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UNIVERSITI PUTRA MALAYSIA
INSULINOTROPIC PROPERTIES OF SEVERAL MALAYSIAN HERBS AND GANODERMA SPECIES
MOHD SAUFI BASTAMI.
FBSB 2006 2
INSULINOTROPIC PROPERTIES OF SEVERAL MALAYSIAN HERBS AND GANODERMA SPECIES
BY
MOHD SAUFI BASTAMI
Thesis submitted to School of Graduate Studies, Universiti Putra Malaysia, in fulfilment of the Requirements for the Degree of Master of Science
January 2006
Abstract of thesis presented to the Senate of Universiti Putra Malaysia in f~dfilment of the requirement for the degree of Master of Science
INSULINOTROPIC PROPERTIES OF SEVERAL MALAYSIAN HERBS AND
GANODERMA SPECIES
BY
MOHD SAUFI BASTAMI
January 2006
Chairman : Muhajir Hamid, PhD
Faculty : Biotechnology and Biomolecular Sciences
Diabetes Mellitus incident is currently one of the major and common diseases in
Malaysia and increasing every year. To date, no herbs or drugs are able to completely
cure the disease. In this study, insulinotropic properties of Malaysian herbs were
investigated using pancreatic P cells BRIN-BD1 1 . Three out of 13 herbs samples studied
were belongs to fungi (Ganoderma sp). The studied showed seven samples are able to
induce insulin secretion over 200 % by BRIN-BD11 cell lines. Based on traditional
practitioner reports, Gynuraprocumbens was choosed for further investigation on its anti-
hyperglycemic properties. Glucose tolerance test were carried on normal and
streptozotocin-induced diabetic rats showed at 1000 mglkgl b.w Gynura procumbens
methanolic extract was able to reduce blood glucose level in rats. Toxicity towards
BRIN-BD11 cells was analyzed using MTT assay and alkaline comet assay. Toxicity
levels at ICS0 was 300 uglml using MTT assay. Furthermore, Alkaline Comet Assay has
proved this toxicity is not due to DNA damage in BRIN-BDl 1 cells. Acute toxicity was
carried on ICR strain mice for 14 days. Gynuraprocumbens did not show any toxicity at
concentration 7 glkg b.w after administered orally. These results suggest Gynura
procumbens and other herbs contain active constituents and have potentials for diabetes
treatment.
Abstrak tesis yang dikemukakan kepada Senat Universiti Putra Malaysia sebagai memenuhi keperluan untuk ijazah Master Sains
CIRI-CIIU INSULINOTROPIK BEBERAPA HERBA MALAYSIA DAN SPESIES
GANODERMA
Oleh
MOHD SAUFI BASTAMI
Januari 2006
Pengerusi : Muhajir Hamid, PhD
Fakulti : Bioteknologi dan Sains Biomolekul
Kes penyakit Diabetis Mellitus atau Kencing Manis kini menjadi penyakit utama
dihadapi oleh kebanyakkan pesakit manakala bilangannya semakin meningkat setiap
tahun di Malaysia. Sehingga kini masih belum ada ubat atau herba yang dapat
memulihkan daripada penyakit ini sepenuhnya. Dalam kajian ini, ciri-ciri insulinotropik
dari tumbuhan herba Malaysia di jalankan bagi melihat kebolehan tumbuhan herba
merangsang penghasilan insulin oleh sel selanjar model sel P pankreas BRIN-BDll.
Sejumlah tiga dari 13 sampel yang di kaji terdiri dari golongan kulat (Ganoderma sp).
Kajian mendapati tujuh daripada sample kajian berupaya merangsang penghasilan insulin
lebih dari 200 % oleh sel BRIN-BD1 1. Gynura procumbens dipilih berdasarkan laporan
pengamal perubatann tradisional untuk ujian lanjut ciri-ciri anti hyperglycemia.
