0 30 60 90 120 150

Fig. 11.1 Plasma [glucose] changes in response to an oral glucose tolerance test. The shaded
area indicates the approximate limits within which responses to a 75 g load of anhydrous
glucose normally fall.
Glucose can be detected in urine specimens collected after the renal threshold for glucose
has been exceeded; the normal threshold corresponds to a plasma [glucose] of 10 mmol/L, and
the lowered threshold in patients with renal glucosuria to a lower level of plasma [glucose]. The
various responses to the glucose tolerance test are described in greater detail in the text
Oral glucose tolerance test (GTT) (Fig. 11.1)
The main value of a GTT is that it may help to establish the
diagnosis of diabetes mellitus or impaired glucose tolerance at
a time when the metabolic abnormality is mild. The GTT is
particularly valuable in the diagnosis of impaired glucose
tolerance in pregnancy (p. 316). Several precautions must be
observed in prepar­ing for and in performing the test.
Before the test
It should not be performed on patients who are suffering from
the effects of trauma or recovering from a serious illness. It
should also be delayed if the patient has an intercurrent
infection. Drugs such as corticosteroids and diuretics may
impair glucose tolerance; they should be stopped before the
test, if possible

The patient should have been on an unrestricted diet

containing at least 150 g carbohydrate/day for at least 3 days,
and should not have indulged in unaccus­tomed amounts of
exercise. The patient must not smoke on the day of the test,
either: before or during the test, nor eat or drink anything
other than as specified
below.
Performing the test
A GTT is usually performed after an overnight fast,
although a fast of 4­5 hours mad, be enough. The patient is
allowed to drink water during the fast, and may have a cup of
unsweetened tea before the test; this helps to reduce any
tendency to nausea that might otherwise be caused by the oral
glucose drink.

A standard dose of glucose (82.5 g glucose monohydrate

or 75 g anhydrous glucose) dissolved in 250­350 mL of water,
lemon­flavoured or chilled (or both) to avoid nausea, is given
by mouth. Smaller amounts of glucose (1.92 g glucose
monohydrate or 1.75 g anhydrous glucose/kg body weight)
should be given to children or small adults to a maximum dose
of 82.5 g glucose monohydrate or 75 g anhydrous glucose.

During the test the patient should be sitting up, or lying

over on the right side so as to facilitate rapid emptying of the
stomach, not lying flat or over on the left side.
 Blood specimens are collected before giving the glucose
load, and thereafter (in a full GTT) at 30­minute intervals for 2
hours. In terms of the WHO criteria for tests performed on
patients with symptoms, it is only necessary to collect fasting
;and 2­hour post­glucose specimens. However, having decided
to perform the test, it is advisable to collect a full set of blood
specimens. They are needed for making the diagnosis of renal
glucosuria (see below), and for the recognition of abnor­mally
shaped GTT responses (e.g. lag­storage' curve). In cases of
suspected reactive hypoglycemia, it may be worthwhile to
prolong the blood collections until 6 hours after the dose of
glucose.

Urine specimens should be collected before the test and

at 1 and 2 hours after the dose of glucose; they should be
tested for glucose by 'side­room' tests (Table 2.2, p. 13).
Although the results for these urine measurements are not
included among the WHO diagnostic criteria for diabetes
mellitus, urine needs to be tested if patients with renal
glucosuria are to be recognized.
Abnormal GTT not associated with increased risk of diabetes
`Flat response' to GTT describes the response when the plasma
[glucose] fails to rise significantly. If the fasting plasma [glucose] was
5.0 mmol/L, the 30­minute and 60­minute or 60­minute and 90­minute
specimens, or all three specimens, would normally have a value of 7.0
mmol/L or more in a GTT. A 'flat response' is often caused by incorrect
positioning of the patient during the test, resulting in delayed gastric
emptying. It is occasionally due to intestinal malabsorptive disease; it
may also occur in hypopituitarism and in adrenal hyposecretory states.

