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 Table of Contents

1.0 Introduction …………………………………………………………………………2

2.0 Pathophysiology of Type II Diabetes Mellitus with links to Madam Suba’s case
including the risk factors, the pathogenesis and possible complications of Type II
Diabetes Mellitus…………………………………….……………………………....4

3.0 Treatment options available for Type II Diabetes Mellitus for Madam
Suba………..9

4.0 The differences between Type I Diabetes Mellitus and Type II Diabetes
Mellitus……………………………………………………………………………..10

5.0 Reason Madam Suba’s blood glucose level is high on admission in

hospital……...11

6.0 Conclusion………………………………………………………………………….12
1.0 Introduction

The development of type 2 diabetes mellitus (T2DM), one of the most common
metabolic disorders in the world, is primarily caused by a combination of two main factors:
defective insulin secretion by pancreatic -cells and the inability of insulin-sensitive tissues to
respond to insulin. Type 2 diabetes mellitus (T2DM) is one of the most common metabolic
disorders in the world. Therefore, the molecular mechanisms involved in the production and
release of insulin, as well as the insulin response in tissues, need to be strictly regulated so
that the insulin release and action can precisely satisfy the demand placed on them by the
metabolic system. As a result, dysfunctions in any of the underlying systems might result in a
metabolic imbalance, which in turn contributes to the pathogenesis of type 2 diabetes.

According to the World Health Organization (WHO,2019), diabetes mellitus is a

metabolic condition that is both chronic and characterised by excessive levels of blood
glucose. Diabetes mellitus, when left untreated, can cause damage to the cardiovascular
system, eyes, kidneys, and nerves over time. Over 90% of instances of diabetes mellitus are
classified as type 2 diabetes, which is a condition characterised by insufficient insulin
secretion by pancreatic islet beta cells, tissue insulin resistance (IR), and an inadequate
compensatory insulin secretory response.

This is the primary indicator of type 2 diabetes. The global rise in obesity, sedentary
lifestyles, high calorie diets, and population ageing are the key drivers of the type 2 diabetes
epidemic. These factors have resulted in a fourfold increase in the incidence and prevalence
of type 2 diabetes.

The pancreas, liver, skeletal muscle, kidneys, brain, small intestine, and adipose tissue
are some of the organs that are implicated in the development of type 2 diabetes.
Inflammation, abnormalities in gut microbiota, immunological dysregulation, and
inflammation have emerged as major pathophysiological variables.

The epidemiological data show disturbing results that forecast a concerning

anticipated future for type 2 diabetes. The International Diabetes Federation (IDF) estimates
that diabetes will be responsible for 4.2 million deaths worldwide in 2019. As of 2019, there
were 463 million adults between the ages of 20 and 79 years old who were living with
diabetes; this number is expected to reach 700 million by the year 2045. (IDF,2019).

Individuals between the ages of 40 and 59 have diabetes at a rate that is three times
higher than any other age group. The incidence and prevalence of type 2 diabetes varies
according to geographical region. More than 80 percent of patients live in nations with low to
middle incomes, which presents extra obstacles in terms of appropriate treatment. Patients
diagnosed with type 2 diabetes mellitus have a 15 percent higher risk of death from any cause
when compared to people who do not have diabetes. (Zheng,2018) Cardiovascular disease
(CVD) is the leading cause of morbidity and mortality associated with type 2 diabetes.

The epidemiology of type 2 diabetes is influenced in equal measure by both genetics

and the environment. After being exposed to an environment that is defined by sedentary
behaviour and high-calorie intake, genetic factors begin to exhibit their effect on an
individual. Genome-wide association studies have found common glycaemic genetic
variations that are associated with type 2 diabetes. People of various racial and ethnic
backgrounds may have varying particular phenotypes that increase their vulnerability to
clusters of cardiovascular disease risk factors. These risk factors include insulin resistance,
hypertension, and dyslipidaemia. In this essay, we are going to discuss about :

i. The pathophysiology of Type II Diabetes Mellitus with links to Madam Suba’s

case including the risk factors, the pathogenesis and possible complications.
ii. Treatment options available for Type II Diabetes Mellitus for Madam Suba.
iii. The differences between Type I Diabetes Mellitus and Type II Diabetes
Mellitus.
iv. Madam Suba’s blood glucose level is high on admission in hospital

