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‫بسم هللا الرحمن الرحيم‬
Faculty of Medicine
Alexandria University
Diabetes Unit &
Clinical Pathology&
Biochemistry
Departments
Clinical Scenario
Prepared by
Staff members of Diabetes, Metabolism &
Clinical pathology and Biochemistry
Departments
Faculty of Medicine
Alexandria University
By the end of this ILA session , the students will be able
to:
1-Recognize the clinical features of a common health
problem among the Egyptian population, which results
primarily from disturbance in the metabolism of Glucose
2-Apply the basic biomedical sciences studied in module
II to explain the clinical features of these diseases.
3-Identify the relation between some of the common
laboratory investigations used in diagnosis of the
condition and the biochemical structures and processes
already studied.
Clinical Scenario
Hoda is 48 years old lady with no family history of any
serious conditions, except her father has diabetes
mellitus.
In the past few weeks, she had been experiencing
increased urination, day & night, unusual thirst, and she
started to feel weak and tired more rapidly than usual.
Although she was eating more than usual, she now was
losing weight .
Hoda went to the primary health care
doctor in her territory. The primary
health care doctor took proper history
from Hoda, and did complete physical
examination.
The doctor confirmed from the history
that Hoda has now increasing urination ,
thirst , and loss of weight although she
was feeling more hungry and eating
more food
The doctor also asked about the previous
history of any diseases as well as the social
status and habits
Past History:
•Appendectomy in 1992. No chronic illnesses.
Social History and Habits:
•Hoda is a house wife, she has 3 grown up children.
•During the last few years, she spent most of her time watching TV
& chatting with friends over the phone
•She takes no medications, nutritional supplements or herbal
remedies.
Physical Examination
•Pulse
:
76 beats/min. (regular)
•Blood pressure
:
140/80 mm/Hg.
•Body weight
:
98.5 kg.
•Height
:
1.6 m
•The rest of the examination including : Head and neck , Chest,
abdomen and CNS were normal.
Assess the anthropometric measures using what
you learnt in nutrition
module
The doctor did a bedside test and said:
Mrs. Hoda: The test result is abnormal
and you will need some more
investigations
1. Which of the following laboratory
tests has the doctor conducted?
• Stool analysis.
• Urine analysis.
• Complete blood count
Urine samples used for detection of glucose
1- Early morning sample:
The first sample the patient produces on waking up.
It is a concentrated sample, therefore it is suitable for
detection of glucose.
2- Random sample:
A sample produced at any time during the day.
Disadvantage: The kidney varies the composition of urine
during the day according to water, salt & protein intake as
well as metabolic status. Therefore this sample may be
diluted and not very reliable.
It gives a good positive but a poor negative test.
Urine Reagent
Strips
Plastic strips containing dry reagents required for the
enzymatic detection of glucose.
In presence of glucose in the sample, a colour develops and its
intensity changes according to the amount of glucose present.
The strip is dipped briefly in urine. After 30 seconds,
the colour which develops on the test strip is compared
to the colours on the chart present on the box of strips.
The matching colour is taken as the correct
result.
Clinical Scenario
The doctor told her that the
urine sample contains 3+
glucose which is not a normal
finding . He said : We need to
find out why there is glucose in
the urine so we need to check
your blood glucose level
Urine strips are specific for glucose, i.e. they do not
give a colour reaction with any substance except
glucose.
However, this is not an accurate quantitative test,
In addition, people with high blood glucose levels
may have a high renal sugar threshold and
therefore glucose may not be excreted in urine
Random Blood Glucose
If you take the sample in the clinic by your self , then
you should sent it immediately to the lab and test
should be done done as quickly as possible . Otherwise,
glucose level in the sample will decrease due to
glycolysis which continues in vitro ( in the blood of the
patient while outside his body) .
We can collect the blood sample of the patient in
specific Tubes containing sodium fluoride which helps
to inhibit glycolysis and preserve glucose.
Floride Tubes
Plain Tubes
After the doctor received this Glucose
measurement he told Mrs Hoda that the
result is high and this might mean that
she has a common disease called
Diabetes mellitus.
He continued : thus ,we need to confirm the
diagnosis.
So ,I want you to go home , take your
dinner at 10 pm , do not eat or drink any
thing afterwards except enough water
(water contains no calories).
Then go to the lab at 8 am for other
measurements
Hoda went to the lab next day morning
with the following request :
•Fasting blood glucose
•2 hours post oral glucose load test
Fasting Plasma Glucose
Blood sample for fasting plasma glucose is
obtained after 8-12 hours fasting.
The patient should drink water freely during this
period so as to be well hydrated.
Glucose load: 75 grams glucose dissolved in 300
mL water.The patient drinks this over a period of
5 minutes.
A blood sample is taken 2 hours later.
Laboratory results for Mrs. Hoda :
•Fasting plasma glucose: 194 mg/dL.
Reference range : 70 – <100 mg/dL
•2-hours post load plasma glucose: 266 mg/dL.
Reference Range : less than 140 mg/dL
Hoda went back to the treating Doctor
with the results.
He told her that the results confirmed
that she has diabetes and he started
to explain the disease
The doctor explained to Hoda that the diagnosis of
diabetes mellitus is based on symptoms of
hyperglycemia like what she has, plus the results of
blood glucose tests: The laboratory results which
make the doctor suspect diabetes are:
• Fasting plasma glucose ≥ 126mg/dl
• 2-h post oral glucose load test: blood glucose
≥ 200 mg/dl .
• Random plasma glucose ≥ 200 mg/dl.
Note to the Physician:
If one of these tests is positive, it
must be confirmed by another
positive test on the subsequent day
in order to diagnose diabetes
mellitus.
1.What is hyperglycemia?
2.Why was there Hyperglycemia in this patient?
3.Explain why there is increased urination (polyuria)
with this high blood glucose?
4.Why Hoda had increased appetite (polyphagia)
despite high glucose levels?
5.Discuss normal glucose metabolism
6.Suggest the possible alterations in glucose storage
and break down that might occur in this clinical
problem .

