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Blood Glucose• Normal Fasting Blood Glucose = 80 – 100 mg/dl
• Post-Prandial Blood Glucose = 100 – 120 mg/dl
mmol/lmg/dl
1.730
4.480
8.3150
14.0250
22.2400
1.Carbohydrate of diet
2.Liver glycogen by glycogenolysis
3.10% of Fat of diet by gluconeogenesis
4.58% of Protein of diet by gluconeogenesis
5.Lactate from blood & RBCs by gluconeogenesis
Sources of Blood Glucose
Factors Regulating Blood Glucose
1.Gastrointestinal tract factors
2.Hepatic factors (Glucostat organ)
3.Renal factors
4.Hormonal factors
1.Gastrointestinal factors:
• Oral carbohydrate diet stimulates more insulin
than intra-venous glucose
• This may be due to secretion of glucagon-like
substance by intestine which stimulates -cells
of pancreas to secrete more insulin
Factors Regulating Blood Glucose
Factors Regulating Blood Glucose
2.Hepatic factors (Glucostat organ):
A- If blood glucose level increased, liver decreases it by:
1. Oxidation of glucose (Glycolysis & Kreb’s)
2. Glycogenesis
3. Lipogenesis
B- If blood glucose level decreased, liver increases it by:
1. Glycogenolysis
2. Gluconeogenesis
3. Conversion to fructose and galactose into glucose
Factors Regulating Blood Glucose
3. Renal factors:
• Normal Renal Threshold for Glucose =
180 mg/dl
• Some patients may have Renal Diabetes,
in which Renal Threshold is less than
140 mg/dl
1. Glucagon:
29 amino acid polypeptide
Major target organ: liver
Have no receptors on muscle cell
Principal hormone for producing a rapid
increase in plasma glucose concentration
Dominates in Fasting State Metabolism
Stimulates production of glucose by
glycogenolysis and gluconeogenesis
Secretion is suppressed in hyperglycemia
4.Hormonal factors:
Endocrine response to hypoglycemia Glucagon Action on Cells
2. Epinephrine “fight or flight”
A catecholamine secreted by the adrenal medulla
Stimulates glucagon secretion and inhibits insulin
secretion
Stimulates glycogen breakdown (glycogenolysis)
and decreases glucose oxidation
Physical/emotional stress epinephrine
production, releasing glucose for energy
Gluconeogenesis
Lipolysis
Glycogenolysis
Only hormone (besides insulin) needed to keep you alive
Maintains general functioning of body
metabolism and regulates blood pressure
Secreted by adrenal cortex in response to ACTH of
pituitary gland
Cortisol causes breakdown of muscle protein,
leading to amino acid release in blood
Liver uses amino acids to make glucose
(Gluconeogenesis!)
Cortisol increases blood sugar!
3. Cortisol “Stress Hormone”
4. Growth Hormone (GH) Primary function: stimulates growth of soft
tissue, bone, and cartilage
Secondary function: Effect on plasma glucose:
1. Inhibition of glucose uptake by peripheral
cells
2. Stimulation of liver glycogenolysis
3. Acceleration of fatty acid catabolism
(Stimulation of gluconeogenesis)
Prolonged excess of GH (Acromegaly):
Mild hyperglycemia, abnormal Oral Glucose
Tolerance Test (OGTT)
5. ACTH
ACTH stimulates the production
of glucocorticoids
Glucocorticoids stimulate
gluconeogenesis
6. Thyroxin
• It increases the blood glucose level by:
1. Increases the rate of absorption of glucose
from intestine
2. Stimulates gluconeogenesis
3. Stimulates glycogenolysis
4. Thyroxine also stimulates glucose
oxidation in tissues
5. However the net effect of this hormone is
the increase in blood glucose level
7. Glucocorticoids • These hormones are secreted from zona fasiculata
• They are hyperglycemic (Insulin antagonistic action)
• They produce their effect by:
1. Inhibiting glucokinase
2. Stimulating glucose-6-phosphatase
3. Inhibiting tissue uptake of glucose
4. Stimulating gluconeogenesis
On the other hand, Glucocorticoids
5. Stimulating glycogenesis by increasing the
activity of glycogen synthase enzyme
8. Insulin First hormone identified (1920’s) by
Banting and Best
Tied string around pancreatic ducts of
dogs or removed ducts. Only thing left
were thousands of pancreatic islets,
Isolated protein…and discovered
insulin!
