Diabetes Mellitus

DIABETES
MELLITUS
By:
Thet-ul-Wafa Maqsood
Baqai Institute Of Pharmaceutical
Sciences,
Baqai Medical University,
Karachi, Pakistan.

OBJECTIVES:
• Introduction
• Types
• Pathogenesis
• Diagnosis
• Complications
• Treatment
• Counseling

INTRODUCTION:
Greek word Latin word
DIABETES MELLITUS
Siphon Sweet
Increased
output of
urine
Honey like
sweetness

Diabetes mellitus Is a
group of metabolic
diseases characterized
by increased levels of
glucose in the blood
(hyperglycemia)
resulting from defects
in insulin secretion,
insulin action, or both

Paul Langerhans
(Islets of langerhans of
pancreas)
Fredrick Bunting &
Charles Hebert
Nobel price 1923

Indian physician
Sushruta
Identify diabetes
Type 1 & Type 2
Indian physician
Term
“Madhumeha”
Honey urine

TARGET BLOOD GLUCOSE
LEVEL OF DIABETIC PATIENT
Types
Pre Prandial
Before meals
Post prandial
2 hours after meals
Non diabetic
4.0 to 5.9 mmol/L 7.8 mmol/L
Type 2 Diabetes 4 to 7 mmol/L 8.5 mmol/L
Type 1 Diabetes 4 to 7 mmol/L 9 mmol/L
Children with Type 1
Diabetes
4 to 8 mmol/L 10 mmol/L

NORMAL BLOOD SUGAR
RANGES
For the majority of healthy individuals, normal blood sugar
levels are as follows:
• Normal blood glucose level
• 4 mmol/L or 72 mg/ dl
• When operating normally
• 4.4 to 6.1 mmol/L (82 to 110 mg/dL)
• Shortly after a meal 7.8 mmol/L or 140 mg/dL

CONDITIONS OF DIABETES
There two conditions of diabetes are.
• Hyperglycemia
• Hypoglycemia

HYPERGLYCEMIA
When controlling your diabetes , but your blood glucose can
become too high .
This condition should be take seriously.

HYPOGLYCEMIA
Hypoglycemia occur when too little glucose is
present your blood.
• If not treated, low blood sugar lead to fainting
or seizure.
• A low blood sugar happen quickly & be life
threatening.
REASON :
• Improper diet
• Excessive amount of insulin injected.

EPIDEMEOLOGY
• The prevalence of diabetes is increasing rapidly
worldwide.
• The World Health Organization (2003) has predicted that by 2030
the number of adults with diabetes would have almost doubled
worldwide, from 177 million in 2000 to 370 million.
• The estimated worldwide prevalence of diabetes among
adults in 2010 was 285 million (6.4%) and this value is
predicted to rise to around 439 million (7.7%) by 2030
(Shaw et al., 2010).

INCIDENCE OF DIABETES
Estimated 245 million people globally
20% of adult population.
5% of all death each year.

80% of people with diabetes live in low & middle income
countries
The global incidence of DM is rising & the number of
effected is projected to exceed 300 million by year 2025

Hyperglycemia
Diabetes
Mellitus
Type I
Type II
Diabetes
Insipidus
Gestational
Diabetes

TYPES
• Type 1 diabetes
• In Type 1 diabetes, the pancreas
(a large gland behind the
stomach) fails to produce insulin.

TYPES I (CONT.)
Symptoms
Type I Diabeties

DM TYPES I (CONT.)
Cause
• The exact cause is not
known.
• Can be autoimmuned.
• Or may possibly triggered
by a virus. This destroys
the part of the pancreas
which produces insulin.

TYPE 2 DIABETES
• In Type 2 diabetes, the body cells are
unable to use insulin properly (insulin
resistance).

GESTATIONAL DIABETES
What is Gestational
diabetes?
• Gestational Diabetes is a form
of diabetes that occurs during
pregnancy and usually goes
away after the baby is born.

(CONT.)
Who is at risk of developing gestational diabetes?

(CONT.)
Commonly asked Questions about Gestational
diabetes:
• How will Gestational
Diabetes affect the
baby?
• Will the baby be born
with diabetes?
• What happens after the
baby is born?

DIABETES INSIPIDUS
• Diabetes insipidus (DI)
Is a condition characterized
by excessive thirst and
excretion of large amounts of
severely diluted urine,
• No concern with elevated
blood glucose levels.