1.
2.

A.
B.
C.
D.
INSULIN DEFICIENCY:
decreases uptake of glucose by cells.
insulin dependent enzymes are less active
Net effect:
inhibition of glycolysis
Inhibition of glycogenesis (glycogen
synthesis)
stimulation of gluconeogenesis
Stimulation of glycogenolysis (glycogen
degradation)
INSULIN
Glucose uptake
by the tissues
GLUCAGON
Breakdown of
tissue proteins
Glycogenolysis
Gluconeogenesis
Hepatic output
Of glucose
HYPERGLYCEMIA

Explain why there is increased urination
(polyuria) with this high blood glucose?

When the blood glucose levels exceed the renal
sugar threshold
glucose is excreted in
urine (glucosuria)

Due to the osmotic effect of glucose, more
water accompanies glucose excretion
Polyuria (increase in volume of urine excretion)
When the blood
glucose levels
exceed the renal
sugar threshold
glucose is excreted in
urine (glucosuria)
osmotic effect of
glucose
Polyuria
(increase in volume
of urine excretion)
water accompanies
glucose excretion

To compensate for the water loss

Thirst centre is stimulated

More water is is taken (polydepsia: always
thirsty, drinks a lot)

Why Hoda had increased appetite (polyphagia)
despite high glucose levels?

Although the blood glucose level is high but
glucose is not taken up by the cells due to
insulin deficiency therefore the cells are starved

The patient will take more food (polyphagia) to
compensate for the loss of glucose and also
loss of protein
Although the
blood glucose
level is high
BUT
BUT glucose is NOT
taken up by the cells
due to insulin
deficiency
the cells are starved
The patient will take more food (polyphagia)
to compensate for the decrease of glucose
and ATP intracellulary
Discuss normal glucose
metabolism
GLUCOSE
GLUCOSE
+
Insulin
glycolysis
+
Pyruvate
+
PDH
ACETYL COA
MITOCHONDRIA
CITRIC ACID
CYCLE
ATP
GLUCOSE -6- PHOSPHATE
1)OXIDATION
a) For energy
production
(glycolysis &
Krebs cycle)
b) For production
of pentose P
and NADPH (HMS)
2) Conversion to
other hexoses:
Fructose,
galactose
3)Conversion to
non essential
amino acids.
4)Storage in the
form of
glycogen or fats.
c) For production
of uronic acid.
Biological effects of insulin
PATHWAY Key
enzyme
Action of
insulin on the
enzyme
Glycolysis Glucokins Stimulation
dephosphorylation
e
of the enzymes
PFK-1
Pyruvate
kinase
Gluconeo- *Pyruvate
Inhibition
carboxylase
genesis
*PEPCK
*F1,6
diphosphatas
e
*Glucose 6
phosphatase
Dephosphorylation
of the enzymes
Direct Overall
effect effect
Hypoglycemia
Hypoglycemia
Biological effects of insulin
PATHWAY Key
enzyme
Action of
insulin on
the enzyme
Glycogen
synthesis
Activation
Glycogen
synthase
Direct
effect
Glycoge
dephosphorylatio n
storage
n
Overall
effect
Hypoglycemia
of the enzymes
Glycogen
degradation
Glycogen
phosphorylas
e
Glycoge
dephosphorylatio n
storage
n
Inactivation
of the enzymes
Hypoglycemia

