini.disimpan di Pcrpustakaan Univcrsiti Malaysia Sabah dcng'~n syarat-syarnt kegunaan scpctti berikut

I. Tesis adalab bakmilik Universiti Malay,tia Sabah. 2. ~ell'ustakaan Universiti Malaysia SAbah dibenarkan membuat salinan untuk tujuan pengajian sabaja. 3. PCll'ustakaan dibcnarkao membuat s:dilu.n tcsis ini scbagai bahan pcrtukaran antara institusi pengajian

tinggi. 4. ""Sila tandakan ( I )

SULIT

[2J TERHAD

D TIDAK TER1{AD

~ (TANDA TANGAN PENULtS)

Ala.m.1t Tctap:_ q" jJ.M Ik.T ttLlSIt ~, TMN " A:. T ~Etl SA

Tarjk.h: __ ~":"if-ll4~jf-( ,:~:t!..-.-___ _ .~

CAT A TAN: " Potong yang tidak bcrkcnaan.

(Mcngandungi maldumat yang berdaIjah keselamatan. atau kepcnti!lgan Malaysia scpecti yang tetmaktub di dalam AKTA:RAliSIA RASMI t912)

(Mengandungi maldumat TERHAD yang tclah ditentukan oleh organisasilbadan di maoa penyclidikan dijalankan)

Pli. flTI klrlj~y, '7·IItDIlD A9 ~.., Nama Penydia

Tarikh: __________ _

. a. Jika tcsis ini SULIT atau TERHAD. sill! lampirkan sura! daripada pihak bcrIcua.worganisasi herken3..al\ dengan menyatakan sekaJi scbab dan tcmpoh I~is ini pcrlu dilccbskan scbagai SULIT dan TERHAD.

@ Tcsis dimaksudkan scbagai tcsis bagi Iju..ah Doktor Falsa!:.&h dan Sasjana secara penyelidil:an, i!.t3U

discltasi bag; pcncajian sccara kclja kUrnJs dan pcnyelidik.an. atau Laporan Projck Sarjana Muda (LPSM).

ii

DECLARATION

I declared that this dissertation is my original work except for the quotations and

summary that has been cited in the reference.

20 April 2007

WONG YEW LEONG

(HS 2004-1813)

iii

CERTIFIED BY

Signature

1. SUPERVISOR

(pN. sm RAHAYU BT. MOHD HASHIM)

2. EXAMINER 1

(pN. SURIANI BT. HASSAN)

3. DEAN )~~'1-(ASSOCIATE PROF. DR. SHARIFF AK OMANG) _---'-~ ____ _

UMS UNIVERSITI MALAYSIA SABAH

IV

ACKNOWLEDGEMENT

First and foremost, I would like to express my deepest gratitude to my supervisor,

Pn. Siti Rahayu for her guidance and time in helping me to fInish up the dissertation on

time. She has given lots of suggestions and guidance regarding the running of the analysis.

She also mentioned what are the essential items that are needed in each section so that I

would not miss out any important information. Next, I would also express my thanks to

my friends especially Ai Chang, Nick and Yee Chi for their support. They have also

given me suggestions. We have spent time discussing the appropriate infonnation needed

from the fIrst chapter to the end. Next, I would like to thank the staffs in Queen Elizabeth

Hospital especially Mr. Dominique and Mr. Abdul Rahman for their dedication and time

in fulfIlling my needs for this dissertation. They were patience in answering all my

questions. Not forgetting my family for their uncountable moral supports. I would not

forget their dedication and involvement although they are getting nothing from their

contributions.

Finally, I would also like to express my deepest gratitude to all the other

anonymous members whose names I can't remember for their contributions to this

dissertation. Without the help and guidance of all those involved, this dissertation might

not have been completed.

ANALISIS MANDIRI PESAKIT DIABETES DI HOSPITAL QUEEN

ELIZABETH, KOTA KINABALU

ABSTRAK

v

Diabetes merupakan salah satu penyumbang utama terhadap kematian yang melibatkan

penyakit bukan sahaja di Malaysia malahan di seluruh dunia. Oleh yang demikian, adalah

penting sekiranya aliran ataupun golongan umur utama yang menghidapi penyakit ini

dapat ditentukan agar pihak yang berwajib dapat melaksanakan usaha bagi menurunkan

kadar kematian penyakit ini. Objektifutama kajian ini dilakukan adalah untuk melakukan

analisis kemandirian bagi menentukan kadar kemandirian pesakit diabetes di Sabah,

menentukan aliran kemandirian pesakit diabetes, menghitung fungsi mandiri, fungsi

ketumpatan dan fungsi hazard melalui jadual sifir usia dan menentukan samada wujudnya

perbezaan 'secara bererti antara jantina, etnik dan kategori umur yang menghidapi

penyakit ini dengan menggunakan ujian log-rank. Data pesakit telah diarnbil dari Hospital

