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

IX. Disorders of Carbohydrate Metabolism
67
to a maximum of 50% above the fasting level in 40 to
60 min and returns to the original level in 1½–2 h. The test
is performed by obtaining a fasting blood sample (0 time),
injecting 1 ml of 1:1000 epinephrine-HCL (in the dog)
intramuscularly and obtaining blood samples every 30 min
for 3 h.
The characteristic increase in blood glucose is used as
an index of the availability of liver glycogen for the production
of blood glucose. On the basis of a lowered response to
epinephrine, liver glycogen can indirectly be shown to be
depleted in bovine ketosis. This can be confirmed directly
by measurement of glycogen in biopsy samples. A lowered
glycemic response is also a characteristic response of the
glycogen storage diseases where glycogenolysis is inhibited
by enzyme deficiencies.
5 . Leucine-Induced Hypoglycemia
The oral administration of L-leucine induces a marked and
persistent hypoglycemia in hyperinsulinism because of pancreatic
islet cell tumors. The hypoglycemia is associated
with a rise in plasma insulin because of increased release
of insulin by the tumorous islet cells. The test is performed
by the oral administration of 150 mg L-leucine/kg
body weight as an aqueous suspension to the fasting dog.
A fasting blood glucose sample is taken before administration
(0 time) and every 30 min for 6 h. A hypoglycemic
effect is seen quickly at 30 min to 1 h and may persist for
as long as 6 h in hyperinsulinism. The normal dog exhibits
no hypoglycemic effect.
6 . Tolbutamide Test
The intravenous administration of tolbutamide, an oral
hypoglycemic agent, induces the release of insulin from
the pancreas and is used as a test of the availability of insulin
from the pancreas. The blood glucose curve during the
test parallels the insulin tolerance test. This test has not
been used in animals.
D . Ketone Bodies
The methodology and role of ketone bodies in the
carbohydrate economy of animals in health and disease
are discussed in the chapter on lipid metabolism. The
major ketone bodies are acetone, acetoacetate (AcAc),
and 3-OH-butyrate (3-OH-B). The 3-OH-B is the precursor
of acetone and AcAc so that the measurement of any
or all in body fluids is a standard method to evaluate ketosis
and ketoacidosis. Additionally, 3-OH-B constitutes half
or more of the total ketone bodies. The quantitative assay
for 3-OH-B is based on the use of the enzyme 3-OH-B
dehydrogenase (3-OHB-D). A point-of-care enzymatic and
colorimetric method for the assay of plasma 3-OH-B is
based on the enzyme 3-OH-B-D and nitroblue tetrazolium
(NBT):
3-OH-BD
3-OH-butyrate NAD
→ acetoacetate
NADH
H
diaphorase
NADH NBT(ox) → NAD NBT (red)
IX . DISORDERS OF CARBOHYDRATE
METABOLISM
Although alterations in blood glucose levels occur in a
wide variety of disease states, they are of particular importance
in the endocrine disorders. Normal blood glucose levels
are the result of a finely balanced system of hormonal
interaction affecting the mechanisms of supply and removal
from the circulation. When a hormonal imbalance occurs,
a new equilibrium is established. Whether this equilibrium
is clinically evident as a persistent hypoglycemia or hyperglycemia
depends on the total interaction of the hormonal
influences on carbohydrate metabolism. Further discussions
concerning the disorders of the pituitary, adrenals,
and the thyroids are presented in their respective chapters.
The following sections discuss the conditions in which the
principal manifestations are closely related to derangements
in carbohydrate metabolisms.
A . Diabetes Mellitus
Although diabetes mellitus has been reported in virtually
all laboratory animals (gerbils, guinea pigs, hamsters, mice,
rats, nonhuman primates) and in horses, cattle, sheep, and
pigs, it is most frequently found in dogs and cats. Estimates
of the incidence of diabetes range as high as 1:66 (1.52%)
for dogs and 1:800 for cats. Diabetes mellitus in animals
has been frequently reviewed ( Engerman and Kramer,
1982 ; Kaneko and Howard, 1989 ) .
1 . Natural History of Diabetes
The disease in dogs occurs most frequently in the mature
or older female, often in association with estrus and in all
breeds. In contrast, male cats appear to be more commonly
affected than females. In the dog, it is frequently associated
with obesity and it is now known that obesity is the single
most important contributing factor to the development of
diabetes ( Mattheeuws et al ., 1984 ). In the obese cat, the
GTT is significantly impaired, suggesting that obesity also
predisposes cats to diabetes ( Nelson et al ., 1990 ). The obese
cat also has a GST response like that of the type II diabetic
(Kirk et al ., 1993 ). Little is known of the genetic aspects
of diabetes in animals as compared to humans in which the