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2 hours
<7.8 <11.1 >11.1
after
(<140) (<200) (>200)
glucose
For conducting GTT in children, oral glucose is
given on the basis of weight (1.5 to 1.75 g/kg).
In case of pregnant women, 100 g oral
glucose is recommended.
Mini GTT carried out in some laboratories,
fasting and 2 hrs. sample (instead of 1/2 hr.
intervals) of blood & urine are collected.
To evaluate the glucose handling of the body
under physiological conditions, fasting blood
sample is drawn, the subject is allowed to
take heavy breakfast, blood samples are
collected at 1 hour & 2 hrs (post-prandial-
meaning after food).
Urine samples are also collected.
This type of test is commonly employed in
established diabetic patients for monitoring
the control.
For individuals with suspected malabsorption,
intravenous GTT is carried out.
Corticosteroid stressed GTT is employed to detect
latent diabetes.
Glycosuria:
The commonest cause of glucose excretion in urine
(glycosuria) is diabetes mellitus.
Glycosuria is the first line screening test for diabetes.
Normally, glucose does not appear in urine until the
plasma glucose concentration exceeds renal
threshold (180 mg/dl).
Renal glycosuria:
Renal glycosuria is a benign condition due to
a reduced renal threshold for glucose.
It is unrelated to diabetes & should not be
mistaken as diabetes.
Further, it is not accompanied by the classical
symptoms of diabetes.
Alimentary glycosuria:
In certain individuals, blood glucose level rises
rapidly after meals resulting in its spill over
into urine.
This condition is referred to as alimentary
glycosuria.
It is observed in some normal people & in
patients of hepatic diseases, hyperthyroidism
& peptic ulcer.
Hyperglycemia:
Elevation of blood glucose concentration is the
hallmark of uncontrolled diabetes.
Hyperglycemia is primarily due to reduced
glucose uptake by tissues & its increased
production via gluconeogenesis &
glycogenolys.
Glucose is excreted into urine (glycosuria).
Ketoacidosis:
Increased mobilization of fatty acids results
in overproduction of ketone bodies which
often leads to ketoacidosis.
Hypertriglyceridemia:
Conversion of fatty acids to TAGs & secretion
of VLDL & chylomicrons is higher in diabetics.
Plasma levels of VLDL, chylomicrans, TAGs &
cholesterol are increased.
Glycosuria – glucose excretion in urine.
Due to osmotic effect, more water
accompanies the glucose (polyuria).
To compensate for this loss of water, thirst
center is activated & more water is taken
(polydypsia).
To compensate the loss of glucose & protein,
patient will take more food (polyphagia).
Diabetic keto acidosis (DKA):
DKA more common in T1DM.
Normally the blood level of ketone bodies is
<1 mg/dl & only traces are excreted in urine.
Increased synthesis causes the accumulation
of ketone bodies in blood.
It causes ketonemia, ketonuria & smell of
acetone in breath.
Together constitute ketosis.
Detected by Rothera's test.
Supportive evidence may be derived from
estimation of serum electrolytes, acid–base
parameters & glucose estimation.
The urine of a patient with diabetic keto
acidosis will give positive Benedict's test as
well as Rothera's test.
But in starvation ketosis, Benedict's test is
negative, but Rothera's test will be positive.
Diabetes Mellitus:
The combination of hyperglycemia,
glucosuria, ketonuria & ketonemia is called
diabetic ketoacidosis (DKA).
Untreated diabetes mellitus is the most
common cause for ketosis.
Deficiency of insulin causes accelerated
lipolysis & more fatty acids are released into
circulation.
Oxidation of these fatty acids increases the
acetyl CoA pool.
Enhanced gluconeogenesis restricts the
oxidation of acetyl CoA by TCA cycle, since
availability of oxaloacetate is less.
In starvation, dietary supply of glucose is
decreased.
Available oxaloacetate is channelled to
gluconeogenesis.
The increased rate of lipolysis provides
excess acetyl CoA which is channeled to
ketone bodies.
The high glucagon favors ketogenesis.
Hyperemesis (vomiting) in early pregnancy may
also lead to starvation-like condition & may lead to
ketosis.
In both diabetes mellitus & starvation, the
oxaloacetate is channelled to gluconeogenesis.
Acetyl CoA cannot be fully oxidized in TCA cycle.
This excess acetyl CoA is channelled into ketogenic
pathway.
Metabolic acidosis:
Acetoacetate & β-hydroxy butyrate are
accumulated, causes metabolic acidosis.
There will be increased anion gap.
Reduced buffers:
The plasma bicarbonate is used up for
buffering of these acids.
Kussmaul's respiration:
Patients will have typical acidotic breathing due to
compensatory hyperventilation.
Smell of acetone in patient's breath.
Osmotic diuresis induced by ketonuria may lead to
dehydration.
Sodium loss:
The ketone bodies are excreted in urine as their
sodium salt, leading to loss of cations from the body.
High potassium:
Due to lowered uptake of potassium by cells
in the absence of insulin.
Dehydration:
Sodium loss further aggravates dehydration.
Coma:
Hypokalemia, dehydration & acidosis
contribute to the lethal effect of ketosis.
Parenteral administration of insulin & glucose.
Intravenous bicarbonate to correct acidosis.
Correction of water imbalance by normal
saline.
Correction of electrolyte imbalance.
Hyperglycemia is directly or indirectly
associated with several complications.
These include
Atherosclerosis
Retinopathy
Nephropathy
Neuropathy.
Dietary management:
A diabetic patient is advised to consume low
calories (i.e. low carbohydrate & fat), high
protein & fiber rich diet.
Diet control & exercise will help to a large
extent obese NIDDM patients.
Hypoglycemic drugs:
The oral hypoglycemic drugs are broadly of
two categories-sulfonylureas & biguanides.
Sulfonylurea such as acetohexamide,
tolbutamide & gibenclamide are frequently
used.
They promote the secretion of endogenous
insulin & help in reducing blood glucose level.
Management with insulin:
Two types of insulin preparations are
commercially available – short acting & long
acting.
The short acting insulins are unmodified &
their action lasts for about 6 hours.
The long acting insulins are modified ones &
act for several hours, which depends on the
type of preparation.
Glycated hemoglobin:
Refers to the glucose derived products of normal adult
hemoglobin (HbA).
Glycation is a post-translational, non-enzymatic
addition of sugar residue to amino acids of proteins.
Among the glycated hemoglobins, the most abundant
form is HbA1c.
HbA1c is produced by the condensation of glucose
with N-terminal valine of each β-chain of HbA.
The rate of synthesis of HbA1c is directly related to
the exposure of RBC to glucose.
The concentration of HbA1c serves as an indication of
the blood glucose concentration over a period.
HbA1c concentration is about 3-5%.
In diabetic patients, HbA1c is elevated (15%).
HbA1c reflects the mean blood glucose level over 2
months period prior to its measurement.
Other proteins in the blood are glycated.
Glycated serum proteins (fructosamine) can
also be measured in diabetics.
Albumin is the most abundant plasma
protein, glycated albumin largely contributes
to plasma fructosamine measurements.
Albumin has shorter half-life than Hb.
Glycated albumin represents glucose status
over 3 weeks prior to its determination.
Microalbuminuria is defined as the excretion of 30-
300 mg of albumin in urine per day.
Microalbuminuria represents an intermediary stage
between normal albumin excretion (2.5-30 mg/d) &
macroalbuminuria (>300 mg/d).
The small increase in albumin excretion predicts
impairment in renal function in diabetic patients.
It indicates reversible renal damage.
Textbook of Biochemistry – U Satyanarayana