2.0. Pathophysiology of Type II Diabetes Mellitus with links to Madam Suba’s case
including the risk factors, the pathogenesis and possible complications of Type II Diabetes
Mellitus
2.1. Risk factors

There is a wide variety of risk factors for type 2 diabetes, including genetic,
metabolic, and environmental factors. These factors interact with one another, which
contributes to the disease's prevalence. Even though there is a strong genetic basis for an
individual's predisposition to type 2 diabetes due to non-modifiable risk factors (such as
ethnicity and family history/genetic predisposition), evidence from epidemiological studies
suggests that many cases of type 2 diabetes can be prevented by improving the main
modifiable risk factors (obesity, low physical activity and an unhealthy diet).

A tendency that is inherited plays a significant role in the likelihood of developing

type 2 diabetes. The majority of these loci increase the risk of type 2 diabetes through
primary effects on insulin secretion, while a minority of them act through reducing insulin
action. This complex polygenic nature of type 2 diabetes has been shown by several genome-
wide association studies of type 2 diabetes conducted over the past decade.

The biggest risk factor for type 2 diabetes is obesity, which is defined as a body mass
index (BMI) of 30 kg/m2 or more. Obesity is also linked to metabolic abnormalities that lead
to insulin resistance. There is a negative linear association between body mass index and the
age at which type 2 diabetes is diagnosed.

A sedentary lifestyle is another risk factor for type 2 diabetes. These studies showed a
reduction of 34 percent and 56 percent of developing type 2 diabetes in participants who
walked 2–3 hours a week or at least 40 minutes a week, respectively. Sedentary lifestyles are
a risk factor for type 2 diabetes. (Lai,2019)

There are three key advantages of engaging in physical activity with regard to the
postponement of the onset of type 2 diabetes. To begin, the contraction of skeletal muscle
cells causes an increase in the flow of blood into the muscle, which in turn increases the
amount of glucose that is taken in from the plasma. Second, regular exercise helps lower the
amount of fat that is stored within the abdominal cavity, which is a well-known risk factor
that contributes to the development of IR. Last but not least, research has revealed that
engaging in exercise of a moderate intensity might boost glucose uptake by forty percent. Not
only can physical activity enhance glucose uptake and insulin sensitivity, but it also has the
potential to alleviate or even reverse inflammation and oxidative stress, both of which are risk
factors for type 2 diabetes. (Lai,2019)

2.2. Pathophysiology

In terms of the biology of the condition, an excessively high level of glucose in the
blood is caused by a breakdown in the feedback loops between insulin action and insulin
secretion. Insulin secretion is lowered when beta cells are dysfunctional, which limits the
body's ability to maintain physiological glucose levels. On the other side, insulin resistance
causes an increase in glucose synthesis in the liver and a reduction in glucose uptake in
muscle, liver, and adipose tissue respectively. Even if both processes take place early in the
pathogenesis and contribute to the development of the disease, beta-cell malfunction is
typically more severe than IR. This is because beta-cells are responsible for the majority of
the insulin production in the body. On the other hand, hyperglycemia is increased when both
beta-cell failure and insulin resistance are present, which leads to the onset of type 2 diabetes.

Cellular integrity must be maintained, and the mechanisms and pathways implicated
in the physiology of beta cells must be subjected to stringent regulation in order to protect the
normal functioning of beta cells.

