1. Blood Glucose
• Normal Fasting Blood Glucose = 80 – 100 mg/dl
• Post-Prandial Blood Glucose = 100 – 120 mg/dl
mg/dl mmol/l
30 1.7
80 4.4
150 8.3
250 14.0
400 22.2

2. Sources of Blood Glucose
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

3. Factors Regulating Blood Glucose
1.Gastrointestinal tract factors
2.Hepatic factors (Glucostat organ)
3.Renal factors
4.Hormonal factors

4. Factors Regulating Blood Glucose
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

5. 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

6. 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

7. 4.Hormonal factors:
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

8. Glucagon Action on Cells
Endocrine response to hypoglycemia

10. 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

11. Gluconeogenesis
Lipolysis
Glycogenolysis

12. 3. Cortisol “Stress Hormone”
 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!

13. 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)

14. 5. ACTH
 ACTH stimulates the production
of glucocorticoids
 Glucocorticoids stimulate
gluconeogenesis

15. 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

16. 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

17. 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

18. 7. Insulin
• Circulating insulin
rapidly binds to
receptors on cell
surfaces, increases
glucose entry into
cells and alters
metabolic pathways
Fed-state metabolism

19. Action of
glucagon and
insulin on the
liver, muscle, and
adipose tissue.

21. Phases of Glucose Homeostasis
Nutritional Gluconeogenic
Well-Fed Post-absorptive Prolonged
Status (early)
Origin of Hepatic
Hepatic glycogen, Gluconeo-
Blood Exogenous glycogen,
Gluconeogenesis genesis
Glucose Gluconeogenesis
Tissues All except liver. Brain & RBC's; Brain
Using All Muscle, adipose Small amount by Slow rate;
Glucose diminished rates Muscle RBCs normal
Major Fuel
of the Glucose Glucose Glucose Ketone bodies
Brain

22. Fed Post absorptive Gluconeogenic Prolonged
40 Exogenous
(glucose
from diet)
Glucose Used g/hr
30 glucose from
gluconeogenesis
glucose from (lactate + amino acids) glucose from
20 liver glycogen gluconeogenesis
(mostly lactate)
10
0
4 8 12 16 2 7 42
HOURS DAYS
Sources of blood glucose in the various nutritional states

23. Summary of Blood Glucose Homeostasis
 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
 Under conditions where insulin levels are high, the
number of receptors declines and the target tissues
become less sensitive, resulting in “down regulation”

24. 22%
45%
Glucose Homeostasis

25. Blood Glucose, What’s “normal”?

28. 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

29. Role of
Pancreas in
Normalizing
Blood Between After high
carbohydrate diet
Glucose meals
Level

30. Distribution of Glucose After Meal

31. 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!

33. Insulin Synthesis

34. 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.

35. DNA coded information
inside the Nucleus
Transcribed RNA
Insulin
molecule
Transcription &
Translation of the
Insulin Protein
mRNA
tRNA
Ribosome

36. Tertiary
Structure
of Insulin

37. Preproinsulin
4
(21)
64 Lys
31 Arg 65 Arg 1
32 Arg
(24)
2
(30) Aids in transporting insulin
through the membrane
3
(35)
[Connecting peptide]

38. Aids in transporting insulin
through the membrane
Preproinsulin
Synthesized in Ribosomes

39. Proinsulin
In Endoplasmic Reticulum

40. Insulin
In Golgi Apparatus

41. Synthesized in Ribosomes
Leader
(Signal) chain
Post-translational
Processing of
Insulin
In Endoplasmic Reticulum
A chain 21 amino acids
In Golgi Apparatus
B chain 30 amino acids

42. Mechanism of Action of Insulin
Muscle

44. Mechanism of Action of Insulin
1. Increases peripheral tissue uptake (Fat, RBC’s
& Muscle cells)

46. NORMALLY IN THE BODY

47. 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)

48. 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)

49. Protein
synthesis
3 4
Lipogenesis
Glycogenesis Glycolysis
1
2

50. 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)

51. Oral Glucose Tolerance Test (OGTT)
Mild Moderate Severe Renal
No Parameter Normal
Diabetes Diabetes Diabetes Diabetes
Fasting
70 – 110 70 – 140 140 – 180 > 180 mg/dl 70 – 110
1 Blood
Glucose mg/dl mg/dl mg/dl mg/dl
Peak
2 Time
After 1 hr After 1 hr After 1 hr After 1 hr After 1 hr
Peak < 140 < 180 230 – 270
3 Value
> 270 mg/dl < 140 mg/dl
mg/dl mg/dl mg/dl
Time of
return to 2:30 – 4:00 4:00 – 5:00
4 Fasting
2:00 hr 2:30 hr 2:00 hr
hr hr
Level
Glucose Present in
Present in the Present in the
in
5 Urine
Absent Absent Middle of the all Middle of the
Samples Samples Samples
Samples

52. Oral Glucose Tolerance Test (OGTT)

53. Diabetes Mellitus
Prof. Dr.
Mamdouh El-Shishtawy

54. Diabetes Mellitus
 A medical disorder
characterized by hyperglycemia
(elevated blood glucose level)
especially after eating

55.  “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

56. Diabetes
 Disease in which the body:
 Does not produce insulin, or
 Does not properly use insulin

57. 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

58. Main Types of
Diabetes Mellitus (D.M.)
Type I (IDDM) Type II (NIDDM)
Insulin Dependent Non-Insulin
Diabetes Mellitus Dependent Diabetes
Mellitus

59. 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

60. Other Types of Diabetes Mellitus (D.M.)
• 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

63. Other Classes of D. M.
5. Diabetes insipidus:
due to deficiency of
Vasopressin (ADH)
 polyuria

64. 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

65. 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)

