The basic metabolic defect in type 2 DM is either a delayed insulin secretion relative to glucose load (impaired insulin secretion), or the peripheral tissues are unable to respond to insulin (insulin resistance).

1. TYPE 2
DIABETES
MELLITUS

2. TYPE 2 DIABETES MELLITUS
The basic metabolic defect in type 2
DM is either a delayed insulin
secretion relative to glucose load
(impaired insulin secretion), or the
peripheral tissues are unable to
respond to insulin (insulin
resistance).
Type 2 DM is a heterogeneous
disorder with a more complex
etiology and is far more common
than type 1, but much less is known
about its pathogenesis.A number of
factors have been implicated though,
but HLA association and autoimmune
phenomena are not implicated.

3. ABOUTTYPE 2- DM
Type 2 diabetes mellitus (DM) is a chronic metabolic
disorder in which prevalence has been increasing steadily
all over the world.
As a result of this trend, it is fast becoming an epidemic
in some countries of the world with the number of
people affected expected to double in the next decade
due to increase in ageing population, thereby adding to
the already existing burden for healthcare providers,
especially in poorly developed countries.

5. METABOLIC DEFECTS IN
DIABETES
• Decreased response of peripheral tissues,
especially skeletal muscle, adipose tissue,
and liver, to insulin (insulin resistance)
• Inadequate insulin secretion in the face of
insulin

6. PATHOPHYSIOLOGY
Genetic Factors
Genetic component has a stronger basis for type 2 DM
than type 1A DM.
• Although no definite and consistent genes have been
identified, multifactorial inheritance is the most important
factor in development of type 2 DM:
i)There is approximately 80% chance of developing
diabetes in the other identical twin if one twin has the
disease.
ii) A person with one parent having type 2 DM is at an
increased risk of getting diabetes, but if both parents have
type 2 DM the risk in the offspring rises to 40%.

7. Constitutional factors
• Certain environmental factors such
as obesity, hypertension, and level of
physical activity play contributory
role and modulate the phenotyping
of the disease.

8. INSULIN
RESISTANCE
• . i) Resistance to action of insulin
impairs glucose utilisation and
hence hyperglycaemia.
• ii) There is increased hepatic
synthesis of glucose.
• iii) Hyperglycaemia in obesity is
related to high levels of free
fatty acids and cytokines (e.g.
TNF-α and adiponectin) affect
peripheral tissue sensitivity to
respond to insulin.

9. INSULIN
RESISTANCE
EAT FOOD
MAKE
INSULIN
CELLS RESIST
INSULIN
SUGAR
STORES AS
FAT
FEEL TIRED
AND
HUNGRY

10. • The precise underlying molecular defect responsible for
insulin resistance in type 2 DM has yet not been fully
identified. Currently, it is proposed that insulin
resistance may be possibly due to one of the following
defects:
a) Polymorphism in various post-receptor
intracellular signal pathway molecules.
b) Elevated free fatty acids seen in obesity may
contribute e.g. by impaired glucose utilisation in the
skeletal muscle, by increased hepatic synthesis of
glucose, and by impaired β-cell function.
c) Insulin resistance syndrome is a complex of
clinical features occurring from insulin resistance and its
resultant metabolic derangements that includes
hyperglycaemia and compensatory
hyperinsulinaemia.

11. IMPAIRED INSULIN SECRETION
• i) Early in the course of disease, in response
to insulin resistance there is compensatory
increased secretion of insulin
(hyperinsulinaemia) in an attempt to
maintain normal blood glucose level.
• ii) Eventually, however, there is failure of β-
cell function to secrete adequate insulin,
although there is some secretion of insulin i.e.
cases of type 2 DM have mild to moderate
deficiency of insulin (which is much less
severe than that in type 1 DM) but not its
total absence.

12. a) Islet amyloid polypeptide (amylin) which forms fibrillar
protein deposits in pancreatic islets in longstanding cases of
type 2 DM may be responsible for impaired function of b-cells of
islet cells.
b) Metabolic environment of chronic hyperglycaemia
surrounding the islets (glucose toxicity) may paradoxically
impair islet cell function.
c) Elevated free fatty acid levels (lipotoxicity) in these cases may
worsen islet cell function.