DIABETES INSIPIDUS
(CONT).Types Of Diabetes Insipidus:
Central Diabetes Insipidus
(CDI)
•Due to deficiency of antidiuretic hormone (ADH).
Nephrogenic Diabetes
Insipidus (NDI),
•which is due to kidney or nephron dysfunction

DIABETES INSIPIDUS
(CONT).
Signs and symptoms

DIABETES INSIPIDUS
(CONT.).
• Presentation:
It may present with
• fever,
• vomiting,
• diarrhea.

DIABETES INSIPIDUS
(CONT).
•Causes:
• Serious Head injury.
• Pituitary Tumor.
• Deficiency of Anti diuretic hormone (ADH).
• kidney or nephron dysfunction

RISK FACTORS:
Related to Diabetes Mellitus (DM)

PATHOPHYSIOLOGY OF
DIABETES
As blood glucose rises, the
body sends a signal to
the pancreas, which
releases insulin.

NORMAL PHYSIOLOGY
• Insulin is released by beta cells (β
cells) in to the blood
• Beta cells (β cells) are found in
the islets cells of pancreas
• Beta cells response to high level
of blood glucose and secrete
insulin
• Insulin absorb the glucose from
the blood for:-
• use as fuel
• conversion to other needed
molecules
• storage

FUNCTIONS OF INSULIN:-
• Balance glucose level
• Inhibit breakdown of glycogen
• Inhibit the process of gluconeogenesis
• Stimulate transport of glucose in to fat and muscle cells
• Stimulate the storage of glucose in glycogen form
• Stimulate the protein synthesis

CARBOHYDRATE
METABOLISM
• Carbohydrates are metabolized in the body
to glucose.
• CNS uses glucose as its primary energy
source. This is independent of insulin.
• Glucose is taken by the muscle to produce
energy (insulin required).
• Glucose is stored in the liver as glycogen
and in adipose tissues as fat.
• Insulin is produced and stored by the β-
cells of the pancreas 49

PATHOPHYSIOLOGY OF DIABETES
When you eat, your body
breaks food down into glucose.
Glucose is a
type of sugar that is
your body’s
main source
of energy.
a
type of sugar that is
your body’s
main source
of energy.

PATHOPHYSIOLOGY OF
DIABETES MELLITUS TYPE 1
It is a slowly T cell mediated
autoimmune diseases
in which β cells are destroyed
Symptoms occur when 70-90% cells are
destroyed
Due to destruction of beta cells insulin is
unable to release or poorly released
Resulting hyperglycemia

HOW Β CELLS ARE
DESTROYED:-
 beta cells are destroyed due
to
 Beta cell antibodies
production like GAD enzyme
antibodies
 Insulitis in which infiltration of
islets with mononuclear cells

PATHOPHSIOLOGY OF
DIABETES MELLITUS TYPE 1
The high blood glucose level
causes kidneys to excrete
glucose in the urine
(glycosuria)
Due to which the osmotic
pressure of the urine increases
Resulting inhibition of water
reabsorption by the kidneys
The net effect will be increased
urine production (polyuria)
and fliud loss
Lost blood volume will be
replaced from water held in
body cells and other body
compartments causing
dehydration and increased
thirst (polydipsia)

TYPE 2 DIABETES MELLITUS
PATHOPHYSIOLOGY
• Insulin resistance
• Body tissues do not respond to insulin
• Results in hyperglycemia
• Decreased (but not absent) production
of insulin
• Due to which blood glucose level
increases

TYPE 2
PATHOPHYSIOLOGY
• Resistance of insulin is due to
• Reduction of insulin cells
• Life style :- overeating especially obesity
may lead to resistance of insulin

DIAGNOSIS AND
COMPLICATIONS
OF DIABETES

DIAGNOSIS AND TEST:
• Symptoms of type
1 diabetes often
appear suddenly
and are often the
reason for
checking blood
sugar levels. The
American Diabetes
Association (ADA)
has recommended
screening
guidelines. The
ADA recommends
that the following
people be
screened for
diabetes

ANYONE WITH A BODY
MASS INDEX HIGHER THAN
25, REGARDLESS OF AGE,
• who has additional
risk factors, such as
high blood pressure,
a sedentary lifestyle,
a history of
polycystic ovary
syndrome, having
delivered a baby
who weighed more
than 9 pounds, a
history of diabetes in
pregnancy, high
cholesterol levels, a
history of heart
disease, and having
a close relative with
diabetes.

ANYONE OLDER THAN
AGE 45
• is advised to receive
an initial blood
sugar screening,
and then, if the
results are normal,
to be screened
every three years
thereafter.

