Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
PLASMA INSULIN (mu/ml)
75
50
25
Nsulin resfonse in diabetes mellitus of dogs
Type I
Type II
Type III
Normal
0
0
5 10 15 30
TIME (min)
The IVGTT and the insulin response are of greatest
value in the diagnosis of diabetes, particularly those cases
with a mild hyperglycemia and without persistent glucosuria.
Furthermore, the insulin response to the IVGTT
allows for the accurate differentiation of the different types
of diabetes. This has great significance because the type
II diabetic can potentially respond to oral hypoglycemic
therapy. Decreased tolerance is also observed, though less
consistently, in hyperthyroidism, hyperadrenalism, hyperpituitarism,
and in severe liver disease. An increased tolerance
is observed in hypofunction of the thyroids, adrenals,
pituitary, and in hyperinsulinism.
2 . Insulin Tolerance Test
45 60
FIGURE 3-14 The insulin response during the IVGTT in normal dogs
and in dogs with various types of diabetes mellitus. Key: ▲ type I; ❍,
type II; ●, type III; Δ normal ( Kaneko et al. , 1977 ).
The blood glucose response of a normal animal after the
administration of a test dose of insulin exhibits a characteristic
response as shown in Figure 3-15 . After obtaining a
fasting blood sample, 0.1 unit of crystalline zinc insulin per
kilogram body weight is injected intramuscularly or subcutaneously,
and blood samples are taken every 30 min for
3 hours. The test measures (1) the sensitivity of the blood
glucose level to a test dose of insulin and (2) the response
of the animal to the insulin-induced hypoglycemia.
Normally, the blood glucose level falls to 50% of its fasting
level in 20 to 30 min and returns to its fasting level in
1½ to 2 h. Two types of abnormal responses are seen. If the
blood glucose level does not fall by 50% or requires longer
than 30 min to reach the maximum hypoglycemic level,
the response is described as “ insulin insensitive ” or “ insulin
resistant. ” Insulin resistance is found, though inconsistently,
in hyperfunction of the pituitary and adrenals. This test has
not been used in the type II diabetic dog or cat but may be
of value in evaluating insulin resistance in this type.
If the hypoglycemia is prolonged and fails to return
to the fasting level in 2 h, the response is described as
FIGURE 3-15 Insulin tolerance in the dog. Curves falling in the shaded
areas are described as noted.
“ hypoglycemia unresponsiveness. ” This type of response
may be observed in hyperinsulinism, hypopituitarism, and
hypoadrenalism and is most often used in suspected cases
of the latter two diseases. An inability to secrete sufficient
glucagon by the pancreatic delta cells may also be a significant
factor in the unresponsiveness. In carrying out this
test, because a hypoglycemia is being induced, a glucose
solution should be readily available for injection.
3 . Glucagon Stimulation Test
Glucagon via hepatic glycogenolysis and gluconeogenesis
has a hyperglycemic effect, which in turn evokes an insulin
response. In addition, glucagon is an insulin secretagogue
second only to glucose. These are the bases for the
glucagon stimulation test (GST), which has been used for
the diagnosis of diabetes in cats ( Kirk et al ., 1993 ). The
test is performed by the I.V. injection of 30- μg glucagon/
kg body weight. Samples for blood glucose and insulin are
obtained before injection (0 time) and at 5, 10, 15, 30, 45,
and 60 min after injection. In cats, the peak insulin response
was observed at 15 min followed by a rapid decline to baseline
levels at 60 min. The insulin response curve was flat in
the type I diabetic cats whereas controls, obese, and type II
diabetic cats had comparable 15-min peaks and declines to
baseline at 60 min.
Samplings at half-hour intervals can be continued for
up to 3 hours in suspected hyperinsulinism. An exaggerated
15-min insulin response followed by a marked hypoglycemia
at 2 to 3 h or longer are characteristic of pancreatic
islet cell tumors ( Johnson and Atkins, 1977 ). However,
Kruth et al . (1982) found that the GST was not diagnostic
for these cases.
4 . Epinephrine Tolerance Test
Epinephrine also has a postinjection hyperglycemic effect
via hepatic glycogenolysis. The blood glucose level rises