2.2.1. The Secretion of Insulin: Physiological and Dysfunctional Mechanisms Leading to

Type 2 Diabetes

β-cells are the cells that are responsible for the creation of insulin, which is initially
produced as pre-proinsulin. As part of the maturation process, pre-proinsulin goes through a
conformational change that is facilitated in the endoplasmic reticulum (ER) with the
assistance of a number of proteins. This leads to the production of proinsulin. Following this,
proinsulin is moved from the endoplasmic reticulum (ER) to the Golgi apparatus (GA), where
it enters immature secretory vesicles and is subsequently cleaved into C-peptide and insulin.
 Insulin, once it has reached its mature state, is kept in granules until the release of
insulin is activated. A response to high amounts of glucose is the primary stimulus that sets
off the release of insulin. It is important to keep in mind that in addition to hormones and
amino acids, fatty acids, and other fatty acids, fatty acids can also promote insulin release.

When circulation glucose levels rise, beta cells primarily take in glucose through
GLUT2. When glucose first enters the cell, glucose catabolism is triggered, leading to an
increase in the ratio of ATP to ADP found inside the cell. This, in turn, causes ATP-
dependent potassium channels in the plasma membrane to close. Ca2+ is able to enter the cell
as a result of this, which leads to the depolarization of the membrane and the opening of the
voltage-dependent Ca2+ channels. The increase in the concentration of Ca2+ inside the cell
causes the priming and fusing of secretory insulin-containing granules to the plasma
membrane, which ultimately leads to the release of insulin from the cell.

Additionally, Ca2+ signals can be amplified by RY receptors (RYR), and RY

receptors may play important roles in stimulus-insulin secretion coupling due to their
strategic locations within the cell and their ability to mediate Ca2+-induced Ca2+ release.
This is because RY receptors are strategically located within the cell, and they can release
Ca2+ in response to Ca2+ (CICR). When the channel is sensitised by messenger molecules
generated from the metabolism of nutrients or by the binding of ligands, RYR is responsible
for the amplification of Ca2+ signals. These signals are implicated in the amplification of
insulin secretion.

Nevertheless, the release of insulin from beta-cells can be assisted or enhanced by the
action of other cell signals. Among these messengers, cAMP is likely to play the most
significant role in stimulating the release of insulin. When stimulated by glucose, beta cells
release ATP through a process called exocytosis of insulin granules.

2.3 Complications

Diabetes type 2 is a multi-system disease that has a substantial link with the
development of cardiovascular disease. T2DM is associated with both micro- and macro-
vascular complications, the latter of which consists of accelerated atherosclerosis leading to
severe peripheral vascular disease, premature coronary artery disease (CAD), and increased
risk of cerebrovascular diseases.(Picke,2019) This leads to a two- to four-fold increase in the
mortality rate of adults from heart disease and stroke. T2DM also leads to an increase in the
number of people who develop type 2 diabetes. Because of these variables, type 2 diabetes is
regarded as a significant risk factor for cardiovascular disease. This is most likely due to the
participation of a number of different molecular mechanisms and pathological pathways.
Among these include the part that insulin receptor (IR) plays in atherosclerosis, vascular
function, oxidative stress, hypertension, the build-up of macrophages, and inflammation.

3.0 Treatment options available for Type II Diabetes Mellitus for Madam Suba

According to (Martinez,2019), the primary focus of early intervention should be on

behavioural modifications. In addition, alterations in one's way of life have been shown to be
beneficial, although maintaining these alterations over the long term can be difficult for many
patients due to differences in their experiences or views [8]. In general, pharmacological
therapy consists not only of initial hypoglycaemic agents but also of further intensification
methods to maintain glycaemic control over time. This requires the use of multiple
medicines, each of which must have a different mechanism of action [9]. It is important for
doctors to be knowledgeable with the various types of diabetes medications currently
available on the market so that they may select those that are the most effective, safe, and
well tolerated by their patients.

For Madam Suba, it has been suggested that the caloric intake of the food that is
recommended for a diabetic patient who is also obese should contain between 500 and 1000
kcal less than the patient's requirements for its essential source of energy. This weight loss
will result in an increase in insulin sensitivity, which is a positive aspect that will contribute
to an improvement in glycemic control parameters.