TESTS FOR TYPE 1 AND TYPE 2
DIABETES AND PREDIABETES
• 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
hemoglobin, the oxygen-carrying protein in red
blood cells. 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 that you have diabetes. An
A1C between 5.7 and 6.4 percent indicates
prediabetes. Below 5.7 is considered normal.
• If the A1C test results aren't consistent, the test isn't
available, or if you have certain conditions that can
make the A1C test inaccurate — so— your doctor
may use the following tests to diagnose diabetes:

• Random blood sugar
• : A blood sample will be
taken at a random time.
Regardless of when you
last ate, a random blood
sugar level of 200
milligrams per deciliter
(mg/dL) — 11.1 millimoles
per liter (mmol/L) — or
higher suggests diabetes.

• Fasting blood sugar test:
• 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.

• Oral glucose tolerance test:
• For this test, you fast overnight,
and the fasting blood sugar
level is measured. Then you
drink a sugary liquid, and blood
sugar levels are tested
periodically for the next two
hours. A blood sugar level less
than 140 mg/dL (7.8 mmol/L) is
normal. A reading of more than
200 mg/dL (11.1 mmol/L) after
two hours indicates diabetes. A
reading between 140 and 199
mg/dL (7.8 mmol/L and 11.0
mmol/L) indicates prediabetes.
If type 1 diabetes is suspected, your urine will be tested to look for the presence of
a byproduct produced when muscle and fat tissue are used for energy when the
body doesn't have enough insulin to use the available glucose (ketones).

COMPLICATIONS:
• Possible complications include:
• Cardiovascular disease.
• Diabetes dramatically increases
the risk of various cardiovascular
problems, including coronary
artery disease with chest pain
(angina), heart attack, stroke
and narrowing of arteries
(atherosclerosis). If you have
diabetes, you are more likely to
have heart disease or stroke.

COMPLICATIONS:
Nerve damage (neuropathy). Excess sugar
can injure the walls of the tiny blood vessels (capillaries)
that nourish your nerves, especially in your legs. This can
cause tingling, numbness, burning or pain that usually
begins at the tips of the toes or fingers and gradually
spreads upward. Left untreated, you could lose all sense
of feeling in the affected limbs. Damage to the nerves
related to digestion can cause problems with nausea,
vomiting, diarrhea or constipation. For men, it may lead
to erectile dysfunction.

COMPLICATIONS:
 Kidney damage (nephropathy). The kidneys contain
millions of tiny blood vessel clusters (glomeruli) 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 may require
dialysis or a kidney transplant.
 Eye damage (retinopathy). Diabetes can damage the
blood vessels of the retina (diabetic retinopathy), potentially
leading to blindness. Diabetes also increases the risk of
other serious vision conditions, such as cataracts and
glaucoma.

COMPLICATIONS:
 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 develop serious
infections, which often heal poorly. These infections may
ultimately require toe, foot or leg amputation.
 Skin conditions. Diabetes may leave you more susceptible
to skin problems, including bacterial and fungal infections.

How Does Insulin Work?
1.In a healthy person, insulin helps turn
food into energy -- in an efficient
manner.
2. The stomach breaks down
carbohydrates from food into sugars,
including glucose. Glucose then enters
the bloodstream, which stimulates the
pancreas to release insulin in just the
right amount.
3. Insulin, a hormone, allows glucose to
enter cells throughout the body, where
it is used as fuel. Excess glucose is
stored in the liver.

1.Successful treatment makes all the difference
to long-term health, and achieving balanced
diabetes treatment can be the key to living with
both type 1 and type 2 diabetes.
2.Treatment varies for each individual, not
simply on the type of diabetes that they have,
but also more individual-specific diabetic
treatment differences.

INSULIN
1.Inside the pancreas, beta cells make the hormone insulin. With each meal,
beta cells release insulin to help the body use or store the glucose it gets
from food.
2.Insulin is prescribed to people with type 1 diabetes. This is because type 1
diabetes destroys beta cells in the pancreas, meaning that the body can no
longer produce insulin.
2.People with type 2 diabetes make insulin, but their bodies don’t respond
well to it. Some people with type 2 diabetes may take pills or insulin shots to
help their bodies use glucose for energy.

Diabetes Medication
-Most diabetes drugs are designed for people
with type 2 diabetes who are unable to control
their blood sugar levels through strict diet and
exercise alone.
- But some, such as metformin, are sometimes
taken alongside insulin treatment for people
with type 1 diabetes.