Seterusnya, kajian toleransi glukosa ekstrak methanol Gynura procumbens terhadap tikus
normal dan tikus diabetik yang di aruh oleh streptozotocin mendapati 1000 mglkg b.w
ekstrak berupaya menurunkan paras glukosa darah. Kajian toksisiti terhadap sel BRIN-
BDl l mengunakan asai MTT dan Asai Komet Beralkali dijalankan. Asai MTT
memberikan keputusan paras toksisiti Gynura procumbens pada ICso adalah 300 uglml.
Walaubagaimanapun, Asai Komet Beralkali membuktikan toksisiti ini berlaku bukan
disebabkan oleh pemusnahan DNA di dalam sel BRIN-BD11. Tahap toksisiti akut
dijalankan kepada mencit dari strain ICR untuk tempoh 14 hari. Gynura procumbens
didapati tidak memberi kesan toksik pada kepekatan 7 glkg b.w selepas ekstrak di
masukkan secara oral. Keputusan ini menunjukkan Gynura procumbens dan tumbuhan
herba yang lain mengandungi komponen aktif dan berpotensi dalam rawatan kencing
manis.
ACKNOWLEDGEMENTS
I would like to express my sincere thanks and appreciation to my supervisor Dr. Muhajir
Hamid for his advice, support, encouragement and his patience. I am especially grateful
to him for his intellectual guidance and constructive comments throughout the course of
this study and during the preparation of the manuscript and for being so freely available
at all stages for discussion.
Sincere appreciations are extended to my supervisory committee, Prof Dr. Abd. Manaf
Ali and Associate Prof Dr. Khozirah Shaari for their advice and support throughout the
past years and for imparting valuable knowledge. Without their help, this study could not
be completed successfully.
Many thanks are also due to my lab mates, Pn. Nazrien Kaman, Ms. Siti Pauliena Bohari
and Mr. Tajul Anuar which giving support and sharing their time during the previous
studies which help on numerous improvements. An acknowledgement is due to En.
Hussain Jiragon on helping me on providing materials needed and not forgotten to Ms.
Hairiah Yunus for all the guidance and support on completing this thesis.
My special thanks also goes to Head Department of Microbiology, Faculty of
Biotechnology and Biomolecular Sciences, Associate Prof. Dr Raja Noor Zaliha and to
all staff at the department.
To the Graduate School Office of Universiti Putra Malaysia, grateful acknowledged for
providing me with a Master Science studentship to perform this research.
Finally, sincere thanks are fondly expressed to my family and my beloved wife Noazira
Idris for their love, patience and support throughout this work. You never know how
much I appreciate it - a big thank you.
I certify that an Examination Committee met on 13'" Febuary 2006 to conduct the final examination of Mohd Saufi Bastami on his Master of Science thesis entitled "Insulinotropic Properties of Several Malaysian Herbs and Ganoderma Species" in accordance with Universiti Putra Malaysia (Higher Degree) Act 1980 and Universiti Putra Malaysia (Higher Degree) Regulations 198 1. The committee recommends that the candidate be awarded the relevant degree. Members of the Examination Committee are as follows:
Johari Ramli, PhD Associate Professor Faculty of Biotechnology and Biomolecules Science Universiti Putra Malaysia (Chairman)
Mohd Noor Abd. Wahab, PhD Associate Professor Faculty of Biotechnology and Biomolecules Science Universiti Putra Malaysia (Internal Examiner)
Amin Ismail, PhD Lecturer Faculty of Medicine and Health Sciences Universiti Putra Malaysia (Internal Examiner)
Jamaludin Hj Mohamed, PhD Professor, Faculty of Allied Health Sciences Universiti Kebangsaan Malaysia (External Examiner)
School of Graduate Studies Universiti Putra Malaysia
Date :
vii
This thesis submitted to Senate of Universiti Putra Malaysia has been accepted as fulfillment of the requirement for the degree of Master of Science. The members of the Supervisory Committee are as follows:
MUHAJIR HAMID, PhD Lecturer Faculty of Biotechnology and Biomolecular Sciences Universiti Putra Malaysia (Chairman)
ABDUL MANAF ALI, PhD Professor, Faculty of Biotechnology and Biomolecular Sciences Universiti Putra Malaysia (Member)
KHOZIRAH SHAARI, PhD Associate Professor Faculty of Science Universiti Putra Malaysia (Member)
AINI IDERIS, PhD ProfessorIDean School of Graduate Studies Universiti Putra Malaysia
. . . V l l l
DECLARATION
I hereby declare that the thesis is based on my original work except for quotations and citations which have been duly acknowledged. I also declare that is has not been previously or concurrently submitted for any other degree at UPM or other institutions.