In Diabetes Mellitus all these effects are
reversed because
INSULIN
A.
B.
C.
D.
GLUCAGON
inhibition of glycolysis
Inhibition of glycogenesis (glycogen
synthesis)
stimulation of gluconeogenesis
Stimulation of glycogenolysis (glycogen
degradation)

A.
B.
Suggest the possible alterations in glucose
storage and break down that might occur in
this clinical problem.
Inhibition of glycogenesis (glycogen
synthesis)
Stimulation of glycogenolysis (glycogen
degradation)
During digestion, food is broken down into
basic components, such as fatty acids from
lipids, amino acids from proteins and simple
sugars from carbohydrates.
All of these nutrients can be processed by of
the liver into one type of simple sugar,
glucose, which then enters the blood stream.
After digestion, glucose passes into the
bloodstream, where it is used by cells for
growth and energy.
For glucose to get into cells, insulin must be
present.
Insulin is a hormone produced by the
pancreas, a large gland behind the stomach.
When normal people eat, the pancreas
automatically produces the right amount of
insulin to move glucose from blood into our
cells.
In people with high blood glucose, when they
eat, the pancreas either produces little or no
insulin, or the cells do not respond
appropriately to the insulin produced (or both)
=> glucose builds up in the blood, overflows
into the urine, and passes out of the body in
urine => body loses its main source of fuel even
though blood contains large amounts of
glucose.
In the early stages of high blood glucose, there are no
symptoms until blood glucose levels exceed the "renal
threshold" and glucose appears in the urine.
When the "renal threshold" for glucose (a blood
glucose level of about 180 mg/dL), is exceeded for a
significant portion of the day, the patient will have the
classic symptoms of hyperglycemia: excessive
urination (polyuria) with consequent thirst and need
to keep drinking (polydipsia).
The loss of calories, due to the glucose loss in urine,
will lead to weight loss, and often a compensatory
increase in appetite (polyphagia).
The weight loss primarily is due to loss of muscle
mass with conversion of amino acids into glucose, as
a result of increase gluconeogenesis.
Persistent hyperglycemia can draw water into the eyes
and cause visual blurring.
Clinical Scenario
The doctor continued to talk to Hoda about
her illness. He said: Diabetes is very
common in Egypt. There are about 8 million
Egyptians that are diabetic, but a third of
them don’t know they have it. Egypt is one
of the top ten countries all over the world
that have large number of diabetics.
Your disease has some genetic predisposition.
But the main reasons that made it manifest is
the increased weight you had and the style of
life you were adopting in the last few years. You
were not doing any regular exercise and you
were living a sedentary life:
‫حياة مستقرة تتميز بقلة الحركة‬
This type of diabetes is easily controllable
through exercise, proper nutritional habits
and diet control , with weight loss. In
addition we might need to give a drug
called Hypoglycemic drug .
Can you explain how exercise, and
weight loss can help the diabetic
patient to control the high blood
glucose?
Diet:
Daily caloric intake:
 Carbohydrates : 50 – 60%
 Proteins
: 15 – 20%
 Fats
: 25 – 30%


Meals should be high in fibers and low in
simple sugars and saturated fats
Diet should be balanced, and distributed
throughout the day with the major 3 meals
and 2-3 snacks
Carbohydrates (CHO):
1- Simple CHO:

Sucrose, Honey, Jam, soft drinks, fruit
drinks
2- Complex CHO:

Rice, bread, cereals, dried beans, fruits,
vegetables, dentils and legumes.

•
•
•
Proteins
Examples: Lean meat, fish, chicken without
skin, milk, egg, & seafood.
Fish should be eaten more often and skin
should be removed from chicken.
Boiled foods are better than fried foods.
Fats

2 types: saturated & unsaturated:



a-Saturated fat: Solid at room temperature.
Examples: Butter, fat in meat and animal
products such as hamburger, cheese, coconut
oil, and palm oil
These should not exceed 7% of the total
energy from fat group.
b-Unsaturated fat:


Monounsaturated: Olive oil, Peanut oil
Polyunsaturated:
Soya
bean,
Corn,
Sunflower oils.
&

Exercise
•
Lowers blood sugar and
•
Increases sensitivity to insulin
•
Lowers blood pressure.
•
Helps to loose weight and maintain weight
•
Improves lipid profile



Aerobic exercise (brisk walking) is generally
recommended
Exercise should be done regularly on daily
bases at 30 min/day at least 5 times a week
Start slowly and gradually increase the
amount of exercise