lag-storage' response to GTT describes the pattern of results in

which there is a sharp rise in plasma [glucose], with the peak value
appearing early and sometimes exceeding 11.0 mmol/L. There is also a
tendency for the 2­hour value

to be much lower than the fasting value. There may be

glucosuria. This pattern of response is due to rapid absorption
of glucose from the intestine; the tissues, mainly the liver, are
unable to attain a sufficiently rapid uptake to match the rapid
absorption. It may be seen after gastric surgery (e.g.
gastroenterostomy) or in patients with severe liver disease,
and is sometimes seen in apparently healthy individuals.
 Renal glucosuria is the term applied to patients who
exhibit glucosuria at some point in the GTT although the
plasma [glucose] at all times remains below 10.0 mmol/L. It
is due to a lowered renal threshold for glucose, and usually
has no pathological significance. However, it may be
associated with other renal tubular defects (e.g. Fanconi
syndrome, p. 134).
Classification of diabetes mellitus
Clinically, patients with diabetes melli tus may be classified as
idiopathic (primary or essential) or as secondary diabetes.
There are other groups of patients in whom abnormalities of
glucose tolerance may be detected, but who do not fit into
either of these categories (see above).
Idiopathic diabetes
This may be caused by factors in the blood which antagonize
or inhibit the action ot insulin, or by the production of an
abnormal form of insulin, or by inability of the pancreas to
produce sufficient insulin from the earliest stages of the
disease. It Is divided into types 1 and II.
Insulin-dependent diabetes (type I)

In these patients there is defective insulin secretion. The condition usually

presents acutely in young (under 30) non-obese subjects, but it can
occur at any age. In addition to polyuria, thirst and glucosuria, there is
often marked weight loss E,r1cl ketoacidosis. In general, insulin is
required for treatment. The condition is sonic,- times subdivided into
types la and Ib.

Islet cell antibodies that react specifically with the [3-cells of the
pancreas have been demonstrated in serum from over 90% of patients
with newly diagnosed type Ia diabetes; over the subsequent few years,
these antibodies usually disappear. They have also sometimes been
demonstrated in serum several years before clinical and biochemical
features of diabetes develop. Individuals with certain human leucocyte
antigens (HLA) have also been shown to have a particularly high risk of
developing type la diabetes. The importance of these immunological
findings is in their application to relatives of diabetic patients. If a
sibling has islet cell antibodies, or HLA characteristics identical with the
patient's, the sibling is potentially diabetic and has an increased
probability of developing impaired glucose tolerance or frank diabetes
mellitus.
 Type lb patients show persistent islet cell antibodies and their
diabetes mellitus shows a clear association with other forms of auto-
immune endocrine disease. The age of presentation is, on average,
older than for the type Ia patients.

Non-insulin-dependent diabetes (type II)

This condition may be subdivided into obese and non-obese categories.

It generally

Present in older (over 40) patients who are obese, a condition that used to be
called`maturity onset' diabetes; it usually presents less,acutely than type I
diabetes. type II diabetes occurs in young patients.
Measurable levels of insulin are normally present, and the metabolic defect
awears to lie either in defective insulin secretion or in insulin resistance. Insulin
levels tend to be lower in the non-obese type II patient. In general, insulin is not
eciiiired for the prevention of ketosis as these patients are relatively resistant to
its ,1(welopment. However, insulin may be needed to correct abnormalities of
blood {glucose}
There appears to be no association between type H diabetes and either the
HLA system or the development of auto-immunity. However, there is a strong
c;c1 ietic element to the disorder. For instance, if one identical twin develops type
II diabetes,Thetes, there is a high probability that the other twin will develop it.
 Secondary diabetes

This occurs as a consequence of other diseases,

either pancreatic or endocrine. With pancreatic
diabetes, the secretion of insulin is reduced due to
pancreatitis,
I kwrnochromatosis or resection of the pancreas. In
diabetes secondary to other e!idocrine disorders,
ineffective insulin action is caused by abnormal
secretion of hormones with 'cliabetogenic' activity.
Several drugs adversely affect glucose i ol,:rance and
secondary diabetes may also occur in a number of
genetic disorders.