Metformin is considered to be the agent of first line treatment for the treatment of
type 2 diabetes, provided that there are no contraindications to its use. Metformin inhibits
gluconeogenesis through four main pathways. It brings about a roughly 20 percent reduction
in blood glucose levels when fasting and a 1.5 percent reduction in HbA1c. (Hussain,2019)

Both sulfonylureas and meglitinides or glinides, which are known as insulin

secretagogues, are different families of oral hypoglycaemic medications; nonetheless, they
share a similar mechanism of action in that they stimulate the release of insulin from
pancreatic beta cells.

GLP1 in humans is secreted in response to the consumption of food and increases the
release of insulin. Patients with type 2 diabetes who were treated with GLP1 had an increase
in the glucose-dependent secretion of insulin, a decrease in the secretion of glucagon, a
slowing of stomach emptying, an increase in satiety, and a reduction in food consumption.

Oral insulin is a relatively new therapy option for patients with type 2 diabetes that
aims to enhance glycemic control. Insulin taken orally has a greater physiological effect than
insulin given intravenously. When compared to insulin given parenterally, it lowers the risk
of hypoglycemia since it goes through the liver first. This decreases glycogenolysis as well as
hepatic glucose synthesis.

4.0 The differences between Type I Diabetes Mellitus and Type II Diabetes Mellitus.

Diabetes type 1, also known as insulin-dependent diabetes, is an autoimmune illness

in which the pancreas, which is the gland that produces insulin, begins to be destroyed by the
immune system. People who suffer from Type 1 diabetes may require multiple insulin
injections or a continuous insulin infusion throughout the day in order to maintain normal
levels of blood sugar. This is because the body is unable to produce its own insulin, so people
with Type 1 diabetes must take insulin in some other form. Although type 1 diabetes can
develop at any age, the majority of people who are afflicted with this form of the disease are
children, adolescents, and young adults. Regrettably, neither a treatment nor a method for
preventing this type of cancer exist; the condition can only be managed.

More than 80 percent of all cases of diabetes that are diagnosed in Malaysia are of the
type 2, also known as non-insulin diabetes. This form is the most frequent. Insulin is
produced by people with this type of diabetes, but the cells in their bodies either stop
responding to it the way they used to or grow resistant to the insulin that is produced by the
body itself. Diabetes type 2 is typically diagnosed in patients over the age of 40; however, it
can also manifest in young children. Diabetes type 2 can be effectively controlled or managed
if detected at an earlier stage and treated with a nutritious diet, weight loss, and regular
physical activity.
5.0 Reason Madam Suba’s blood glucose level is high on admission in hospital

Madam Suba was diagnosed with Type II Diabetes Mellitus with risk factors of
obesity and sedentary life style. With her condition and increased intake of sugary diet, her
body is not able to carry out the glycogenesis process with even there is high level of insulin
in her body. Thus she experienced hyperglycaemia upon admission to the hospital.

Hyperglycaemia is the result of the progression of the disease, which renders insulin
secretion unable to maintain the normal level of glucose in the blood. Patients who have type
2 diabetes are almost always obese or have a larger percentage of body fat are prone to have
excess glucose in the body due to failure of the glycogenesis process.

6.0. Conclusion

Research on this subject has to keep expanding since rising globalisation and the
normalisation of a sedentary lifestyle, combined with an increase in obesity, diabetes, and the
co-morbidities that result from these conditions, are all contributing factors. It is absolutely
necessary, in order to prevent, control, treat, or revert the pathophysiology of type 2 diabetes
and its complications, to have an understanding of the processes that are implicated at every
step in the development of the disease and its problems. Even though the early detection of
type 2 diabetes through screening and intensive patient-centered management helps to
optimise quality outcomes for patients, more research is required to define the causal factors
that account for correlations among various demographic subsets and the corresponding
variable risks for type 2 diabetes, as well as the drivers of increased risk in individuals with
low socioeconomic status.