Date:
TABLE OF CONTENTS
Page
DEDICATION ABSTRACT ABSTRAK ACKNOWLEDGEMENTS APPROVAL SHEETS DECLARATION TABLES OF CONTENTS LIST OF FIGURES LIST OF TABLES ABBREVIATION
CHAPTER
1 INTRODUCTION
1 . . 11 . . . 111
iv vii 1X
X
xii xv xvi
LITERATURE REVIEW 5 2.1 Diabetes Mellitus 5
2.1.1 Types of Diabetes 6 2.1.2 Type 1 : Insulin -Dependent Diabetes Mellitus 6 2.1.3 Type 2 : Non-Insulin Dependent Diabetes Mellitus 7 2.1.4 Other Types of Diabetes 2.1.5 Complications of Diabetes 2.1.6 Diabetes and Its Impact Insulin 2.2.1 Insulin Synthesis and Characteristic 2.2.2 Insulin Mechanism and Action 2.2.3 Other Usage of Insulin Treatment Strategies For Diabetes 2.3.1 Insulin Injection 1 Replacement 2.3.2 Pancreas or Islet Transplantation in Diabetes 2.3.3 Diet Control on Diabetic Patient 2.3.4 Commonly Used Drugs on Diabetes Treatment Medicinal Plants As Alternative Disease Treatments Insulin Secreting Cell Lines
MATERIALS AND METHODS 3.1 Plant Samples 3.2 Animals 3.3 Plants Sample Extraction 3.4 BIUN-BD 1 1 Cells Culture Passage
Cytotoxicity Assay Towards Plants And Ganoderma Samples 28 Insulin Release Activity From Insulin Secreting Cell Lines 30 Rat Insulin Elisa Assay 3 1 Streptozotocin Induce Diabetic Rats 3 1 Oral Glucose Tolerance Test By Gynura Procumbens Methanol Extract 3 2 The SCGE / Comet Assay 3 3 BRIN-BDI 1 Cells Morphological Examination By AOPI Assay 34 Acute Toxicity Study Of Gynura Procumbens Methanol Extract Towards ICR Mice 3 5 Statistical Analysis 3 5
RESULTS AND DISCUSSION Cytotoxicity Effects of Plants And Ganoderma Samples Towards BRIN-BD 1 1 Cells 3 6 Insulin Secretion Responses on Malaysian Traditional Plants. 3 9 Insulin Secretion Response by Ganoderma Species. 6 8 Insulinotropic Properties of Malaysian Herbs As Alternative In Diabetes Treatment. 74 Comparison Between Glybenclamide, Tolbutamide And Plants Sample On Percentage Insulin Release. 8 0 Oral Glucose Tolerance Test On Gynura Procumbens. 8 4 In Vitro Cytotoxicity Study (MTT Assay) Of BRIN-BD1 1 Cells Treated By Gynura Procumbens 89 Single Cells Electrophoresis Assay (Comet Assay) of Gynura Procumbens Extract On BRIN-BD 1 1 Cells 9 1 Morphological Examination of BRIN-BD 1 1 Cells By AOPI Assay 93 Acute Toxicity Study of Gynura Procumbens Extract On ICR Mice 97
CONCLUSION
REFERENCES APPENDIX BIODATA OF THE AUTHOR
LIST OF FIGURES
Figure
2.1 Human insulin amino acids sequences on chain A and chain B
3.1 Morphology of BRIN-BD1 1 cells as assessed by phase contrast microscopy (X 200 magnification.)
4.1 The effect of Glybenclamide drugs on insulin secretion by BRIN- BDl 1 cell lines after 30 minutes incubation.
4.2 Percentage insulin release by BRIN-BDll cell lines compared to control after 30 minutes treatment with Glybenclamide.