Table 11.4 summarizes the different causes.

Gestational diabetes mellitus

Impaired glucose tolerance and hyperglycaemia in

pregnancy are associated with ,)1) increased incidence of
fetal macrosomia and neonatal hypoglycaemia. In
ao,dbUobo6d\aboticpat\outnwhobocomoprognunt.poncb|
oodO\ucooecontro\\x 6L,,;ociated with a higher incidence of
intra-uterine death and fetal malformation. If h,lown diabetic
patient becomes pregnant, it is very important to maintain
close control of blood [glucose].

Gestational diabetes mellitus is the term used to describe

the abnormal glucose tolerance or diabetes mellitus that may
develop during pregnancy; in the majority of these cases, the
response to a GTT reverts to normal after the pregnancy but
about 50% of cases go on to develop diabetes mellitus later,
within
Table 11.4 Examples of causes of secondary diabetes or of
impaired glucosetolerance

Category of cause Examples

Drugs Oestrogen­containing oral
contraceptives, salbutamol
and some other
catecholarninergic drugs,
thiazide diuretics
Endocrine disorders Acromegaly, Cushing's
syndrome and Cushing's
disease, glucagonoma,
phaeochromocytoma,
prolactinoma, thyrotoxicosis
((occasionally
Insulin receptor Auto­immune insulin receptor
abnormalities antibodies, congenital
lipodystrophy
Pancreatic disease Chronic pancreatitis,
haemochromatosis,
pancreatectomy
 the next 7 years. When investigating a pregnant woman, the normal
criteria for interpreting the oral GTT should be used (see above). Mild
abnormalities should be reassessed not less than 6 weeks after
delivery.

Since the diagnosis of gestational diabetes mellitus is made on

the basis of an oral GTT, the question arises as to who should be
selected for this investigation Glucosuria detected at routine antenatal
testing may suggest the need for an oi al GTT, but it may have no
significance since the renal threshold for glucose tends to be lowered
in pregnancy. One approach is to select women with appropriate risk
factors, such as a family history of diabetes mellitus, a previous large
baby, unexplained stillbirth, etc. Also, glucosuria is more significant if
detected on the second specimen of urine passed after an overnight
fast (i.e. the first specimen passed is discarded), and this can be used
to select patients. Even normal women tend to show slightly impaired
glucose tolerance in pregnancy; this is especially true in the third
trimester.

There may be lactosuria late in pregnancy, usually detected by 'side-tests

for reducing substances (p. 14). It is readily distinguishable from
glucosuria and has no pathological significance.
Monitoring the treatment of diabetic patients

The frequency with which blood or plasma [glucose] needs to be

measured depends on each patient's diabetic characteristics. During
initial stabilization on insulin in hospital, 5-10 determinations may be
required each day. Thereafter, with type I diabetics at home, it may be
advisable for fasting blood [glucose] to he measured daily, to monitor
blood [glucose] before and after each main me& on one mid-week and
one weekend day, and to measure one post-prandial blood [glucose] on
other days; the closeness of monitoring needed depends on the
'brittleness' of the diabetes. Much less frequent monitoring is needed in
type II diabetics. Indeed, many older patients may be advised to
continue on a urine testing regime.

The use of simple chemical 'side-room' tests by patients testing their own
urine specimens regularly for glucose and ketone bodies (p. 13, Table 2.2),
recording the results, and in some cases adjusting their treatment on the basis of
the glucose results, had been standard practice for many years before home-
monitoring of blood [glucose] was introduced. Proper control of diabetes mellitus
is essential if long-term complications are to be avoided or their onset delayed.
As a result of developments in methods for blood [glucose] measurement (p. 17),
their use in home-monitoring now provides a practical and preferable alternative
to urine testing. Nevertheless, many diabetic patients continue to achieve good
control using only urine testing to monitor and regulate their treatment.
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