Disorder of Endocrine Pancreas

Diabetes Mellitus
Hammad
Nursing lecturer
KMU-INS
Objectives
• By the end of the class student will be able to,
• Review of Anatomy & Physiology of endocrine pancreas.
• Briefly discuss the classification of diabetes mellitus (DM)
• Discuss etiology, pathophysiology, and clinical manifestations
of Type 1 DM & Type 2 DM.
• Identify pathogenesis and manifestations of the acute and
chronic complications of diabetes mellitus.
 Pancreas
• The pancreas is a long, slender organ, most of which is located
posterior to the bottom half of the stomach. Although it is primarily
an exocrine gland, secreting a variety of digestive enzymes,
Functioning as an exocrine gland, the pancreas excretes enzymes
to break down the proteins, lipids, carbohydrates, and nucleic acids
in food. Functioning as an endocrine gland, the pancreas secretes
the hormones insulin and glucagon to control blood sugar levels
throughout the day.

• Its pancreatic islets —clusters of cells formerly known as the islets

of Langerhans—secrete the hormones glucagon from the center of
alpha cells, insulin from the periphery of beta cells, somatostatin,
and pancreatic polypeptide (PP).
 Physiology
• The alpha cell produces the hormone glucagon and makes up
approximately 20 percent of each islet. Glucagon plays an
important role in blood glucose regulation; low blood glucose
levels stimulate its release.

• The beta cell produces the hormone insulin and makes up

approximately 75 percent of each islet. Elevated blood glucose
levels stimulate the release of insulin.
 Conti…
• The delta cell accounts for four percent of the islet cells and
secretes the peptide hormone somatostatin. Recall that
somatostatin is also released by the hypothalamus (as
GHIH).

• The stomach and intestines also secrete it. An inhibiting

hormone, pancreatic somatostatin inhibits the release of both
glucagon and insulin.

• The PP cell accounts for about one percent of islet cells and
secretes the pancreatic polypeptide hormone.
 CONTI..
• It is thought to play a role in appetite, as well as in the
regulation of pancreatic exocrine and endocrine secretions.

• Pancreatic polypeptide released following a meal may reduce

further food consumption; however, it is also released in
response to fasting.
 Diabetes Mellitus
• Diabetes Mellitus (sugar diabetes) is a disease characterized
by high levels of sugar (glucose) in the blood.

• The disease was given its name because of the glucose

excretion in the urine.

(The term "diabetes" mellitus (honey sweet) was added by

Thomas Willis (Britain) in 1675 after rediscovering the sweetness
of urine and blood of patients).

• It is endocrine and metabolic disorder.

Diabetes Mellitus

The disease can be classified

into several types, depending
on its cause.
 Cause
• Diabetes mellitus is caused by an absolute or relative lack of
insulin that, among other consequences, leads to an increase in
plasma glucose concentration.
TYPE-I (Insulin-Dependent Diabetes
Mellitus)

(IDDM)
 IDDM or Type-I DM
• In type I (insulin-dependent diabetes mellitus [IDDM],
previously called juvenile diabetes; there is an absolute lack
of insulin, so that the patient needs an external supply of
insulin.

