OSPE CASE DISCUSSION

Presenter – Dr. Salma Ahmed

Dept. of biochemistry
CASE 1.
Q. A 50 YEAR old male attended OPD with complaints of
passing large volume of urine at frequent intervals,
unusual thirst, overeating and a feeling of weight loss
for the past 3 months.
What is your provisional diagnosis? Justify your provisional
diagnosis.
 i
s

c
Answers o
m
m
The most probable diagnosis is Diabetes Mellitus
o
n
l
y (excessive urination), polydypsia
 The patient presents with polyuria
(increased thirst), polyphagia (increased
s
hunger) and weight loss.
 More water is excreted alongwithe glucose (glucosuria) due to
osmotic effect (polyuria). To compensate
e for the excess water loss,
the thirst centre is activatted andnmore water has to be drunk
(polydypsia). To compensate the loss of glucose and protein, the
i
patient feels hungry and eat moren food (polyphagia).underutilization
of glucose leads to increased breakdown of fats and protein. This
results in loss of weight. i
n
d
i
Case 2.
Q. A 50 year old man comes to medicine opd with
complaints of increased hunger, thirst, and frequency of
urination. He also complains of tiredness, blurring of
vision and recent weight loss.
His lab tests showed-
 FBS- 180 mg/dl
 PPBS- 320 mg/dl
 Ketone bodies in urine – negative.
a) What is your probable diagnosis?
b) Comment on your diagnosis.
ANSWERS
• The patient presents with the classic symptoms of
polyuria, polydypsia, polyphagia , so the most probable
dignosis is DIABETES MELLITUS. His FBS≥126 mg/dl and
PPBS≥200 mg/dl which falls under the criteria for
diagnosis of Diabetes Mellitus (AMERICAN DIABETIC
ASSOCIATION)
CRITERIA FOR DIAGNOSIS OF DIABETES
MELLITUS (ADA,2014)
IMPAIRED GLUCOSE HOMEOSTASIS (PREDIABETES):
 Impaired fasting glucose : 100-125 mg/dl.
 Impaired glucose tolerance : (2 hour plasma glucose in the 75
gm OGTT): 140-199 mg/dl.
 Glycated hemoglobin (HBA1C): 5.7-6.4%.
• DIABETES MELLITUS:
 Classic symptoms of diabetes (polyuria, polydypsia, polyphagia
and weight loss ) and RBS > 200 mg/dl.
 FPG≥126 mg/dl.
 2 hour PG ≥200mg/dl during OGTT
 HBA1C≥6.5.
Case 3.
Q. A 75 years old senior citizen came to Medicine opd for a
routine check up. Following are his laboratory findings:
 Urine dipstick test for glucose – positive.
 random blood glucose – 138mg/dl
From the above findings give your provisional diagnosis.
Which test you will advise further.
Answer
The most probable diagnosis is Renal glycosuria.

 The patient doesnot present with the classic symptoms of

Diabetes and random blood sugar (RBS) is less than 200
mg/dl.
 Glycosuria occurs when the glucose concentration in the
blood rises beyond the renal threshold level (usually 180
mg/dl)
 In certain individuals , glycosuria is seen even when the glucose
concentration in the blood is well within normal limits.
Answer
 In persons with low renal threshold , glucose appears in
urine and such condition is known as renal glycosuria.
 In such cases glomerular filtration rate (GFR) is normal
but tubular reabsorbtion is decreased.

Patient to be advised to check fasting blood sugar(FBS),

post prandial blood sugar (PPBS) or glucose tolerance
test to further confirm the diagnosis.
Short overview of DIABETES MELLITUS
Metabolic disorder resulting either from deficiency of
insulin or resistance to its action causing
hyperglycemia which lead to several systemic
complications.

Can be classified into – type 1 and type 2 DM.

About 5% of type 2 DM cases occur due to single defects
(glucokinase gene on chromosome 7p) of pancreatic beta cell
function at a relatively younger age and are known as maturity onset
diabetes of the young (MODY).