Alpha-glucosidase inhibitors
-Alpha-glucosidase inhibitors are oral anti-
diabetic drugs used for diabetes mellitus type
2 that work by preventing the digestion of
carbohydrates (such as starch and table
sugar).
- Carbohydrates are normally converted into
simple sugars (monosaccharides), which can
be absorbed through the intestine.
- Hence, alpha-glucosidase inhibitors reduce
the impact of carbohydrates on blood sugar.

Mechanism of action
-Alpha-glucosidase inhibitors
are saccharides that act as competitive
inhibitors of enzymes needed to
digest carbohydrates, specifically alpha-
glucosidase enzymes in the brush border of
the small intestines.
-The membrane-bound intestinal alpha-
glucosidases hydrolyze oligosaccharides, trisa
ccharides, and disaccharides to glucose and
other monosaccharides in the small intestine.

Examples of alpha glucosidase inhibitors
- Acarbose (Precose):
Initial dose: 25 mg orally 3 times a day.
Maintenance dose: 50 to 100 mg orally 3
times a day.
- Miglitol (Glyset):
Initial dose: 25 mg orally 3 times a day at the
beginning (with the first bite) of each meal.
-Voglibose:
The recommended dose is 200-300 mcg 3
times/day.

Amylin analogs
- Amylin is a 37-amino acid peptide that is
stored in pancreatic beta cells and is co-
secreted with insulin.
-Amylin and insulin levels rise and fall in a
synchronous manner . Amylin and insulin have
complementary actions in regulating nutrient
levels in the circulation.
- Amylin is deficient in type 1 diabetes and
relatively deficient in insulin-requiring type 2
diabetes

-Amylin affects glucose control through several
mechanisms, including slowed gastric emptying,
regulation of postprandial glucagon, and reduction of
food intake.
- Glucagon-like peptide 1 (GLP-1) exhibits similar
properties as amylin, with the exception of insulin
secretory effects. Amylin, unlike GLP-1, does not
have insulin secretory effects, but both regulate
hyperglycemia in part through amelioration of
inappropriate glucagon secretion and gastric emptying

There is only one known example of amylin analog that is
pramlintide acetate that is an injectable effective in both type
1 and type 2 diabetes.

Biguanidine drugs
Mechanistic aspects:
-Biguanides do not affect the output of insulin, unlike
other hypoglycemic agents such as sulfonylureas and meglitinides.
-Therefore, not only are they effective in Type 2 diabetics but
they can also be effective in Type 1 patients in concert with
insulin therapy.
- The mechanism of action of biguanides is not fully understood.
Mainly used in Type II Diabetes, Metformin is considered to
increase insulin sensitivity in vivo, resulting in reduced plasma
glucose concentrations, increased glucose uptake, and decreased
gluconeogenesis.

Examples Of biguanides:
Metformin:
-widely used in treatment of diabetes mellitus
type 2
- 500 mg orally twice a day (with the morning
and evening meal)
Phenformin:
- withdrawn from the market in most
countries due to toxic effects.
Buformin:
- withdrawn from the market due to toxic
effects

SULFONYLUREAS
- Sulfonylurea (UK: sulphonylurea)
derivatives are a class of antidiabetic drugs.
-They are used in the management
of diabetes mellitus type 2. They act by
increasing insulin release from the beta
cells in the pancreas.
- There are two generations of sulfonylureas,
both being oral hypoglycemic agents used in
type diabetes mellitus.

Mechanism of action:
-Sulfonylureas bind to an ATP-dependent K+(KATP) channel
on the cell membrane of pancreatic beta cells.
-This inhibits a tonic, hyperpolarizing efflux of potassium,
thus causing the electric potential over the membrane to
become more positive.
-This depolarizationopens voltage-gated Ca2+ channels.
The rise in intracellular calcium leads to increased fusion
of insulin granulae with the cell membrane, and therefore
increased secretion of (pro)insulin.

Drugs in this class
First generation:
- Carbutamide
- Acetohexamide
-Chlorpropamide
- Tolbutamide
Second generation:
- Gliclazide
- Glibenclamide (glyburide)
- Glibornuride
- Glimepiride

THIAZOLIDINEDIONE
- Thiazolidinediones , also known
as glitazones, are a class of medications used
in the treatment of diabetes mellitus type 2
Mechanism of action:
- Thiazolidinediones or TZDs act by
activating PPARs (peroxisome proliferator-
activated receptors), a group of nuclear
receptors, with greatest specificity
for PPARγ (gamma). The
endogenous ligands for these receptors are
free fatty acids (FFAs) and eicosanoids

- When activated, the receptor binds
to DNA in complex with the retinoid X
receptor (RXR), another nuclear receptor,
increasing transcription of a number of
specific genes and decreasing transcription of
others.
- Although there are still many unknowns
about the mechanism of action of TZDs in
type 2 diabetes, it is clear that these agents
have the potential to benefit the full 'insulin
resistance syndrome' associated with the
disease. Therefore, TZDs may also have
potential benefits on the secondary
complications of type 2 diabetes, such as
cardiovascular disease.