4.3 The effect of Tolbutamide drugs on insulin secretion by BRIN-BDl 1 cell lines after 30 minutes incubation.
4.4 Percentage insulin release by BRIN-BDl1 cell lines compared to control after 30 minutes treatment with Tolbutamide.
4.5 The effect of A.paniculata methanol extract on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.6 Percentage insulin release by BRIN-BD11 cell lines compared to control after 30 minutes treatment with A.paniculata.
4.7 The effect of different A.paniculata fractions on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.8 The effect of F.deltodia methanol extract on insulin secretion by BRIN-BD 1 1 cell lines after 30 minutes incubation.
4.9 Percentage insulin release by BRIN-BDl1 cell lines compared to control after 30 minutes treatment with F. deltodia methanol extract.
4.10 The effect of Gynura procumbens methanol extract on insulin secretion by BRIN-BD 1 1 cell lines after 30 minutes incubation.
4.1 1 Percentage insulin release by BRIN-BDll cell lines compared to control after 30 minutes treatment with G.procumbens methanol extract.
4.12 The effect of Labisia pumila methanol extract on insulin secretion by BRIN-BDl 1 cell lines after 30 minutes incubation.
Page
11
2 9
xii
4.13 Percentage insulin release by BRIN-BD1 1 cell lines compared to control after 30 minutes treatment with L.pumila methanol extract.
4.14 The effect of Momordica charantia methanol extract on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.15 Percentage insulin release by BRIN-BD11 cell lines compared to control after 30 minutes treatment with Momordica charantia methanol extract.
4.16 The effect of Morinda citrifolia methanol extract on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.17 Percentage insulin release by BRIN-BDl 1 cell lines compared to control after 30 minutes treatment with Morinda citrifolia methanol extract.
4.18 The effect of Orthosiphon spicatus methanol extract on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.19 Percentage insulin release by BRIN-BD11 cell lines compared to control after 30 minutes treatment with Orthosiphon spicatus methanol extract.
4.20 The effect of Tinospora cripsa methanol extract on insulin secretion by BRlN-BD1 1 cell lines after 30 minutes incubation.
4.21 Percentage insulin release by BRIN-BD11 cell lines compared to control after 30 minutes treatment with Tinospora crispa methanol extract.
4.22 The effect of Zingiber officinale methanol extract on insulin secretion by BRIN-BDl I cell lines after 30 minutes incubation.
4.23 Percentage insulin release by BRIN-BDll cell lines compared to control after 30 minutes treatment with Zingiber ofJicinale methanol extract.
4.24 The effect of Phylantus nirruri methanol extract on insulin secretion by BRIN-BD1 1 cell lines after 30 minutes incubation.
4.25 The effect of G.lucidum extract on insulin secretion by BRIN-BD11 cell lines after 30 minutes incubation.
... X l l l
4.26 The effect of G.tropicum extract on insulin secretion by BRIN-BDl 1 cell lines after 30 minutes incubation.
4.27 The effect of G.tsugae extract on insulin secretion by BRIN-BD11 cell lines after 30 minutes incubation.
4.28 Percentage insulin release by BRIN-BDI 1 cell lines compared to control after 30 minutes treatment with various species of Ganodenna extract.
4.29 The effect of G.procumbens methanol extract leaves on oral glucose tolerance test (OGTT) in normal rats
4.30 The effect of G.procumbens methanol extract leaves on oral glucose tolerance test (OGTT) in diabetic rats
4.31 The effect of Gynura procumbens methanol extract on percentage relative viability of BRIN-BD1 1 cells line.
4.32 SCGE of BRIN-BDI 1 after treatment with Gynura procumbens methanol extract.
4.33 BRIN-BDI 1 cells processed in the comet assay. Image of target cells DNA after micro electrophoresis below fluorescent microscope.
xiv
LIST OF TABLES
Table
2.1 An insulin amino acids sequence in vertebrates.
3.1 List of plants used in the experiment, source, part used and their local name.
4.1 Inhibition concentration 50 % (ICSo) of Malaysians herbs and Ganoderma sp. on BRIN-BDl 1 cells by cytotoxicity assay compared to tolbutamide drugs.