• The condition is caused by a lesion in the beta cells of the

pancreas, as a rule produced by an autoimmune mechanism
that may, in certain circumstances, have been triggered by a
viral infection.
 Pathophysiology of type 1 DM
• Type 1 diabetic mellitus is due to type IV hypersensitivity
response (cell mediated response) where persons own T
cells attack pancreas. Normally T cells react against
antigen which prevent to attack other body organs, is called
T cell self tolerance.
• In DM because of triggering factor lose of self tolerance of
T cells occur. And T cells specifically target beta cells of
pancreas. T cells coordinate other cells (autoantibodies)
and target beta antigen cells and destroy them, resulting in
less insulin and glucose pile up in blood and can not go
into the cell.
• After the death of the beta cells, the autoantibodies again
disappear.
 Pathophysiology of type 1 DM
• One gene in chromosome number 7, human leukocyte antigen
(HLA) is important for regulation of immune response. This
gene is encode for Major histocompatibility complex(MHA)
which is important for recognizing foreign molecule and
maintain self tolerance.
• MHC is serving palate, where antigen are present for immune
response.
• 90 % cells destroy until symptoms appear.
 Four major symptoms of type 1 DM
• Polyphagia
• Glycosuria
• Polyuria
• Polydipsia.
 Due to high blood glucose level in blood, adipose tissues and
muscles cells start breaking down fats (lipolysis) and proteins
(proteolysis) due to which weight lose occur and increase
feeling hungry called (polyphagia).
 Conti..
• Since glucose is osmotically active which leads to increase
circulation toward kidney this further leads to polyuria,
dehydration and polydipsia.
 Complications of type 1 DM
• Diabetic keto acidosis: During the process of lipolysis, liver
starts to make ketone bodies (acetic acid and beta
hydroxybeuteric acid) this condition is called diabetic
ketoacidosis. These ketone bodies are important because they
can be used by cell as a.
• Increase acidity of blood further cause three critical
symptoms.
1. Kussmule respiration
2. Hyperkalemia
3. High anion gape.
 Conti..
• Cells also contain transporter that exchange H ion.when the
blood gets acidic, means there is high level of hydrogen ions
resulting in H ions getting into the cell and potassium getting
out of the cell. This leads to hyperkalemia.
• Insulin also stimulates Na, K ATPase which help K in and Na
out of the cells, when there is no insulin K stays outside of
cells and cause hyperkalemia.
Type II (non-insulin-dependent
diabetes mellitus)
(NIDDM)
 Type-II DM or NIDDM
• Type II (non-insulin-dependent diabetes mellitus [NIDDM],
formerly called maturity onset diabetes; is by far the most
common form of diabetes. Here, too, genetic disposition is
important.
• However, there is a relative insulin deficiency: The patients
are not necessarily dependent on an exogenous supply of
insulin.
• Insulin release can be normal or even increased, but the target
organs have a diminished sensitivity to insulin.
 Type-II DM or NIDDM
• Most of the patients with type II diabetes are overweight. The
obesity is the result of a genetic disposition, too large an intake
of food, and too little physical activity.
• The imbalance between energy supply and expenditure
increases the concentration of fatty acids in the blood.
• This in turn reduces glucose utilization in muscle and fatty
tissues. The result is a resistance to insulin, forcing an increase
of insulin release.
 Pathophysiology of type 2 DM
• Obesity, HTN, and lack of exercise.
• For example excess fats in adipose tissues cause release of free
fatty acid adipokine which are signaling molecule for
inflammation.
• In type 2 diabetic mellitus the body produces more insulin
resulting in hyperplasia (grow in number) and hypertrophy
(grow in size) of beta cells occur. But this works for a while.
• Along with insulin the beta cells also secretes Amylin over
time which build in islet.
 Conti..
• Beta cells become axuasted, die and shrink by compensation
called hypotropy.Then after it leads to hyperglycemia and
cause symptoms of type 1 DM.
• In type 2 DM, DKA is very uncommon, because there is still
some circulating insulin for which beta cells try to compensate
for insulin to regulate Na K pump.
 Complications of type 2 DM
• Hyperosmolar Hyperglycemia: The condition in which
plasma osmolarity gets increase and it leads to dehydration.
• Glucose act as a solute so the glucose level in the blood is high
which cause water come into the blood and cells become
shrink which leads to increase urination and dehydration.
 Sign and symptoms
• In acute insulin deficiency the absence of its effect on glucose
metabolism results in hyperglycemia. The extracellular
accumulation of glucose leads to hyperosmolarity which father
leads polyuria,polyphasia, polydipsia, and glycosuria.

• The transport maximum of glucose is exceeded in the kidney

so that glucose is excreted in the urine . This results in an
osmotic diuresis with renal loss of water (polyuria), Na+, and
K+, dehydration, and thirst, dry mouth.
 Other Symptoms
• Muscular weakness.
• Hyperlipidemia.
• Kussmaul breathing.
• weight loss.
Differences between type-1 and type-2 Diabetes Mellitus

• Type 1 • Type 2
• Young age • Middle aged, elderly
• Normal BMI, not obese • Usually overweight/obese
• No immediate family • Family history usual
history • Symptoms may be present for
• Short duration of symptoms months/years
(weeks) • Do not present with diabetic
• Can present with diabetic coma
coma (diabetic ketoacidosis) • Insulin not necessarily
• Insulin required required
• Previous diabetes in
pregnancy

These differences are not absolute

Gestational diabetes
 A form of glucose intolerance that is diagnosed in some
women during pregnancy.
 During pregnancy, gestational diabetes requires treatment to
normalize maternal blood glucose levels to avoid
complications in the infant.
 It is common in third trimester. Hormone interferes with
insulin action on insulin receptors.
 Conti..
 After pregnancy, 5% to 10% of women with gestational
diabetes are found to have type 2 diabetes.
 Women who have had gestational diabetes have a 20% to 50%
chance of developing diabetes in the next 5-10 years
Values of Diagnosis of Diabetes Mellitus

1mmol=18mg
 Management of DM
• The major components of the treatment of diabetes are:

A • Diet and Exercise

• Oral hypoglycaemic
B therapy

C • Insulin Therapy
Treatment and control
• Medications
– (insulin vs. hypoglycemic agents)
• Increase physical activity
– at least walk for 30 min. most days
• Appropriate diet
– vegetables
– fruit
– low in fat and carbohydrates
• Lifestyle changes
 Acute complications of DM
• Diabetic ketoacidosis
• Hyperglycemia hyperosmolar state
• Hypoglycemia
• Diabetic coma
 Chronic complications
• Diabetic cardiomyopathy, damage to the heart, leading to
diastolic dysfunction and eventually heart failure.
• Diabetic nephropathy, damage to the kidney which can lead
to chronic renal failure, eventually requiring dialysis..
• Diabetic neuropathy, abnormal and decreased sensation,
usually in a 'glove and stocking' distribution starting with the
feet but potentially in other nerves, later often fingers and
hands. When combined with damaged blood vessels this can
lead to diabetic foot.
Conti….
• Diabetic retinopathy, growth of friable and poor-quality new
blood vessels in the retina as well as macular edema (swelling
of the macula), which can lead to severe vision loss or
blindness.
• Macrovascular disease leads to cardiovascular disease, to
which accelerated atherosclerosis is a contributor:
• Coronary artery disease, leading to angina or myocardial
infarction ("heart attack")
• Diabetic myonecrosis ('muscle wasting')
• Stroke (mainly the ischemic type)
 References
• American diabetic association.