Queen Elizabeth (QEH), Kota Kinabalu, Sabah. Pembolehubah yang diperlukan dalam

kajian ini adalah, jantina, umur, jangka hayat kemandirian dan etnik. Fungsi kemandirian,

fungsi ketumpatan dan fungsi hazard digunakan. Plot penganggar Kaplan-Meier

diplotkan sebagai sokongan bagi penentuan kadar kemandirian bagi pesakit diabetes di

Sabah. Didapati bahawa fungsi mandiri pesakit diabetes adalah tinggi manakala

kebarangkalian ketumpatan dan kadar hazard adalah rendah. Keputusan juga

menunjukkan bahawa tiada wujudnya perbezaan secara hererti antara jantina, etnik dan

kategori umur. Ini hermakna bahawa semua orang mempunyai risiko yang sarna

menghidapi penyakit ini tanpa mengira jantina ataupun etnik.

vi

ABSTRACT

Diabetes has been known as one of the major contribution of mortality not only in

Malaysia but also around the world. Hence, it is important if the trend or the major groups

suffered by this disease can be determined so that they can benefit through efforts by

major parties to lower the risk of death. The objectives of this research are to conduct a

survival analysis to detennine the survival rate of diabetic patients, to determine the trend

of survival in diabetic patients, to compute survival function, density function and hazard

function from life table and to determine whether significance difference exists among

genders, ethnics and ages by using log-rank test. The data was collected from Queen

Elizabeth Hospital (QEH). The variables included in this study are gender, age, time of

survival and ethnics. Survival function, density function and hazard function were used.

Log-rank test was also perfonned in this dissertation to compare between two factors to

determine whether significant difference existed in the variables or not. Kaplan-Meier

estimator plot was also plotted to determine the survival pattern of the patients with

diabetes in Sabah. It showed that the survival function of diabetic patients was high while

the density probability and hazard rate was low in Sabah. The result also showed there

was no significance difference existed among genders, ethnics and ages. This implied that

all of them had the same risk in being diagnosed with this disease regardless of genders

and ethnics.