Insulin is a hormone that is needed to
convert sugars, starches, and other
food into energy needed for daily life
7. Insulin
Fed-state metabolism
• Circulating insulin
rapidly binds to
receptors on cell
surfaces, increases
glucose entry into
cells and alters
metabolic pathways
Action of
glucagon and
insulin on the
liver, muscle, and
adipose tissue.
Phases of Glucose Homeostasis
Nutritional
StatusWell-Fed Post-absorptive
Gluconeogenic
(early)Prolonged
Origin of
Blood
Glucose
ExogenousHepatic glycogen,
Gluconeogenesis
Hepatic
glycogen,
Gluconeogenesis
Gluconeo-
genesis
Tissues
Using
Glucose
All
All except liver.
Muscle, adipose
diminished rates
Brain & RBC's;
Small amount by
Muscle
Brain
Slow rate;
RBCs normal
Major Fuel
of the
Brain
Glucose Glucose Glucose Ketone bodies
glucose from
gluconeogenesis
(mostly lactate)
4 8 12 16 2 7 42
Exogenous
(glucose
from diet)
40
30
20
10
0
Glu
cose
Use
d g
/hr
Fed Post absorptive Gluconeogenic Prolonged
HOURS DAYS
Sources of blood glucose in the various nutritional states
glucose from
liver glycogen
glucose from
gluconeogenesis
(lactate + amino acids)
Maintenance of blood glucose concentration
depends on insulin and glucagon
Brain depends on glucose
Prolonged starvation has <25% decline in
glucose
Hyperglycemia – too little insulin
Hypoglycemia – too little intake or too much insulin
Summary of Blood Glucose Homeostasis
Under conditions where insulin levels are high, the
number of receptors declines and the target tissues
become less sensitive, resulting in “down regulation”
22%
45%
Glucose Homeostasis
Blood Glucose, What’s “normal”?
Pancreas Pancreas, controls blood glucose levels by
secreting hormones into the blood
Islet of Langerhans (, , )
1. -cells (20-30% of islet cells) Glucagon
2. -cells (60-70% of islet cells) Insulin
3. -cells (2-8% of islet cells) Somatostatin
After high
carbohydrate dietBetween
meals
Role of
Pancreas in
Normalizing
Blood
Glucose
Level
Distribution of Glucose After Meal
Insulin released when glucose is elevated in plasma
Insulin increases peripheral tissue uptake, so
muscle and fat cells remove glucose from blood
Cells breakdown glucose, releasing its energy in the
form of ATP (via glycolysis and Kreb’s cycle)
Liver and muscle store glucose as glycogen (short-
term energy reserve)
Adipose tissue stores glucose as fat (long-term
energy reserve)
Cells use glucose in protein synthesis
Insulin is the ONLY hormone that lowers circulating
glucose level!
Distribution of Glucose After Meal
Insulin Synthesis
Transcription and Translation of the
Insulin Protein First, the DNA coded information (blue helix) in the cell
nucleus is copied, or transcribed, to an RNA mirror
image (red strand).
Second, the ribosome (tan) translates the linear pattern
described in the RNA to construct a protein strand. This
translation is based on the Genetic Code (background
text).
Transfer-RNA's (Cross-like shapes) ferry (moving)
amino acids to the growing protein chain based on the
3-codon RNA sequence.
Finally, the Insulin protein strand folds itself into its
active form.