13. INCREASED HEPATIC GLUCOSE
SYNTHESIS
One of the normal roles played by insulin is to
promote hepatic storage of glucose as glycogen and
suppress gluconeogenesis. In type 2 DM, as a part
of insulin resistance by peripheral tissues, the liver
also shows insulin resistance i.e. in spite of
hyperinsulinaemia in the early stage of disease,
gluconeogenesis in the liver is not suppressed.
This results in increased hepatic synthesis of
glucose which contributes to hyperglycaemia in
these cases.

15. PATHOPHYSIOLOGY
Impaired insulin secretion in
pancreas.
Increased glucose production
in liver
Increased glucose Leads to
receptoor and post receptor
defects .
Insulin resistance in peripheral
tissues (muscles)
Type 2 diabetes
mellitus

16. FACTORS CAUSINGTYPE 2 DIABETES
Genetic Factors
•Concordance in identical twins 80%
•Both parents diabetic 50% risk to the child.
Constitutional Factors
•Obesity
•Hypertension
•Low Physical Activity
Decreased Insulin Secretion
•Amylin
•GlucoseToxicity Of Islets
•Lipotoxicity.
Insulin resistannce
•Receptor and post receptor
defects
•Impaired glucose utilisation.
Increased hepatic glucose synthesis
Hyperglycaemia
TYPE 2 DM

17. CLINICAL FEATURES:
i)This form of
diabetes generally
manifests in middle
life or beyond, usually
above the age of 40.
ii)The onset of
symptoms in
type 2 DM is slow
and insidious.
iii) Generally, the
patient is
asymptomatic when
the diagnosis is made
on the basis of
glucosuria or
hyperglycaemia during
physical examination,
or may present with
polyuria and
polydipsia.
iv)The patients
are frequently
obese and have
unexplained
weakness and
loss of weight.

18. SYMPTOMS
Increased
thirst
Frequent
urination
Increased
hunger
Unintended
weight loss
Blurred vision
Slow-healing
sores
Frequent
infections
Numbness or
tingling in the
hands or feet

19. CAUSES
Exactly why this happens is unknown, but being
overweight and inactive are key contributing
factors
The pancreas is unable to produce enough
insulin to manage blood sugar levels.
Cells in muscle, fat and the liver become
resistant to insulin. Because these cells don't
interact in a normal way with insulin, they don't
take in enough sugar.

20. RISK
FACTORS
Overweight. Fat distribution. Inactivity.
Family history.
Race and
ethnicity. .
Blood lipid levels.
Age. Prediabetes.
Pregnancy-related
risks.
Polycystic ovary
syndrome.
Areas of darkened
skin, usually in the
armpits and neck.

21. COMPLICATIONS
Heart and
blood vessel
disease.
Nerve damage
(neuropathy)
in limbs.
Other nerve
damage.
Kidney
disease.
Eye damage.
Skin
conditions.
Slow healing.
Hearing
impairment. H
Sleep apnea.
Dementia.

22. TYPE 2 DIABETES
COMPLICATIONS
• Type 2 diabetes affects
many major organs,
including your heart,
blood vessels, nerves, eyes
and kidneys.Also, factors
that increase the risk of
diabetes are risk factors
for other serious chronic
diseases.

23. Heart and blood vessel
disease. Diabetes dramatically
increases your risk of various
cardiovascular problems, including
coronary artery disease with chest pain
(angina), heart attack, stroke, narrowing
of the arteries (atherosclerosis) and
high blood pressure.

24. Nerve damage (neuropathy). Excess
sugar can injure the walls of the tiny blood
vessels (capillaries) that nourish your nerves,
especially in the legs.This can cause tingling,
numbness, burning or pain that usually begins
at the tips of the toes or fingers and gradually
spreads upward. Poorly controlled blood
sugar could cause you to eventually lose all
sense of feeling in the affected limbs.Damage
to the nerves that affect the gastrointestinal
tract can cause problems with nausea,
vomiting, diarrhea or constipation. For men,
erectile dysfunction may be an issue.

25. Kidney damage (nephropathy).The kidneys
contain millions of tiny blood vessel clusters that
filter waste from your blood. Diabetes can
damage this delicate filtering system. Severe
damage can lead to kidney failure or irreversible
end-stage kidney disease, which requires dialysis
or a kidney transplant.
Eye damage. Diabetes can damage the blood
vessels of the retina (diabetic retinopathy),
potentially causing blindness. Diabetes also
increases the risk of other serious vision
conditions, such as cataracts and glaucoma.