vii

TABLE OF CONTENTS

Page

DEC LARA TION ii

CERTIFIED BY III

ACKNOWLEDGEMENT iv

ABSTRAK v

ABSTRACT vi

TABLE OF CONTENTS Vll

LIST OF TABLES x

LIST OF FIGURES xi

LIST OF ABBREVIATIONS xiii

LIST OF SYMBOLS xiv

CHAPTER 1 INTRODUCTION 1

1.1 Diabetes 2

1.1.1 The History of Diabetes 2

1.1.2 Type 1 Diabetes 4

1.1.3 Type 2 Diabetes 4

1.1.4 Gestational Diabetes 5

1.1.5 Main Complications of Diabetes 5

1.2 Current Issues 6

1.2.1 Diabetes in the World 8

viii

1.2.2 Diabetes in Asia 8

1.2.3 Diabetes in Malaysia 9

1.3 Survival Analysis 12

1.3.1 Life Table Analysis 13

1.3.2 Kaplan-Meier Estimator 13

1.3.3 Log-Rank Test 14

1.3.4 Cox Proportional Hazard Model 15

1.3.5 Censored Data 16

1.4 Objectives 17

1.5 Scope of Study 18

CHAPTER 2 LITERATURE REVIEW 19

2.1 Past Researches on Diabetes 19

2.2 Past Researches on Survival Analysis 25

CHAPTER 3 METHODOLOGY 29

3.1 Introduction 29

3.2 Variables of the Research 30

3.3 Data Source and Subject 30

3.4 Life Table 31

3.5 Survival Function 33

3.6 Density Function 36

3.7 Hazard Function 38

3.8 Kaplan-Meier Estimator 40

3.9 Log-Rank Test 41


ix

CHAPTER 4 RESULTS AND DATA ANALYSIS 45

4.1 Sample 45

4.2 Descriptive Analysis 45

4.3 Life Table 51

4.4 Survivorship Function 52



4.7 Kaplan-Meier Plot 66


CHAPTER 5 DISCUSSION 81

5.1 Genders 81

5.2 Ethnics 83

5.3 Age 85

5.4 Survivorship Function 86




CHAPTER 6 CONCLUSION AND SUGGESTIONS 92

LIST OF REFERENCES 94

APPENDICES

LIST OF TABLES

Table Number

1.3 Adult obesity in 2002 and estimated level in 2010, expressed

as percent of people ~ 15 years of age with BMI~30

Page

10

1.4 Diabetes prevalence in people over 20 years of age in 2000 and predicted 11

for 2030 in countries with more than 100 million inhabitants

3.1 Variables of the research 30

4.19 Table showing the summary of deaths and censoring occurred according 70

to genders

4.21 The value of chi-square and its significance value for log-rank test 72

4.22 Computations of E/ and E2 of log-rank test 74


to ethnics



to categories of ages


5.1 Vital population statistics based on 1991 census of people living in Kota 84

Kinabalu

x

xi

LIST OF FIGURES

Figure Number Page

1.1 The number of diabetic patients in 2010 7

1.2 The estimated number of diabetic patients in 2030 7

1.5 An example of Kaplan-Meier estimator plot 14

4.1 The number of female and male diabetic patients in QEH with 1 46

represents male and 2 represents female

4.2 The number of diabetic patients in QEH based on ethnics 47

4.3 The pie chart showing the number of diabetic patients admitted to QEH 48

based on percentage

4.4 The histogram above shows the number of patients that were registered 49

in QEH based on the age factor

4.5 The figure above shows the status of diabetic patients in QEH 50

4.6 Survival function of diabetic patients admitted to QEH, Kota Kinabalu 53


divided into male and female


divided into ethnics


divided into different categories of ages

4.10 Density function of diabetic patients admitted to QEH, Kota Kinabalu 57

Xli


divided into male and female patients




divided into categories of ages

4.14 Hazard rate of diabetic patients admitted to QEH, Kota Kinabalu 63




divided into ethnics


divided into categories of ages

4.18 Kaplan-Meier plot for the diabetic patients in QEH for year 2005 67

4.20 Log-rank plot for the factor of genders 71

4.24 Log-rank plot for the factor of ethnics 77

4.28 Log-rank plot for the factor of ages 80

Xlll

LIST OF ABBREVIATIONS

ADA American Diabetes Association

BC Before Christ

BMl Body Mass Index

CDC Centers for Disease Control

CHF Congestive Heart Failure

CPHM Cox Proportional Hazard Model

DCCT Diabetes Control and Complication Trials

HRQoL Health-related Quality of Life

IDDM Insulin-dependent Diabetes Mellitus

NDFS National Diabetes Fact Sheet

NHS Nurses' Health Study

NIIDM Non-insulin-dependent Diabetes Mellitus

OR Odds ratio

PL Product Limit

POAG Primary Open-angle Glaucoma

QEH Queen Elizabeth Hospital

RR Rate Ratio

SMR Standardized Mortality Ratio

SPSS Statistical Packages for Social Sciences

UN United Nations

WHO World Health Organization

xiv

LIST OF SYMBOLS

% Percentage

> more than

> more than or equal to

< less than or equal to

< less than

± plus-minus sign

/ over

00 infinity

= equal

At delta t

At~O limit as delta t approaches 0

f- not equal to

I chi-square

L summation

(l alpha

;:::: almost equal to

CHAPTERl

INTRODUCTION

Diabetes has been known as one of the major contribution of mortality not only in

Malaysia but also around the world. In America alone, according to the latest figure

released by Department of Health and Services under Centers for Disease Control (CDC)

in 2005, the total prevalence of diabetes by all ages were estimated at 20.8 million people

or around 7.0% of the total population in America. Although the percentage rate was

overall quite low, recent researches that were conducted in the past few years sensed that

the trend was growing continuously particularly in the 60 and above age category. Now,

about one in every four hundred to six hundred children and adolescents has Type 1

Diabetes and the people under the 60 and above age category accounted for 20.9010 of

total cases (National Diabetes Fact Sheet United States, 2005). In Malaysia, diabetes was

placed second behind heart disease for the total number of death. Detailed researches on

the mortality rate of diabetes have not been done thoroughly in Malaysia. Hence, it is

important if the trend or the major groups suffered by this disease can be determined so

that they can benefit through efforts by major parties to lower the risk of death. To do so,

2

estimation of mortality rates in diabetes in Malaysia need to be conducted by using

survival analysis techniques. Among them are Kaplan-Meier estimators, survival, density

and hazard function. By conducting these tests, the survival rates of patients suffering

from diabetes can be calculated.

