ASSIGNMENT

DIABETES MELLITUS

SUBMITTED TO:

SUBMITTED BY:

ASHIM BORAH SIR

NITASHA (Group-3)
RAJAT
PEEYUSH
ASHISH
VIVEK

INTRODUCTION

In 2013, it was established that over 382 million people throughout the world had diabetes.
It is a metabolic disease in which the person has high blood glucose, either because insulin
production is inadequate or because the bodys cells do not respond properly or both.

INSULIN
Insulin is a hormone. It makes our bodys cell absorb glucose from the blood. The glucose is
stored in the liver and muscle as glycogen and stops the body from using fat as a source of
energy.
Glucose level is maintained in the body by the appropriate levels of insulin and glucagon. The
pancreas releases glucagon when the concentration of glucose in the bloodstream falls too low.
Glucagon causes the liver to convert stored glycogen into glucose to be taken up and used by the
insulin dependent tissues.

Diagram showing balance between insulin and glucagon

TYPES OF DIABETES

1. TYPE 1
Pancreas does not produce insulin. This type of diabetes also referred to as insulin dependent
diabetes or early onset diabetes. People usually develop type 1 diabetes before adulthood or
teenage years. Approximately 10 percent of cases are type1.
CAUSE AND RISK FACTORS

Type1 diabetes is caused by a lack of insulin due to the destruction of insulin producing
beta cells in the pancreas i.e. it is an autoimmune disease. Beta cell destruction may take
place over several years, but the symptoms of the disease usually develop over a short
period of time.
GENETIC SUSCEPTIBILITY
Certain gene variants that carry instructions for making proteins called human leukocyte
antigens (HLA) on the white blood cells (WBCS) are linked to the risk of developing
type 1 diabetes.

The proteins produced by HLA genes help determine whether the immune system recognise a
cell as a part of the body or as foreign material. Some combinations of HLA gene variants predict
that a person will be at higher risk for type 1 diabetes. Many additional gene regions have been
found which help identify people at risk type1.
Genetic testing can show what types of HLA genes a person carries and can reveal other genes
related to diabetes.

ENVIRONMENTAL FACTORS
Environmental factors such as food, viruses and toxins may play a role in the
development of the type 1 diabetes, but the exact nature of their role has not been
determined.

2.TYPE 2
The body does not produce enough insulin for proper function or the cells do not interact with
the insulin in comprehensive manner (insulin resistance).
Approximately 90 percent of the cases worldwide are of this type 2. It a progressive disease.

CAUSE AND RISK FACTORS

Overweight and obese people have much higher risk of developing type2 diabetes. Being
obese causes the body to release chemicals that can destabilise the bodys cardiovascular
and metabolic systems.
Physical inactivity and age
GENETIC SUSCEPTIBILITY
The role of genes is suggested by the high rate of type2 diabetes in families and identical
twins and wide variations in diabetes prevalence by ethnicity. Type2 occurs more
frequently in African Americans, Alaska natives, American Indians etc.
Studies have shown that variants of the TCF7L2 gene increases susceptibility of type2
diabetes. For people who inherit two copies of the variants, the risk of developing type2
diabetes is about 80 percent higher than for those who do not carry the gene variant.

3. GESTATIONAL DIABETES
This type affects females during pregnancy. Some women have very high levels of
glucose in their bodies as they are unable to produce enough insulin to transport all of the
glucose into their cells, resulting in the progressively rising levels of glucose.
CAUSE AND RISK FACTORS

It is caused by the hormonal changes and metabolic demands of pregnancy together

with genetic and environmental factors.
Insulin resistance and beta cell dysfunction hormones produced by the placenta and other
pregnancy related factors contribute to insulin resistance which occurs in most of
pregnancy cases during late pregnancy.

Common symptoms of diabetes include:

Excessive thirst and appetite

Increased urination (sometimes as often as every hour)

Unusual weight loss or gain
Fatigue
Nausea, perhaps vomiting
Blurred vision
In women, frequent vaginal infections
In men and women, yeast infections
Dry mouth
Slow-healing sores or cuts
Itching skin, especially in the groin or vaginal area

Sexual and urological problems of diabetes facts

Sexual and urologic complications of diabetes occur because of the damage diabetes can
cause to blood vessels and nerves.
People with diabetes may experience bladder problems such as overactive bladder, poor
control of sphincter muscles that surround the urethra, urine retention, and urinary tract
infections.
Those people with diabetes who are at risk of sexual or urologic problems include people
who have poor glucose and blood pressure control; have high levels of cholesterol; are
overweight, are over the age of 40 years, those that smoke, and lack of physical activity.