Transcription &
Translation of the
Insulin Protein
DNA coded information
inside the Nucleus
mRNA
tRNA
Ribosome
Insulin
molecule
Transcribed RNA
Tertiary
Structure
of Insulin
1
(24)
4
(21)
2
(30)
3
(35)
Preproinsulin
31 Arg
32 Arg
64 Lys
65 Arg
[Connecting peptide]
Aids in transporting insulin
through the membrane
Preproinsulin
Synthesized in Ribosomes
Aids in transporting insulin
through the membrane
Proinsulin
In Endoplasmic Reticulum
Insulin
In Golgi Apparatus
Synthesized in Ribosomes
In Endoplasmic Reticulum
In Golgi Apparatus
Leader
(Signal) chain
A chain 21 amino acids
B chain 30 amino acids
Post-translational
Processing of
Insulin
Mechanism of Action of Insulin
Muscle
Mechanism of Action of Insulin1. Increases peripheral tissue uptake (Fat, RBC’s
& Muscle cells)
NORMALLY IN THE BODY
Mechanism of Action of Insulin
1. Increases peripheral tissue uptake (Fat,
RBC’s & Muscle cells)
2. Induces synthesis of enzymes of:
a- Glycolysis (3 enzymes)
b- Kreb’s cycle (Pyruvate DH)
c- Pentose shunt (2 enzymes)
3. Stimulates glycogenesis (1 enzyme)
4. Inhibits glycogenolysis (1 enzyme)
Mechanism of Action of Insulin
5. Inhibits gluconeogenesis (4 enzymes)
6. Stimulates Lipogenesis (Supplies Acetyl
Co A, -Glycerol phosphate, NADPH &
ATP)
7. Inhibits lipolysis (1 enzyme)
8. Stimulate transamination (Pyruvate to
Alanine), (1 enzyme)
Glycolysis
Protein
synthesis
Lipogenesis
Glycogenesis1
2
3 4
Oral Glucose Tolerance Test (OGTT)
Collect fasting blood samples for determination
of blood glucose and urine samples for detection
of glucose in urine
Give the patient (1g/Kg body weight, max. 50 g)
glucose in half cup of water
Every 30 min. collect a blood samples and urine
samples, for 2.5 – 4 hr
Draw a relation between blood glucose level
(mg/dl) against time (hr)
Oral Glucose Tolerance Test (OGTT)
Renal
Diabetes
Severe
Diabetes
Moderate
Diabetes
Mild
DiabetesNormal ParameterNo
70 – 110
mg/dl
> 180 mg/dl140 – 180
mg/dl
70 – 140
mg/dl
70 – 110
mg/dl
Fasting
Blood
Glucose1
After 1 hrAfter 1 hrAfter 1 hrAfter 1 hrAfter 1 hrPeak
Time2
< 140 mg/dl> 270 mg/dl 230 – 270
mg/dl
< 180
mg/dl
< 140
mg/dl
Peak
Value3
2:00 hr4:00 – 5:00
hr
2:30 – 4:00
hr2:30 hr2:00 hr
Time of
return to
Fasting
Level
4
Present in the
Middle of the
Samples
Present in
all
Samples
Present in the
Middle of the
SamplesAbsentAbsent
Glucose
in
Urine
Samples
5
Oral Glucose Tolerance Test (OGTT)
A medical disorder
characterized by hyperglycemia
(elevated blood glucose level)
especially after eating
Diabetes Mellitus
“Diabetes“ is a Greek word meaning “passes
through, a siphon”, due to polyuria
“Mellitus” is a Greek word meaning “sweet”
This is due to the diabetic’s urine attracts flies &
bees because of its glucose content
The Ancient Chinese test for diabetes by observing
whether ants were attracted to a person’s urine
Diabetes
Disease in which the body:
Does not produce insulin, or
Does not properly use insulin
Diabetes Warning signs:
Extreme thirst (Polydipsia)
Frequent urination (Polyuria)
Unusual fatigue or drowsiness
Unexplained weight loss
Blurry vision from time to time
Diabetes is the leading cause of kidney
failure, blindness, and amputation in
adults, and can also lead to heart disease
Main Types of
Diabetes Mellitus (D.M.)