4.2 Comparison percentages of insulin released between glybenclamide and tolbutamide.
4.3 Potentiating activity of insulin-secretory activity by methanol extract and drugs
4.4 Morphological examination of BRIN-BD1 1 cells by AOPI assay
4.5 Acute toxicity study of Gynuraprocumbens methanol extract on ICR mice
Page
13
25
cmL
DMSO
DNA
"C
EDTA
ELISA
EtBr
FBS
g
IC50
KRBB
LMA
M
mA
ml
mM
MTT
N
NaCl
NMA
nrn
OGTT
PBS
RPMI 1640
W
LIST OF ABBREVIATIONS
Body weight
Carbon dioxide
Centimeter square
Dimethyl sulfoxide
Deoxyribonucleic Acid
Degree Celsius
Ethylenediamine tetraacetic acid
Enzyme-Linked Immunosorbent Assay
Ethidium Bromide
Feotal bovine serum
Gram
Concentration of 50% inhibitory
Krebs Ringer bicarbonate buffer
Low melting agarose
Molar
mili Ampere
Milliliter
milimolar
3-[4,5-dimetiltiazol-2-yl]-2,5-dimetiltetrazolium
bromide
Normality
Sodium Chloride
Normal melting agarose
Nanometer
Oral glucose tolerance test
Phosphate buffer saline
Roswell Park Memorial Institute 1640 Medium
Watt
xvi
v/v
ul
mg
w/v
mmol
Volume /volume
Microliter
Miligram
Weight / volume
Milimole
xvii
CHAPTER 1
INTRODUCTION
Herbal and natural products have been used for centuries throughout the world in every
culture especially on disease treatments by traditional method. Traditional medicines are
medicine is made from natural resources whether plant, fauna or mineral. It can be found
throughout the world either in the water or land. Malaysia is known for its diversity
which are claimed to possess medicinal value. The Malaysians also practice traditional
and herbal remedies as an alternative choice for disease treatment. Traditional medicines
are still a source of disease treatment of the world population. It has been shown by
Phillipson and Wright that 80 % of the world populations depends on traditional
medicine (Rahrnan et al., 1999). In two separate surveys recently conducted in Australia
and United States respectively that almost 48.5 % and 34 % of respondent have used at
least one form of unconventional therapy including herbal medicine (Grover et al., 2001).
Furthermore, many of the current commercial drugs are derived from traditional plants
based. In the United States, approximately 25 % of prescription contains active
ingredients derived from plants. However the proportion in others countries are varies,
such as in Germany, 40 % of drugs are based on plant materials (Lee, 1999). Well
known drug for headache, aspirin, was originally created from two herbs, - white willow
bark and meadowsweet (Lee, 1999). Traditional herbs were also generating an economic
value to some countries in the world on medicinal aspect. About 30 % of the worldwide
sales of drugs are based on natural product or herbs. Developing new potential drugs
might cost millions dollars. Pharmaceutical companies have to spend IJS$ 350 million
dollars to develop new drugs (Grabley & Thiericke, 1999).
Malaysian herbal market is valued at about US$ 20 billion and growing at a rate of 20 %
annually. Much of it is imported either from Indonesia, China or India (Kadir & Lope
Pihie, 2001). Malaysian herbal research and development are focusing into few herbs
discoveries such as anti-malarial, cytotoxicity, anticancer agents from Goniothalamus
and male aphrodisiacs agent from the root extract of Eurycoma lingofolia (Kadir &
Shaari, 2000). There are many more potential herbs which were used by traditional
practitioner which are undiscovered.