 METABOLIC SYNDROME: It is an associated condition with

diabetes which is fast growing among the urban middle class
population and is characterized by insulin resistance associated with
obesity. The affected person cannot effectively use glucose despite
normal insulin levels.it is usually associated with a sedentery
lifestyle, alcoholism, elevated TAG levels, low HDL levels,
hyperuricemia, microalbuminuria, hypertension, polycystic ovarian
diasease.
METABOLIC ABNORMALITIES IN DIABETES
A) CARBOHYDRATE METABOLISM:
 Insulin deficiency/ resistance results in decreased
glucose uptake and underutilization of glucose by
cells.
 All the enzymes dependent on insulin become less
active;glycolysis and glycogenesis are decreased while
glycogenolysis and gluconeogenesis is increased.
 Net result is hyperglycemia; and when glucose level
crosses the renal threshold, it spills into urine
(glycosuria).
B)LIPID METABOLISM:
• Underutilization of glucose leads to increased utilization of
fatty acids forming more acetyl coA that can be handeled by
krebs cycle.
• Further increased gluconeogenesis depletes oxaloacetate, the
avalability of OAA to start TCA cycle is limited.
• Excess of acetyl coA is diverted for the synthesis of ketone
bodies resulting in ketoacidosis.conversion of fatty acvids to
TAG and secretion of VLDL from the liver are increased
leading to hyperlipidemia and fatty liver.
• Cholesterol levels in plasma are also elevated.
C) PROTEIN METABOLISM:
Protein breakdown is increased causing muscle
wasting.
Amino acids formed from protein breakdown are used
as substrates for gluconeogenesis.
Laboratory diagnosis and monitoring of
Diabetes Mellitus
1) Blood glucose estimation:
 Blood sugar estimated at any time of the day without any
prior preparations is known as Random Blood Sugar
(RBS).
 Sugar estimated in the morning before breakfast
after an overnight fast of 10-14 hrs is called Fasting Blood
Sugar (FBS).
 The analysis done at two hours after a meal
is called post lunch or post-prandial (prandial in Latin
means after food) Blood Sugar (PLBS or PPBS).
Determination of glucose in body fluids
The blood is collected using an anticoagulant
(potassium oxalate) and an inhibitor of glycolysis
(sodium fluoride). Plasma is separated for glucose
estimation.
Fluoride inhibits the enzyme, enolase, and so
glycolysis on the whole is inhibited. If fluoride is not
added, cells will utilize glucose and false low value may
be obtained. Capillary blood from fingertips may also
be used for glucose estimation by strip method. Modern
techniques use serum samples also.
Enzymatic method
Enzymatic Method
This is highly specific, giving ‘true glucose' values (fasting70-110
mg/dl ). Present day autoanalyzers can use only the enzymatic
methods.The glucose oxidase (GOD) method is the one most
widely used
 As a modification, the above GOD reaction mixture is
immobilized on a plastic film (dry analysis). One drop of blood
is placed over the reagent. The color is developed within one
minute. The intensity of dye is measured by reflectance
photometry. The instrument is named as glucometer. It is useful
for self monitoring of blood glucose (SMBG) by patients at home.But
the instrument is less accurate.
2. Urine testing for glucose, ketones and
proteins
Testing urine for glucose is commonly done in medical
wards by using glucose-specific dipsticks based on
Benedict's principle.
 Urine passed one-two hours after
a meal is preferred to a fasting sample.
However, apositive Benedict's test (glycosuria) itself is not
diagnostic because of individual variation in renal
threshold. Further, glycosuria is common during
pregnancy. However, glycosuria must always be further
investigated by blood testing for glucose levels both in
healthy individuals and in pregnant women (to rule out
gestational diabetes mellitus).
Detection of ketone bodies in urine is done by
Rothera's test. Ketonuria can be observed in normal
people who indulge in frequent fasting, doing strenuous
exercise for long periods or who have been on a high-fat
and low-carbohydrate diet. When ketonuria is
associatedwith glycosuria it indicates diabetes mellitus
that has been left untreated.
Testing for urinary albumin is performed to assess
renal damage. Excretion of >300 mg/day of albumin iş
diagnostic of diabetic nephropathy. When albumin is
excreted between 30 mg/day and 300 mg/day, the
condition is called microalbuminuria which indicates
that the person is at risk of developing diabetic
nephropathy. Diabetic patients must be checked for
microalbuminuria at least once a year. 
3. Blood lipids and other parameters
The concentrations of serum lipids-total cholesterol,
LDL and HDL cholesterol and triglycerides are done to
assess the metabolic status of diabetic patients.
Estimation of uricacid, homocysteine and lipoprotein
'a' in blood give valuable information about the
cardiovascular risk in diabetics.
4. Glucose tolerance test (GTT)
When signs and symptoms in a person are suggestive
of diabetes mellitus and the blood glucose values are
borderline, Glucose Tolerance Test (GTT) is performed
either to confirm or to exclude diabetes. The ability of
aperson to utilise a given quantity of glucose is known
as glucose tolerance.
5. Glycated hemoglobin
A diabetic patient on an oral hypoglycemic drug or on insulin
therapy is advised to undergo periodic monitoring of his
glycemic status (glucose concentration in blood) to assess the
efficacy of the treatment.
Non-enzymatic addition of a sugar to a protein is termed
glycation which occurs as a post-translational modification.
In persistent hyperglycemia, proteins undergo extensive
glycation. Among the glycated proteins, hemoglobin provides
reliable information regarding
hyperglycemia.
The glycation usually occurs on the HbA fraction of hemoglobin.
HbAlc constitutes most of the HbA1 fraction.
The concentration of HbAlc reflects the mean blood
glucose concentration of the preceding 8-10 weeks. This
corresponds to the lifespan of RBC (120 days),
where half of the erythrocytes are replaced in 60 days.
Hence, a single estimation of HbAlc gives quite a long-
term (about 2 months) picture of glycemic status.
When the level of HbAlc is less than 7% (equal to 154
mg/dl),the diabetic patient is considered to be
maintaining adequate control. Above 9% (corresponds to
212 mg/dl)indicates poor control. When the value of
HbAlc is between 5.7 and 6.5 the person can be diagnosed
as being in the stage of impaired glucose tolerance (pre-
diabetes).
6. Fructosamine
Apart from HbAlc, several other proteins are also
glycated.
 Glycated serum proteins are called(fructosamine) which
can also be measured along withHbAlc. Since albumin is
the predominant serumprotein, fructosamine levels
represent glycated albumin.
Half life of albumin is about 20 days and and hence
fructosamine gives a clue about the glucose level in the 3
weeks preceding its measurement.
Fructosamine estimation is particularly useful in
gestational diabetes mellitus.
Principles of management of diabetes
mellitus
Calorie restriction and moderate exercise.
Sugars with high glycemic index must be minimized in
diet.
Consumption of adequate amount of dietary fibres is
encouraged; low TAG, low cholesterol, low SFA, generous
amounts of PUFA and moderate amounts of proteins in
diet are suggested.
2 types of oral hypoglycemic drugs namely sulphonyl
ureas and biguanides are used for treatment of type 2DM.
INSULIN is the drug of choice for type 1 DM.