Type I (IDDM)
Insulin Dependent
Diabetes Mellitus
Type II (NIDDM)
Non-Insulin
Dependent Diabetes
Mellitus
Other Types of Diabetes Mellitus (D.M.)
(Non Type 1 – Non type 2)
•Type 3:
• Type 3A: Genetic defect in β-cell function
• Type 3B: Genetic defect in insulin action
• Type 3C: Diseases of the exocrine pancreas
• Type 3D: Caused by hormonal defects
(Endocrinopathies)
• Type 3E: Caused by chemicals or drugs
• Type 4: Gestational D.M.
It appears in 2 – 5% of all pregnancies
It is temporary & fully treatable under medical
supervision
About 20 – 50% go on to develop type II diabetes
Other Types of Diabetes Mellitus (D.M.)
Other Classes of D. M.
5. Diabetes insipidus:
due to deficiency of
Vasopressin (ADH)
polyuria
Other Classes of D. M.
6. Renal diabetes: due to congenital defect in
renal threshold for glucose (140 mg/dl or
less)
7. Stress diabetes (Emotional diabetes): due to
secretion of catecholamines
8. Bronze diabetes: due to excessive absorption &
deposition of iron in pancreas:
a) Hyperglycemia D.M.
b) Skin Bronze in color,
c) Liver Cirrhosis
9. Steroid diabetes: due to secretion or prolonged
administration of glucocorticoids
10. Pituitary diabetes: due to over-secretion of Growth
hormone (Acromegaly)
7. Experimental diabetes:
a) Alloxan diabetes Uncontrolled diabetes
b) Streptozotocin diabetes Controlled
diabetes
c) Surgical diabetes:
i. Total pancreatectomy
ii. Partial pancreatectomy
8. Drug-induced diabetes: large doses of
dehydroascorbic acid
Causes of Diabetes Mellitus
Insufficient production of Insulin
Increased production of anti-insulin hormones,
e.g.:
1. Cushing's syndrome ( Cortisone)
2. Hyperthyroidism ( Thyroid Hormone)
3. Acromegaly ( Growth Hormone)
21
Risk Factors for Diabetes Mellitus
3 1
4 2
5 6
7 8
9 10
Cellular phones and remote controls deprive us from walking!
20 times daily x 20 m = 400 m
Walking distance lost/year400x365 = 146,000 m
146 km = 25 h of walking
1 h of walking = 113-226 kcal
Energy saved =2800-6000 kcal
Rössner, 2002
High-Tech increases Body
Weight
0.4-0.8 kg adipose tissue
Increased Time at Computer/TV/Video
Decreases Time for Leisure-Time
Physical Activity
>
New Remote Control
Can Be Operated by
Remote
• Television watching became
even more convenient with
Sony’s introduction of a new
remote-controlled remote
control
• No more leaning
forward to get
remote from coffee
table means greater
convenience for TV
viewers
Eat to
Live!Live to Eat!
“EAT TO LIVE”
Intake = Expenditure
Weight Stable
“LIVE TO EAT”
Intake > Expenditure
Obese
reveals itself in childhood.
can be made worse from excessive lifestyle.
