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

IX. Disorders of Carbohydrate Metabolism
73
The ketone bodies are very low renal threshold substances,
and their appearance in the urine is an early and
significant sign of developing ketonemia and acidosis.
They are not, however, diagnostic of diabetes because ketonuria
is observed in starvation or any form of increased fat
catabolism. Ketonuria is also absent in mild diabetes, but
ketonurias of varying degrees are common in the advanced
diabetic state. Therefore, ketonurias can be useful for prognostication.
Generally, the type I diabetic is prone to ketonuria
because there is an absence of insulin. In the type II
diabetic, ketonuria occurs less frequently because there is
ample insulin and ketonuria is seen only when the diabetes
has advanced to the point of complete failure of production.
Urine pH is of little value in detecting acidosis because
only in extreme cases does the pH reflect acidosis.
11 . Summary
The alterations in blood plasma that have been described
are summarized in Figure 3-16 . In the diabetic state, the
uptake and hence utilization of glucose by muscle and adipose
tissue is depressed. In these tissues, protein and lipid
breakdown is enhanced, and increased amounts of their
constituent amino acids and fatty acids are released to the
circulation and carried to the liver. Increased hepatic urea
G-6-P
pyruvate
Amino
acids
MUSCLE
glucose
G-6-P
glycogen
AC
glycogen
Lactate
CO 2
amino acids
PEP
glucose
circulation
Increases: glucose
ketone bodies
cholesterol
urea
lipids, FFA
fatty acids
urea
LIVER
Pyruvate
G-6-P
ADIPOSE
triglyceride
Ac
fatty acid
fatty acid
ketone bodies cholesterol
CO 2
FIGURE 3-16 Summary of metabolic alternations in tissues of major
importance in the diabetic animal. Increased flow in the metabolic pathways
is noted by larger arrows. FFA free fatty acids.
production results from the catabolism of these amino
acids. Increases in the key gluconeogenic enzymes of the
liver, G-6-Pase, PEP-CK, and PC direct glucose metabolism
toward an overproduction of glucose. Simultaneously,
lipogenesis is suppressed and with the increased mobilization
of fatty acids, AcCoA accumulates and is followed by
increased cholesterogenesis and ketogenesis. In the peripheral
tissues, there is an underutilization of ketones, all of
which results in a net increase in blood ketones and subsequent
ketoacidosis. Thus, diabetes mellitus is characterized
by a fundamental overproduction of and an underutilization
of both glucose and ketones as the result of the absolute
or relative deficiency of insulin.
B . Hyperinsulinism
After the discovery of insulin, a clinical state with marked
similarities to insulin overdosage was recognized as a disease
entity in humans and named hyperinsulinism. The disease
is now known to be due to a persistent hyperactivity
of the pancreas as the result of insulin secreting islet cell
tumors. Excess insulin can be extracted from metastatic
foci in liver as well as from the pancreatic tumor. There
are many reports on this disease in dogs ( Hill et al ., 1974 ;
Mattheeuws et al ., 1976 ). Priester (1974) and Kruth et al .
(1982) reviewed pancreatic islet cell tumors in animals in
the United States and Canada. In humans, more than 90%
of insulinomas are said to be benign, and in those active
tumors, complete surgical resection is required to effect a
cure ( deHerder, 2004 ).
Hyperinsulinism is characterized by a persistent hypoglycemia
with periods of weakness, apathy, fainting, and
during hypoglycemic crises, convulsions, and coma. A
history relating the attacks to periods after fasting or
exercise provides a clinical basis for further investigations.
Establishment of the diagnosis depends on finding
a hypoglycemia of 3 mmol/l ( 55 mg/dl) at the time of
symptoms and a hyperinsulinemia, usually 20 μ U/ml.
The symptoms are also relieved by glucose administration.
In mild cases, the fasting glucose level may be within
the reference range, in which case, diagnostic hypoglycemia
may be provoked by sequentially (1) placing on a low
carbohydrate diet (meat only) with frequent feedings for 1
week, (2) placing on a 24-hour fast, and finally (3) adding
moderate to stressful exercise (e.g., running on a lease
for 15min). Blood glucose is determined at the end of each
step, and if hypoglycemia is seen at any step, the provocation
should be terminated. Serum insulin is determined at
this time and a hyperinsulinemia is generally diagnostic of
insulinoma. Calculations of ratios—insulin/glucose, glucose/
insulin, amended insulin/glucose—do not offer any advantages
over the individual insulin and glucose values.
The glucose tolerance curve is generally characteristic
of an increased tolerance if the test is modified: (1) the dog