Noor and Ashcroft (1989) described that over the past years; scientific and medical
knowledge on the role of plant-derived product in the treatment of diabetes mellitus has
advanced and created an exciting new area of research which could provide valuable
information for the development of alternative drugs. With rich of natural resources,
almost 6800 species of seed plants and 600 seedless plants, Malaysia may able to develop
drugs towards many diseases.
Most studies on remedies usage are not really understood. Scientific studies have been
carried out on several plants which believed to possess anti-diabetic properties.
Andrographis paniculata, the king of bitter is used since immemorial times as Chinese
and Ayuverdic medicine mainly for liver disease and dysentery was combined with
Orthosiphon spicatus on diabetes treatment (Akowuah et al., 2004). In India,
hypoglycaemic activity of Momordica charantia or bitter gourd, known as 'peria katak'
in Malaysia, was studied since 1981 by Virdi et al., (2003). Meanwhile, Gynura
procumbens, found in various part of Southeast Asia, has been used for the treatment of
eruptive fevers, rash and kidney disease (Zhang & Tan, 2000). Other potential herbs
reported to have anti hyperglycaemic activity are Alium cepa, Allium sativum, Murraya
koeinigii, Viscum album, Sumbucus nigra, Tinospora crispa and Morinda citrifolia
(Grover et al., 2002). Most of these plants are easily found in Malaysia.
Development for potential drugs on diabetes treatments are not limited to plants, but also
able to be produced from Ganodenna. Ganoderma lucidum which known as 'Ling Zhi '
in China or 'reishi' in Japan was studied by Tomoda et al., (1986), is reported to have
hypoglycaemic activity. It is also deemed as an elixir of life that could augment good
health and well-being. However, hypoglycaemic activity and medicinal value of
Ganoderma tropicum and Ganoderma tsugae are unknown.
About 1200 species of Malaysian plants have been reported to have medicinal value.
Phytochemical screening, which aimed at scoring the presence of different types of
chemical compounds such as alkaloids, flavonoids, saponins, terpenoids, eugenols,
polyphenols, sterols, tannins, aloin, plysacharides, diterpenes and glycosides have been
carried out (Kadir and Shaari, 2000; Grover et al., 2002). These phytochemical
compounds have been reported to have anti-tumor, anti-oxidant also male and women
aprodiasiac properties (Kadir and Shaari, 2000). It is also believed to have potential on
enhancing insulin secretion from pancreatic cells since some Malaysian herbs were
used by traditional practioner on diabetes treatment.
The main objectives of the experiment are to study insulinothropic properties of some
Malaysian Herbs including some species of Ganoderma. Plants that have potential on
diabetes treatment as reported by traditional practioner will be used for insulinotrophic
acting using rat pancreatic p cell lines. Measurement was carried on insulin secreting cell
lines (BRIN-BDII cell lines) using insulin ELISA methods. Various insulin
concentrations are released by BRIN- BDl 1 cell lines affect from its stimulator. Plants
and Ganoderma samples was extracted and tested towards BRIN-BDI 1 cells on their
ability in enhancing insulin secretion and determine the cytotoxicity level and value
by [3-(4, 5-dimethylthiazol-2-y1)-2, 5-dimethyltetrazolium bromide (MTT) assay.
The second objective is to study the anti-hyperglycemic properties of Gynura
procumbens. A further study of Gynura procumbens methanolic extract on
hypoglycaemic activities and its toxicity was carried as Gynura procumbens was reported
by traditional practitioner to be safe taken as edible and useful in controlling diabetes.
Study were carried to determine the maximum insulin levels secreted by BRIN-BDI 1 cell
lines and in vivo study of OGTT (oral glucose tolerance test) on normal and induced
diabetic rats by Gynura procumbens methanolic extract. Toxicity level of Gynura
procumbens methanolic extract towards BRIN-BDl I cell lines and ICR strain mice will
be evaluated. The genotoxicity towards BRIN-BDl 1 also were studied by Comet Assay
and AOPI assay.