It is caused by the destruction of insulin-producing
cells (-cells of islets of Langerhans of pancreas)
IDDM may be due to:
1. -cell destruction may be due to:
a) -cell lesions (trauma or tumor)
b) Viral infection
c) Chemical toxins (rat poison)
2. Autoimmune mediated disorder
3. Idiopathic (Unknown cause)
Type I (IDDM)
Insulin Dependent Diabetes
It is an autoimmune disorder, so confused with
type II
Known by misleading names: Juvenile
(Childhood) onset diabetes (under 20–30 years)
Usually accompanied with loss of body weight
Characterized by Diabetic Ketoacidosis (DKA)
Diabetic Coma
Type I (IDDM)
Type I IDDM Lipid metabolism
Fatty acid production
Ketone formation
Decreased glucose
uptake & Protein
metabolism
Glycogenolysis
Gluconeogenesis
Decreased glucose
uptake
Symptoms of Type 1 Diabetes
Increased thirst
Increased hunger (especially after eating)
Dry mouth
Frequent urination (polyuria)
Unexplained weight loss (even though
you are eating and feel hungry)
Fatigue (weak, tired feeling)
Blurred vision
Labored respiration (heavy breathing, تنفس
(Kussmaul respirations) (جهذي
Loss of consciousness (rare)
In this case, the pancreas continues to
manufacture insulin. However, this production may
be inadequate or normal
For some unknown reason, the body develops
resistance to insulin, thus resulting in a relative
insulin deficiency
Type II (NIDDM)
Non-Insulin Dependent Diabetes
NIDDM may range from:
1. Insulin resistance with relative insulin deficiency, to:
2. Insulin secretary defect with insulin resistance
Insulin resistance may be due to:
a) Decreased number of insulin receptors, or
b) Insensitivity of insulin receptors to insulin
Type II (NIDDM)
DIABETES TYPE 2:
INSULIN RESISTANCE
This is a more complex problem than type I,
but is sometimes easier to treat
Known by misleading names: “Adult onset
diabetes” (over 40 years), “Obesity-related
diabetes” due to gain of body weight, or
“Insulin-resistant diabetes”
Chronic obesity leads to increased insulin
resistance that can develop diabetes
Type II (NIDDM)
Type II Diabetes Mellitus
Insulin resistance
Decreased glucose
uptake with any
amount of insulin
Insulin Receptors
Insulin Resistant Cell
Insulin Shock
People who accidentally take too much insulin
may be victims of insulin shock
The symptoms of insulin shock include:
Agitation
Trembling
Sweating
Pallor
Speech difficulty
Unconsciousness
الهياج
اإلرتعاد
التعرق
الشحوب
صعوبة الكالم
فقذ الوعي
Insulin Shock
Someone suffering from the preliminary
symptoms is given sugar in the form of sweets or
fruit
An unconscious patient is given an injection of
adrenaline into muscle, or glucose solution into a
vein
Symptoms of Type 2 Diabetes
Slow-healing sores or cuts
Itching of the skin (usually in the
vaginal or groin area)
Yeast infections
Recent weight gain
Numbness (نمل ؛ اخذرار) or tingling
of the hands and feet (نخز)
Impotence or erectile dysfunction
Bases of Treatment of
Diabetes Mellitus
It is treated with:
1. Insulin injections, human insulin is often
preferred in initiating insulin treatment because
it is less antigenic than animal-derived varieties
2. lifestyle adjustment
3. Monitoring of blood glucose levels
4. Experimental replacement of -cells (-cells
Transplant) may become clinically available in
future
5. Patient may requires immuno-suppressor drug,
e.g.: “Cyclosporine”
Type I (IDDM) Diabetes Mellitus
Type II may go unnoticed for years in patients
before diagnosis, due to milder symptoms (No
ketoacidosis) and can be sporadic
1. Patient must reduces body weight (Diet) or
Lifestyle Modification, which can restore insulin
sensitivity
2. Patient requires muscular exercise
3. Patient may require an oral antidiabetic drugs
4. When these failed, insulin therapy may be
necessary
Basis of Treatment of Type II (NIDDM)
Type I diabetes is usually prompted by
recent symptoms of:
Excessive urination (Polyuria)
Excessive thirst (Polydipsia)
Weight loss
Diabetic ketoacidosis (DKA)
The diagnosis of other types of
diabetes is made by:
Health screening
Detection of hyperglycemia
Signs & symptoms of D.M.