1.1 Diabetes

Diabetes is a group of diseases marked by high level of glucose resulting from defects in

insulin production, insulin action or both. It can lead to serious complications and

premature death but steps to control the disease and lower the risk of complications do

exist. Diabetes was divided into two main different types of diabetes which are Type 1

and Type 2 Diabetes. The fonner was previously called insulin-dependent diabetes

mellitus (IDDM) or juvenile-onset diabetes while the latter was previously called non

insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes (National Diabetes

Fact Sheet United States, 2005).

1.1.1 The History of Diabetes

History of diabetes has begun since it was first discovered on papyrus by Ebers in Egypt,

1552 B.C. The first diabetes word was used was by Aretaeus of Cappadocia in the late

second century B.C. In 1869, Paul Langerhans, a Gennan medical student, announced in

a dissertation that the pancreas contains two systems of cells. One set secretes the normal

pancreatic juice; the function of the other was unknown. Several years later, these cells

3

were identified as the islets of Langerhans. History tributed Oskar Minkowski and Joseph

von Mering for their discovery that the pancreas played a major role in diabetes in the

year 1889. These Europeans discovered that when they took the pancreas out of animals,

they exhibited all the indicators associated with diabetes. At the beginning of the

twentieth century, Edward Sharpey-Schafer, a Scot, hypothesized that those suffering

from diabetes were lacking a substance that was made by the pancreas. He named this

chemical insulin.

In 1921, it was Frederick Grant Banting and Charles Herbert Best who continued

diabetes research. Their experiments showed that diabetes symptoms and risk factors

could be reduced by transferring pancreatic insulin from healthy dogs to diabetic dogs.

For this amazing discovery, Frederick Banting later received the Nobel Prize. Insulin

became widely available worldwide within a very short period of time.

Most the other major historical achievements of diabetes treatment had happened

during these years. In 1922, Leonard Thompson was the first person to be injected with

insulin in Toronto. In 1934, the first national diabetes association was formed, Diabetic

Association, in U.K. In 1970, the first glucose meter was developed. In 1983, first

biosynthetic human insulin was introduced. In 1993, Diabetes Control and Complications

Trial (DCCT) report was published. The DCCT results clearly demonstrate that intensive

therapy (more frequent doses and self-adjustment according to individual activity and

eating patterns) delays the onset and progression of long-term complications in

individuals with type 1 diabetes (Canadian Diabetes Association, 2006).

4

1.1.2 Type 1 Diabetes

IDDM developed when the body's immune system destroyed pancreatic beta cells, the

only cell in the body that makes the honnone insulin that regulated blood glucose. In

other word, it occurred when the body was unable to produce any insulin. To survive,

people with IDDM must have insulin injected or pumped. It usually strikes children and

young adults that accounted for 5% to 10% of total diagnosed cases of diabetes.

According to CDC, risk factors for Type 1 Diabetes may be autoimmune, genetic or

environmental. Several clinical trials of methods of the prevention of this disease are

currently in progress or are being planned since there is still no known way to prevent this

disease (National Diabetes Fact Sheet United States, 2005).

1.1.3 Type 2 Diabetes

Most of the diagnosed cases of diabetes were of Type 2 Diabetes which accounted for

about 90% to 95% of total cases. It usually begins as insulin resistance, a disorder in

which the cells do not use the insulin properly. As the need for insulin rises, the pancreas

gradually loses its ability to produce it. In other word, it means that the body was still

producing insulin but not enough. Type 2 Diabetes is associated with older age, obesity,

family history of diabetes, history of gestational diabetes, impaired glucose metabolism,

physical inactivity and raceiethnicity (National Diabetes Fact Sheet United States, 2005).

5

1.1.4 Gestational Diabetes

Another type of diabetes that occurred was called gestational diabetes which affected

women during pregnancy in which it was a form of glucose intolerance. It was also more

common among obese women and women with a family history of diabetes. During the

pregnancy period, they were required to be treated to normalize maternal blood glucose

level to avoid complications in the infant. It was said that about 5% to 10% of these

women would suffered from Type 2 Diabetes and another 20% to 50% of women with

gestational diabetes would have the chance of developing diabetes in the next 5 to 10

years. Since this research is only focusing on two main types of diabetes, further

discussion on the latter is not included (National Diabetes Fact Sheet United States,

2005).