CHAPTER 2
LITERATURE REVIEW
2.1 Diabetes Mellitus
Diabetes mellitus (DM) is a complex disorder of carbohydrate, fat and protein
metabolism. It is primarily a result of a defect in secretion or action of insulin, the
hormone that facilitates and control the use of glucose in the cells. Due to the deficiency
of insulin, diabetic patients have an impaired tolerance to glucose that leads to numbers
of short term and long term complications. Early diagnosis of diabetes is determined by
blood glucose level. Glucose levels before meal are generally run between 4-7 mmolll or
60-100 mgldl in normal people (Williams & Porte, 1974; Dagget, 1981). Diabetes not
only limited to human being but also occurred on canine especially on type 1 diabetes,
insulin dependent diabetis mellitus (IDDM) (Davison et al., 2002).
Diabetes Mellitus is the commonest endocrine disorder that affects more than 100 million
people worldwide (6 % of the population) and projected to grow over 220 millions within
40-50 years (Proietto et al., 1999). In next 10 years, diabetes may affect about five times
more people than it does now (Bailey, 2000; Grover et al., 2002). Diabetes derived
fiom Greek for siphon, which refers to the copious excretion of water that characterizes
the disease, meanwhile mellitus came fiom Latin word for honey, characterized by the
high sugar content in urine.
In Malaysia, diabetes mellitus is increasing towards serious level. The Ministry of Health
has recorded 657,988 people in Malaysia suffering from diabetes in 2002 increasing from
525,858 in year 2001 (Abdullah, 2003). The number of diabetics estimated to be
increased to 0.8 million cases in 2025. From the reports of admissions to government
hospitals in Peninsular Malaysia, diabetes mellitus had increased from 5024 cases in
1979 to 17808 cases in year 1990, and in year 2020 about 144 600 Malaysians will
suffering diabetes (Amos et al., 1997).
2.1.1 Types of Diabetes
Diabetes can be divided into three distinct types, in which subtypes have been identified.
2.1.2 Type 1: Insulin -Dependent Diabetes Mellitus (IDDM)
Type 1 or insulin-dependant diabetes mellitus (IDDM) occurs in approximately 10 % of
all diabetics' patients in western world. The symptoms are hyperglycaemia due to
secondary insulin deficiency, occurring as a result of autoimmune destruction of
pancreatic endocrine p cells (Perfetti & Ahmad, 2000). Type 1 commonly occurs on
childhood (Docherty, 2001). This type of diabetes accounts for 3 % of all diabetes
worldwide in 1997, meanwhile type 2 is by far the most common type (Proietto et al.,
1999).
2.1.3 Type 2: Non-Insulin Dependent Diabetes Mellitus (NIDDM)
Non-insulin dependent diabetes mellitus occurs when insulin is no longer reacting as
metabolic hormone in reducing blood sugar level (insulin resistant) or insufficient ability
to secrete insulin (Proietto et al., 1999; Perfetti & Ahrnad, 2000). It is reported that type
2 diabetes has strong genetic tendency (Proietto et al., 1999). Combination of insulin
resistant and insufficient insulin released has accounting 90-95% of diabetes in developed
countries (Husen et al., 2004). About 90 % of diabetics in western world are categorized
by type 2 rather than type 1. Type 2 diabetic shows direct contact with obesity. Hartz et
al., 1983 and Kissebah et al., 1984, reports that a close relationship between upper body
obesity with type 2 diabetes by increased free fatty acid oxidation could impair glucose
oxidation thus leading to insulin resistance (Proietto et al., 1999). The risk of diabetes
seems to be increased ten times in women with both severe obesity and high waist to hips
ratio.
2.1.4 Other Types of Diabetes
Other types of diabetes including entities secondary to or associated with certain other
conditions or syndromes. Diabetes may be secondary to pancreatic disease removal of
pancreatic tissues, endocrine disease such as acromegaly, Cushing's syndrome,
glucagonoma, somatostatinoma, or the administration of certain drugs, hormones or
chemicals that causing hyperglycaemia (Hamid, 1999).
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