Members of the class
Rosiglitazone (Avandia)
Pioglitazone (Actos)
Troglitazone (Rezulin)
Initial dose: 4 mg/day orally as a single daily
dose or in two divided doses. Doses may be
taken without regard to meals.
Maintenance dose: The dose may be
increased to 8 mg daily in patients who fail to
respond adequately following 12 weeks of
initial therapy.
Initial dose: 15 mg to 30 mg orally once a day.
Doses may be taken without regard to meals.
Maintenance dose: In patients who respond
inadequately to the initial dose, it may be
increased in increments up to 45 mg once
daily.

COUNSELING
Of a diabetic patient

WHY TO COUNSEL?
Diabetes
Mellitus
Chronic
Disease
Complications
Counseling
Improve
quality of life

THE SIX MOST
ASKED
QUESTIONS
ABOUT DIABETES

Q. WHAT IS
DIABETES?
Diabetes is a disease.

Q. CAN YOU
‘CATCH’ DIABETES?
No,

Q. AT WHAT AGE DO
YOU GET DIABETES?
A. Anyone can get diabetes at any age.

Q. WHAT TYPES OF
PEOPLE GET
DIABETES?
A. Anyone may develop diabetes.

Q. HOW CAN I TELL
IF I HAVE DIABETES?
A. By the symptoms.

Q. CAN DIABETES
BE CURED?
A. As yet there is no cure. However, excellent treatment is
available.

COUNSELING REGARDING
LIFESTYLE MODIFICATION
(NON-PHARMACOLOGICAL
THERAPY)
Exerc
ise
Smokin
g
Diet

DIABETES AND DIET
CHOOSE HIGH-FIBER, SLOW-
RELEASE CARBOHYDRATES
Instead of… Try these high-fiber options…
White rice Brown rice or wild rice
White potatoes (including fries and mashed
potatoes)
Sweet potatoes, yams, winter squash,
cauliflower mash
Regular pasta Whole-wheat pasta
White bread Whole-wheat or whole-grain bread
Corn Peas or leafy greens

DIABETES AND DIET
(CONT).
Be smart about sweets

DIABETES AND DIET
(CONT.).
Proceed with caution when it comes
to alcohol

DIABETES AND DIET (CONT.).
CHOOSE FATS WISELY
• Ways to reduce unhealthy fats and add healthy fats:
Instead of… Try these options…
vegetable oil or butter Cook with olive oil
chips or crackers, try snacking on nuts or seeds.
frying grill, broil, bake, or stir-fry.
Red meat. Serve fish 2 or 3 times week
cheese Add avocado to your
sandwiches
shortening or butter When baking, use canola oil

NUTRITIVE CHART
•Fruits:-
• 1 serving contain:-
protein 1 gm
carbohydrate 15 gm
Sodium 5 mg
Potassium 150 mg
Kcal 60

FRUIT ITEMS
Serving size:-
Grape fruit ½ medium
Grapes 22
Mango ½ medium
peach 1 small
pineapple ½ medium
Apple 1 medium

VEGETABLES
• 1 Serving contains:-
Protein 2 gm
Carbohydrate 5 gm
Sodium 10 mg
Potassium 200 mg
Kcal 25

VEGETABLES
Food items Serving size.
Cabbage ½ Cup
Carrot ½ Cup
Cauliflower ½ Cup
Cucumber 1 Cup
Onions ½ Cup
Peas 1/4 Cup
Potatoes ½ Cup

MEAT
1 serving contain:-
protein 8 gm
Fat 3 gm
Sodium 25 mg
potassium 100 mg
Kcal 55-75

MEAT
Food items Serving Size
Beef 1 Oz
Chicken 1 Oz
Fish 1 Oz
Large Egg 1

FOODS TO AVOID
• BANANA
• DATES
• WATER MELON
• ORANGE
• POMGRANATE
• PAPAYA
• Red meat

THERAPY)
• Diabetes and Exercise:
Type II
(desired level is 3-4 times a week)
Type I
(Care must be taken to have adequate metabolic control)
Exercise is not recommended if patient has poorly controlled
blood glucose level

THERAPY)
 Diabetes and Smoking

Diabetes Mellitus

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