Bladder Problems
Many events or conditions can damage nerves that control bladder function, including diabetes
and other diseases, injuries, and infections. More than half of men and women with diabetes have
bladder dysfunction because of damage to nerves that control bladder function. Bladder
dysfunction can have a profound effect on a person's quality of life. Common bladder problems
in men and women with diabetes include the following:

Overactive bladder: Damaged nerves may send signals to the bladder at the wrong time,
causing its muscles to squeeze without warning. The symptoms of overactive bladder include

urinary frequency-urination eight or more times a day or two or more times a night
urinary urgency-the sudden, strong need to urinate immediately

urge incontinence-leakage of urine that follows a sudden, strong urge to urinate

Poor control of sphincter muscles Sphincter muscles surround the urethra-the tube that carries
urine from the bladder to the outside of the body-and keep it closed to hold urine in the bladder.
If the nerves to the sphincter muscles are damaged, the muscles may become loose and allow
leakage or stay tight when a person is trying to release urine.
Urine retention: For some people, nerve damage keeps their bladder muscles from getting the
message that it is time to urinate or makes the muscles too weak to completely empty the
bladder. If the bladder becomes too full, urine may back up and the increasing pressure may
damage the kidneys. If urine remains in the body too long, an infection can develop in the
kidneys or bladder. Urine retention may also lead to overflow incontinence-leakage of urine
when the bladder is full and does not empty properly.

Tests to Diagnose Diabetes

1. Fasting plasma Glucose test (FPG)
2. Oral Glucose tolerance test (OGTT)

In FPG amount of glucose in the blood is taken after overnight fast (not eating for at least 8
hours).
In OGTT a person glucose level is measured after fasting and 2 hours drinking glucose rich
beverage than check blood glucose level.

After confirmation of Diabetes there are two tests which will check regular for controlling
diabetes
1. A1C Test: The A1C test can be used to diagnose type 2 diabetes and pre diabetes alone or
in combination with other diabetes tests. When the A1C test is used for diagnosis, the
blood sample must be sent to a laboratory that uses an NGSP-certified method for
analysis to ensure the results are standardized. Blood samples analyzed in a health care
providers office, known as point-of-care (POC) tests, are not standardized for diagnosing
diabetes. The following table provides the percentages that indicate diagnoses of normal,
diabetes, and pre diabetes according to A1C levels.

Having pre diabetes is a risk factor for getting type 2 diabetes. People with pre diabetes may be
retested each year. Within the pre-diabetes A1C range of 5.7 to 6.4 percent, the higher the A1C,
the greater the risk of diabetes. Those with pre diabetes are likely to develop type2 diabetes
within 10 years, but they can take steps to prevent or delay diabetes.

2.

Self-Monitoring of Blood Glucose (SMBG)

Self-monitoring of blood glucose or SMBG refers to home blood glucose testing for people with
diabetes. Self-monitoring is the use of regular blood testing to understand ones diabetes control
and inform changes to improve ones control or wider regime. Self-monitoring of blood glucose
levels has been a hotly disputed issue for a number of years, particularly with regards to people
with type 2 diabetes who are not on insulin.

Treatment and Drug:

Diabetes is a group of metabolic disease in which a person has high blood glucose .there are
three types of diabetes Type 1, Type2 & Gestational.
Type 1- There is no production of insulin.
Type 2- There is not enough production of insulin for proper function or the cells in the body do
not react to insulin (insulin resistance)
Gestational -This type of diabetes, which causes high blood sugar, develops during pregnancy
(gestation) and is caused by increased production of hormones that make the body less able to
use insulin as well as it should. Most gestational diabetes goes away after birth but it does put
you at higher risk of developing type2 diabetes later. Healthy eating and being active may
decrease the risk of developing subsequent type 2 diabetes.
Treatment for type 1 diabetes includes:

Taking insulin
Carbohydrate counting
Frequent blood sugar monitoring
Eating healthy foods
Exercising regularly and maintaining a healthy weight

Management of type 2 diabetes includes:

Healthy eating
Regular exercise
Possibly, diabetes medication or insulin therapy
Blood sugar monitoring

These steps will help keep your blood sugar level closer to normal, which can delay or prevent
complications.