Diagnosis of Diabetes Mellitus
1. Two fasting plasma glucose level
above 125 mg/dl
2. Plasma glucose above 200 mg/dl two
hours after a 50 g glucose load
3. Symptoms of D.M. and a random
glucose above 200 mg/dl
4. Elevated glycosylated or glycated
hemoglobin (glucose bound to Hb,
HbA1C) of 6.0 or higher
Criteria for Diagnosis of Diabetes Mellitus
Hypoglycemia may occur because of:
An error in insulin dosage
A small or missed meal
Unplanned exercise
Hypoglycemia, usually respond rapidly
to the ingestion of sugar
All diabetics should carry candy,
lumps of sugar, or glucose tablets
Hypoglycemia
An identification card, indicating that the patient is
an insulin-treated diabetic, aids in recognizing
hypoglycemia in emergencies
Close family members should be instructed to
administer glucagon with an easy-to-use injection
device
Emergency medical personnel, after confirming
the hypoglycemia with a glucostick, should initiate
therapy with a rapid bolus injection of 25 ml of
50% glucose solution followed by a continuous IV
infusion of glucose
Manifestation & Complication of Diabetes
Hyperglycemia
Glucosuria
Hyperphagia (eating too much)
1- Carbohydrate Disturbances
Hyperlipemia
Fatty liver
Ketonemia
Ketoacidosis
Ketonuria
Coma
Manifestation & Complication of Diabetes
2- Lipid Disturbances
Hypercholesterolemia
Atherosclerosis
Gangrene
Amputation
Manifestation & Complication of Diabetes
2- Lipid Disturbances (Cont.)
Negative N2 balance
Weakness & wasting of muscles
3- Protein Disturbances
Manifestation & Complication of Diabetes
Osmotic diuresis
Polyuria
Dehydration
Polydepsia (Thirsty)
Manifestation & Complication of Diabetes
4- Water Disturbances
Cataract
Neuropathy
Nephropathy
Retinopathy
Blindness
5- Pathological Changes
Manifestation & Complication of Diabetes
Diabetic
Complication
Diabetic
Complication
Diabetic
Complication
• Diabetic Patients must examine feet
thoroughly, looking for blisters (بثور),
cuts (تخفيضات) and bruises (كدمات)
Diabetic Patients
Don't miss a spot
If you're unable to
see some parts of
your feet, use a
mirror.
Diabetes can damage nerves
(neuropathy), reducing the ability
to feel pain in your feet. That
means you may not notice a
small cut or blister until it
becomes a large sore.
Look for infection
• Athlete's foot is a common fungal infection
Serious Complications
Serious Complications of
Chronic hyperglycemia
Chronic hyperglycemiaGangrene of toes
Chronic hyperglycemia
Normal Diabetic retinopathy
Ophthalmoscope
Co
nti
nu
ou
s G
luco
se M
on
ito
r &
Insu
lin
Pu
mp
Insulin
pump
GLUCOSE MONITORING DEVICES
A device is now available for continuous
glucose measurement and continuous insulin
administration (i.e., a true artificial pancreas).
The MiniMed Continuous Glucose Monitoring
System (CGMS) measures glucose level every
five minutes for seventy-two hours and records
it in its internal memory.
Blood Sampling
Blood Sampling
GLUCOSE
MONITORIN
G DEVICES
Glucose Testing
GLUCOSE MONITORING DEVICES
GLUCOSE MONITORING DEVICES
GLUCOSE MONITORING DEVICES
GLUCOSE MONITORING DEVICES
Insulin pen injectors
Insulin jet injector
An insulin jet injector uses high-pressure air to send a fine
spray of insulin under your skin. This device may be an
option if you can't use needles....
INSULIN
DELIVERY
DEVICES
INSULIN DELIVERY DEVICES
INSULIN
DELIVERY
DEVICE
Site of Insulin Injection
Insulin is best injected into any area of
the body where fatty tissue is present
and where large blood vessels, nerves
and bones are not close to the surface .
Site of Insulin injection
Subcutaneous injection sites
INSULIN DELIVERY DEVICES
Spray Device (By Inhalation)