26. Foot damage. Nerve damage in the feet or poor blood flow to the
feet increases the risk of various foot complications. Left untreated,
cuts and blisters can become serious infections that may ultimately
require toe, foot or leg amputation.
Skin and mouth conditions. Diabetes may leave you more
susceptible to infections of the skin and mouth, including bacterial and
fungal infections. Gum disease and dry mouth also are more likely.
Pregnancy complications. High blood sugar levels can
be dangerous for both the mother and the baby.The
risk of miscarriage, stillbirth and birth defects
increases when diabetes isn't well-controlled. For
the mother, diabetes increases the risk of diabetic
ketoacidosis, diabetic eye problems (retinopathy),
pregnancy-induced high blood pressure and
preeclampsia.

27. Slow healing. Left untreated,
cuts and blisters can become
serious infections, which may heal
poorly. Severe damage might
require toe, foot or leg
amputation.
Hearing impairment. Hearing
problems are more common in
people with diabetes.

28. Sleep apnea. Obstructive sleep apnea is
common in people living with type 2 diabetes.
Obesity may be the main contributing factor
to both conditions. It's not clear whether
treating sleep apnea improves blood sugar
control.
Dementia. Type 2 diabetes seems to
increase the risk of Alzheimer's disease
and other disorders that cause dementia.
Poor control of blood sugar levels is
linked to more-rapid decline in memory
and other thinking skills.

29. DIAGNOSIS
Random blood sugar
test
Fasting blood sugar
test.
Oral glucose
tolerance test.
Screening

30. DIAGNOSTIC TESTS INCLUDE:
GLYCATED HEMOGLOBIN (A1C)
TEST.
This blood test indicates your average blood sugar
level for the past two to three months.
It measures the percentage of blood sugar
attached to the oxygen-carrying protein in red
blood cells (hemoglobin).
The higher your blood sugar levels, the more
hemoglobin you'll have with sugar attached.
An A1C level of 6.5 percent or higher on two
separate tests indicates diabetes.

31. RANDOM BLOOD SUGARTEST.
A blood sample will be taken at a random time and
may be confirmed by repeat testing.
Blood sugar values are expressed in milligrams per
deciliter (mg/dL) or millimoles per liter (mmol/L).
Regardless of when you last ate, a random blood
sugar level of 200 mg/dL (11.1 mmol/L) or higher
suggests diabetes, especially when coupled with any
of the signs and symptoms of diabetes, such as
frequent urination and extreme thirst.

32. FASTING BLOOD SUGARTEST.
A blood sample will be taken after
an overnight fast.
A fasting blood sugar level less than
100 mg/dL (5.6 mmol/L) is normal.
A fasting blood sugar level from 100
to 125 mg/dL (5.6 to 6.9 mmol/L) is
considered prediabetes.
If it's 126 mg/dL (7 mmol/L) or
higher on two separate tests, you
have diabetes.

33. ORAL GLUCOSETOLERANCE
TEST
This test is less
commonly used than
the others, except
during pregnancy.
You'll need to fast
overnight and then
drink a sugary liquid
at the doctor's office.
Blood sugar levels
are tested
periodically for the
next two hours.
Results are
interpreted as
follows:
Less than 140 mg/dL
(7.8 mmol/L) is
normal.
140 to 199 mg/dL
(7.8 mmol/L and 11.0
mmol/L) is diagnosed
as prediabetes.
200 mg/dL (11.1
mmol/L) or higher
after two hours
suggests diabetes.

34. SCREENING.
The American Diabetes Association
recommends routine screening with diagnostic
tests for type 2 diabetes in all adults age 45 or
older and in the following groups:
People younger than 45 who are overweight or
obese and have one or more risk factors
associated with diabetes
Women who have had gestational diabetes
People who have been diagnosed with
prediabetes
Children who are overweight or obese and who
have a family history of type 2 diabetes or other
risk factors

35. TREATMENT
Healthy eating
Regular exercise
Weight loss
Possibly, diabetes medication
or insulin therapy
Blood sugar monitoring

36. REFERNCES
➢ Pathologic Basis of Disease
by Robbins & Cotran .
➢ Textbook of Pathology
(2015) by Harsh Mohan,7th
Edition.
➢ Goodman and Gilman's The
Pharmacological Basis of
Therapeutics, 13th Edition
➢ Edited By-
➢ Pharma campus
➢ Contributed by -
Ms.Vijaya Dhamane-
shri.d.d.vispute college of
pharmacy and research
center.