66. 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

67. 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)

68. Risk Factors for Diabetes Mellitus
2
1

69. 4 2
3 1

70. 9 10
7 8
5 6

71. High-Tech increases Body
Weight
Cellular phones and remote controls
deprive us from walking!
20 times daily x 20 m = 400 m
Walking distance lost/year
400x365 = 146,000 m
146 km = 25 h of walking
1 h of walking = 113-226 kcal
Energy saved =2800-6000 kcal
 0.4-0.8 kg adipose tissue
Rössner, 2002

72. Increased Time at Computer/TV/Video
Decreases Time for Leisure-Time
Physical Activity
>

73. New Remote Control
Can Be Operated by
Remote
• No more leaning
forward to get
remote from coffee
table means greater
convenience for TV
viewers
• Television watching became
even more convenient with
Sony’s introduction of a new
remote-controlled remote
control

74. Eat to
Live to Eat!
Live!

75. “EAT TO LIVE”
Intake = Expenditure
Weight Stable
“LIVE TO EAT”
Intake > Expenditure
Obese

77. reveals itself in childhood.
can be made worse from excessive lifestyle.

79. Type I (IDDM)
Insulin Dependent Diabetes
 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)

80. Type I (IDDM)
 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

83. Type I IDDM Lipid metabolism
Fatty acid production
Ketone formation
Decreased glucose
uptake & Protein
metabolism
Glycogenolysis
Gluconeogenesis
Decreased glucose
uptake

84. 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, ٌ ُ َ‫تن‬
‫َ ّفس‬
‫ُ ذي‬
ّ ِ ْ‫( )جه‬Kussmaul respirations)
 Loss of consciousness (rare)

85. Type II (NIDDM)
Non-Insulin Dependent Diabetes
 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

86. Type II (NIDDM)
 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

87. DIABETES TYPE 2:
INSULIN RESISTANCE

88. Type II (NIDDM)
 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

89. Type II Diabetes Mellitus
Decreased glucose
uptake with any
amount of insulin
Insulin resistance

90. Insulin Receptors

91. Insulin Resistant Cell

92. Insulin Shock
 People who accidentally take too much insulin
may be victims of insulin shock
 The symptoms of insulin shock include:
 Agitation ‫الهياج‬
 Trembling ‫اإلرتِعاد‬
 Sweating ‫ال َعَ ُق‬
‫ت ّر‬
 Pallor ‫الشحوب‬
 Speech difficulty ‫صعوبة الكالم‬
 Unconsciousness ‫فقذ الوعي‬

93. 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

94. 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 (‫ ) َمَل ؛ اِخْ ِرار‬or tingling
‫ذ‬ ‫ن‬
(‫ )نَخْز‬of the hands and feet
 Impotence or erectile dysfunction

95. Bases of Treatment of
Diabetes Mellitus

96. Type I (IDDM) 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”

97. Basis of Treatment of Type II (NIDDM)
 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

100. Diagnosis of Diabetes Mellitus
 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.

101. Criteria for 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

102. Hypoglycemia
 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

103.  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

104. Manifestation & Complication of Diabetes
1- Carbohydrate Disturbances
 Hyperglycemia
 Glucosuria
 Hyperphagia (eating too much)

105. Manifestation & Complication of Diabetes
2- Lipid Disturbances
 Hyperlipemia
 Fatty liver
 Ketonemia
 Ketoacidosis
 Ketonuria
 Coma

106. Manifestation & Complication of Diabetes
2- Lipid Disturbances (Cont.)
 Hypercholesterolemia
 Atherosclerosis
 Gangrene
 Amputation

107. Manifestation & Complication of Diabetes
3- Protein Disturbances
 Negative N2 balance
 Weakness & wasting of muscles

108. Manifestation & Complication of Diabetes
4- Water Disturbances
 Osmotic diuresis
 Polyuria
 Dehydration
 Polydepsia (Thirsty)

109. Manifestation & Complication of Diabetes
5- Pathological Changes
 Cataract
 Neuropathy
 Nephropathy
 Retinopathy
 Blindness

110. Diabetic
Complication

111. Diabetic
Complication

112. Diabetic
Complication

113. Diabetic Patients
• Diabetic Patients must examine feet
thoroughly, looking for blisters (‫,)بثور‬
cuts (‫ )تخفيضات‬and bruises (‫)كدمات‬

115. Don't miss a spot Diabetes can damage nerves
(neuropathy), reducing the ability
If you're unable to
to feel pain in your feet. That
see some parts of
means you may not notice a
your feet, use a small cut or blister until it
mirror. becomes a large sore.

116. • Athlete's foot is
Look for infection a common
fungal infection

117. Serious Complications

118. Serious Complications of
Chronic hyperglycemia

120. Chronic hyperglycemia
Gangrene of toes

121. Chronic hyperglycemia
Ophthalmoscope
Normal Diabetic retinopathy

125. Continuous Glucose Monitor &
Insulin Pump

127. Insulin
pump

128. 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.

129. Blood Sampling

130. Blood
Sampling

131. GLUCOSE
MONITORIN
G DEVICES

133. Glucose Testing

134. GLUCOSE MONITORING DEVICES

135. GLUCOSE MONITORING DEVICES

136. GLUCOSE MONITORING DEVICES

137. GLUCOSE MONITORING DEVICES

138. Insulin pen injectors

139. 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....

140. INSULIN
DELIVERY
DEVICES

141. INSULIN DELIVERY DEVICES

142. INSULIN
DELIVERY
DEVICE

143. 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 .

145. Site of Insulin injection

149. Subcutaneous injection sites

150. INSULIN DELIVERY DEVICES
Spray Device (By Inhalation)

152. Thank You