New treatments should be implemented and treatments should be individualised and

targeted appropriately with the help of molecular genetic tools by identifying specific variants
contributing to disease development as well as by searching biomarkers to assess progression
and response to therapeutic interventions. This is because the pathophysiology and
underlying mechanisms of type 2 diabetes are becoming increasingly understood.
 Metformin and other lifestyle adjustments constitute the foundation of the initial care
of type 2 diabetes (T2DM). However, there is an increasing variety of second- and third-line
pharmacological medications that can be used to treat this illness. There are currently several
distinct medication families, both oral and injectable, that can be used for the treatment of
type 2 diabetes. Sulfonylureas, meglitinides, insulin, TZD, and alpha-glucosidase inhibitors
are some examples of these types of medications.

Additionally, insulin mimics that more accurately simulate the body's natural
production of insulin have been produced. Metformin continues to be the therapy of choice
for the vast majority of patients. Patient characteristics such as the degree of hyperglycaemia,
the presence of co-morbidities, and patient preference and ability to access treatments; and
properties of the treatment such as the effectiveness and durability of lowering blood glucose,
the risk of hypoglycaemia, the effectiveness in reducing diabetes complications, the effect on
body weight, side effects, and contraindications should be individualised when selecting
other alternative or second-line treatment options. Even while it does not appear that a cure
for diabetes will be developed in the near future, new safe and effective medications that will
improve the quality of life of T2DM patients should be developed.
6.0. References

Zheng, Y., Ley, S. H., & Hu, F. B. (2018). Global aetiology and epidemiology of type 2
diabetes mellitus and its complications. Nature reviews. Endocrinology, 14(2), 88–98.
https://doi.org/10.1038/nrendo.2017.151

Picke, A. K., Campbell, G., Napoli, N., Hofbauer, L. C., & Rauner, M. (2019). Update on the
impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocrine
connections, 8(3), R55–R70. https://doi.org/10.1530/EC-18-0456

Hussain, S., & Chowdhury, T. A. (2019). The Impact of Comorbidities on the

Pharmacological Management of Type 2 Diabetes Mellitus. Drugs, 79(3), 231–242.
https://doi.org/10.1007/s40265-019-1061-4

Martinez, L. C., Sherling, D., & Holley, A. (2019). The Screening and Prevention of Diabetes
Mellitus. Primary care, 46(1), 41–52. https://doi.org/10.1016/j.pop.2018.10.006

Lai, L. L., Wan Yusoff, W., Vethakkan, S. R., Nik Mustapha, N. R., Mahadeva, S., & Chan,
W. K. (2019). Screening for non-alcoholic fatty liver disease in patients with type 2 diabetes
mellitus using transient elastography. Journal of gastroenterology and hepatology, 34(8),
1396–1403. https://doi.org/10.1111/jgh.14577

Eckstein, M. L., Williams, D. M., O'Neil, L. K., Hayes, J., Stephens, J. W., & Bracken, R. M.
(2019). Physical exercise and non-insulin glucose-lowering therapies in the management of
Type 2 diabetes mellitus: a clinical review. Diabetic medicine : a journal of the British
Diabetic Association, 36(3), 349–358. https://doi.org/10.1111/dme.13865

Massey, C. N., Feig, E. H., Duque-Serrano, L., Wexler, D., Moskowitz, J. T., & Huffman, J.
C. (2019). Well-being interventions for individuals with diabetes: A systematic
review. Diabetes research and clinical practice, 147, 118–133.
https://doi.org/10.1016/j.diabres.2018.11.014
Chinese Diabetes Society, & National Offic for Primary Diabetes Care (2018). Zhonghua nei
ke za zhi, 57(12), 885–893. https://doi.org/10.3760/cma.j.issn.0578-1426.2018.12.003

Akalu, Y., & Birhan, A. (2020). Peripheral Arterial Disease and Its Associated Factors
among Type 2 Diabetes Mellitus Patients at Debre Tabor General Hospital, Northwest
Ethiopia. Journal of diabetes research, 2020, 9419413. https://doi.org/10.1155/2020/9419413
Part II
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