1.1.5 Main Complications of Diabetes

Among the main complications of diabetes are heart disease and strokes (65% of deaths

in people with diabetes), high blood pressure (about 73%), blindness where diabetes is the

leading cause of new blind cases among adults aged 20 to 74 years old, kidney disease

(44% new cases), nervous system disease (60% to 70%), amputations (>60%), dental

disease, complication of pregnancy, biochemical imbalance and others. Type 1 and 2

Diabetes has different kinds of symptoms. In Type 1 Diabetes, the major symptoms are

frequent urination, unusual thirst, extreme hunger, unusual weight loss, extreme fatigue

and irritability. In Type 2 Diabetes, the major symptoms are any of the Type 1 Diabetes

6

symptoms, frequent infections, blurred vision, cutslbruises that are slow to heal,

tingling/numbness in the hands/feet and recurring gum, skin or bladder infections

(National Diabetes Fact Sheet United States, 2005).

1.2 Current Issues

As cited in the National Diabetes Fact Sheet (NDFS) from the Centers of Disease Control

(CDC), diabetes was the sixth major killer for mortality in term of health related field in

America in 2005 (Centers of Disease Control, 2006). Not only that, diabetes has not only

been identified as major health problem in the Western countries alone, it was also at the

forefront of the current epidemic of diabetes in Asia Pacific region too (Cockram, 2000).

According to that research, the prevalence rate of Type 1 and 2 Diabetes was on the rise

and that included Malaysia with an estimated of about 50 million of diabetic sufferers just

in China and India alone in 2025. According to World Health Organization (WHO), the

numbers of diabetic patients in Malaysia would tripled in 2030 with estimated patients of

about 2,479,000 from the 942,000 in 2000 (King, 2006). The main concern is the

increasing trend for Type 2 Diabetes particularly in young people. In children and

adolescents in some part of Asia Pacific region, Type 2 Diabetes now outnumbered Type

1 Diabetes by a ratio of 4:1. It was found that the diabetes was caused by many factors

such as the physical activities, lifestyle, diet and others. Now, most of the nations from

East to West are currently holding lots of international conferences and seminars on how

to curb this epidemic from rising. Listed below were the figures for the numbers of

diabetic patients in 2000 and the estimated numbers of diabetic patients in 2030. In the

7

India, 6 was for developed countries, 7 was for America and 8 was for other developing

countries which includes Malaysia. The value in the chart was in millions of people.

The Number of Diabetic Patients In 2000

87.78

9.82

Figure 1.1- The number of diabetic patients in 2000 (Yach et ai, 2006)

The &tIm.tad Number of Diabetic Patlants In 2030

200.2

Figure 1.2-The estimated number of diabetic patients in 2030 (Yach et ai, 2006)

8

1.2.1 Diabetes in the World

Diabetes was considered as one of the main global health issues in the world and the trend

of diabetic sufferer was currently showing a significant increase. According to Health

Department, the estimated number of people with diabetes will increase from 151 million

people in 2000 to about 221 million people in 2010. An increase of 70 million people was

equivalent to an increase of 46% within 10 years of time frame. Prediction compiled by

Dr Hillary King of the World Health Organization (WHO) indicated that this figure will

rise to 300 millions by the year 2025 (King, 2006).

1.2.2 Diabetes in Asia

In Asia, India and China were the countries with the highest rate of prevalence of

diabetes. These countries would be expected to continue their domination as the nation

that has the highest rate of prevalence of diabetes in 2025. Although the rate of increase

of diabetic patients in China was quite moderate, contributing 38 million of diabetic

patients from the world population, it was the other way round in India. It will contribute

about 58 million of diabetic patients from the population in term of diabetes prevalence.

The increase in term of prevalence of Type 2 Diabetes among children and young

teenagers in Japan were said to be related with obesity factor and historical roots. The

scenario happened in Hong Kong was due to changes in lifestyle, physical activity and

excessive intake of food that have high calories (Yach et ai, 2006).

UMS UNIV£RSITI MALAYSIA SABAH

9

1.2.3 Diabetes in Malaysia

Malaysia was classified as the fourth nation with the highest prevalence rate of diabetes

patients in Asia According to International Diabetes Institute. the number of diabetes

patients in Malaysia was expected to raise from 800.000 patients in 2002 to 1.3 million

patients in 2010. A National Survey that was conducted in 2000 also showed that the

prevalence of diabetes exceeds 7% of the adult population. Meanwhile. (Yach et al. 2006)

reported that overweight and obesity was long has been regarded as the main driver of

diabetes. In Malaysia. the percentage of obese males and females with body mass index

(BMI) > 30 was 1.6 and 6.8 respectively in 2002. This figure will rise to 1.7 and 11.0 in

2010 respectively. The table below showed the rate of adult obesity in 2002 and estimated

level in 2010 for selected countries.


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