DRUGS
Drug Name

Working mechanism

Metformin

Improving the sensitivity your

body to insulin so that body uses
insulin more effectively

Possible side effect

It does not lower the

blood sugar itself.
Nausea
Diarrhea

Sulfonylurease
Glyburide
Glipizide

Help your body to secrete more

insulin

Low blood sugar

Weight gain

Thaizolidines *

Like metformin more sensitive to

insulin

Heart failure
Fractures

* Because of the side effect of Thaizolidines, generally are not first choice of treatment.
Insulin therapy:
Some people who have Type 2 diabetes need insulin therapy as well .In past insulin therapy was
used as last resort but most prescribed because of its benefit.
Types of insulin are many and include:

Rapid-acting insulin
Long-acting insulin
Intermediate options

Insulin administration:
Injections. You can use a fine needle and syringe or an insulin pen to inject insulin under your
skin.
Insulin pens look similar to ink pens, and are available in disposable or refillable
varieties. Needles are available in a variety of sizes, so you can find one that's most comfortable
for you.
An insulin pump a device about the size of a cellphone worn on the outside of your body. A
tube connects a reservoir of insulin to a catheter that's inserted under the skin of your abdomen.
This type of pump can be worn in a variety of ways, such as on your waistband, in your pocket,
or with specially designed pump belts.

Role of Stem Cell in Diabetes treatment

1. Stem cells and their therapeutic potential:
Stem cell has exceptional ability to proliferate and differentiate into specialized cell types
under appropriate microenvironment. The stem cells have the potential to become any
type of specialized cell such as a myocyte, blood cell, hepatocyte and brain cell (Fig. 1).

Fig 1 Self renewal and differentiation potential of the stem cells

Fig 2 Different types of stem cell resources with a potential to be developed into insulin secreting
cells
2. Adult stem cells and diabetes
2.1 Pancreatic stem cells
The pancreas is an organ of first choice to be looking for the potential
stem cells. Animal studies have shown that the availability of small
amounts of pancreatic tissue would restore the maximum pancreatic b-cell
mass (Bonner-Weir et al., 1993).

Studies have shown that the islets of both rodent and human contains multi
potent stem cells (Eberhardt et al., 2006; Zulewski et al., 2001)
Research proves two facts, first the existence of pancreatic stem cell and
second the b-cells can be formed from non-b-cells.

2.2 Haemopoietic progenitor cells

For HSC transplant, we mobilize the patient's hematopoietic SC from bone
marrow to the blood with the use of low dose cyclophosphamide and
granulocyte colony-stimulating factor. Then the hematopoietic SC are
collected from peripheral blood by leukapheresis and cryopreserved. The
cells are re-injected intravenously. This is a lymphoablative scheme, as we
destroy most of the patient's lymphocyte clones, which include both
autoreactive and non-autoreactive, and we recover the immunologic
system with AHSCT. This phenomenon is called immunologic reset.
2.3 Other adult stem cells
Liver and small intestine can also act as a source of beta-cells.
Production of insulin secreting beta cells from the stem cells of the small
intestine (Suzuki et al., 2003; Yoshida et al., 2002), salivary glands
(Okumura et al., 2003) and adipose tissue (Timper et al., 2006).
3. ESCs and diabetes
A five-step protocol for differentiation of hES (human embryonic stem) cells to
Pancreatic hormone expressing cell. First focused on generating DE, followed by PDX1expressing
cells
and,
finally,
insulin-expressing
cells
(http://www.med.upenn.edu/timm/documents/Klaus_DAmour.pdf)

4. Induced pluripotent stem cells and diabetes

The production of pluripotent stem cells from non-pluripotent resource is referred
as induced pluripotency. Somatic cells can be reprogrammed to produce
pluripotent stem cell under specific conditions and such cell is known as induced
pluripotent stem cell (iPSC). Induced pluripotency is achieved by directed
expression of specific transcription factors (Yamanaka, 2008).
In vitro differentiation protocol that guaides the differentiation of induced
pluripotent stem (iPS) cells into insulin-producing cells.(A) Stepwise

differentiation of iPs cells onto insulin-producing cells.(B) combination of factors

used to guide the differentiation, (C) specific markes used to evaluate the
corresponding stage of differentiation.

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474639/ )
5. Safety concerns
Safety aspects: Safe administration and potential risk of teratoma
formation.
Transplantation issues: Transplantation complications and acclimatization
in the tissue microenvironment.
Scale up issues: Scale up potential of stem cells.
Ethical issues: Ethical issues concerned with the use of ESCs.
Side effects