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

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Chapter | 3 Carbohydrate Metabolism and Its Diseases
(HMF-TBA), reported a reference range of 1.4% to 3.2 %
HbA1c (2.3 1.96 SD). Previous assays for HbA1c have
been time, labor, and equipment intensive as well as giving
variable results. The colorimetric HMF-TBA method shows
promise of being a clinically viable method.
b . Fructosamine
The fructosamines (FrAm) reflect the average blood glucose
over the preceding 2 weeks in a manner analogous
to HbA1c. This means that FrAm could be used to monitor
the average blood glucose on a biweekly interval. This
has the advantage that changes in blood glucose can be
detected more quickly than with HbA1c and allows for
timely clinical intervention. Furthermore, the FrAm assay
is a colorimetric assay that can be readily performed in any
clinical laboratory. An improved version of the original kit
is now available from the manufacturer (Roche Diagnostic
Systems, Inc., Rahway, New Jersey). Using this improved
version, Jensen and Aaes (1992) reported a reference range
for FrAm for dogs of 259 to 344 μ mol/l (301 21.3 SD).
This result is 10-fold lower than that originally reported by
Kawamoto et al . (1992) using the older method. By extrapolation,
the reference range for cats as reported by Kaneko
et al . (1992) is 219 to 347 μ mol/l (283 32 SD). In all
cases, FrAm was shown to be significantly elevated in diabetes
indicating that they can be of clinical value to monitor
glucose control in treated diabetics. On occasion, especially
in cats, hyperglycemia or glucosuria is seen on initial
presentation and without other indications of diabetes. A
FrAm sample taken at this time can be used to differentiate
a transient from a persistent hyperglycemia.
5 . Glucose Tolerance and the Insulin Response
The glucose tolerance test (GTT) is the most important
test of carbohydrate function and is of particular value in
those cases of diabetes in which the fasting blood glucose
is only moderately elevated and the diagnosis is equivocal
(Section VIII.C). The diabetic oral GGT curve is high
and relatively flat, indicating a decreased tolerance for
glucose ( Fig. 3-12 ). The nature of the diabetic curve can
be quantitated by using the intravenous GTT. The diabetic
curve is characterized by a long T 1/2 or low k-value, which
reflects the inability of the animal to use the test dose
of glucose. The insulin response curve in type I (absolute
insulin deficiency) diabetes clearly demonstrates the
inability of the pancreas to release insulin in response to
the glucose load. It is in the absence of an insulin response,
which is responsible for the failure of the diabetic to utilize
the added glucose, that the prolonged hyperglycemia
occurs. An important factor adding to the hyperglycemia
is the overproduction of glucose by the liver. The test dose
of glucose is in effect added to the already existing oversupply
of glucose. Because the steady-state level at which
the liver ceases to supply or remove glucose is elevated in
diabetes, the liver continues to oversupply glucose, which
contributes to the slow return of the tolerance curve to its
original level.
In types II and III diabetes (see the following discussion),
there is also glucose intolerance, but this occurs in
the presence of a normal to elevated insulin. This would
mean that the insulin in the plasma of these types is unusable
or ineffective (i.e., relative deficiency) because of a
number of factors including insufficient receptors, receptor
blockage, abnormal receptor structure, or antibody
binding, all of which lead to the glucose intolerance and
the phenomenon of insulin resistance. Therefore, glucose
intolerance is seen in all types of diabetes whether there is
an absolute (type I) or relative (types II, III) deficiency of
insulin. The insulin response must be evaluated in order to
establish the type of diabetes.
6 . Insulin and the Insulin Response
Serum insulin is characteristically very low or absent in
type I diabetes, whereas it is normal to very high in type
II or III. Type I diabetes can be readily differentiated from
the other types by an absent or low fasting insulin level.
On the other hand, about 40% of diabetics have normal
to very high insulins. The classification of these diabetic
types is based on the nature of the insulin response curve
in the IVGTT. Type II has a normal to high insulin with
no increment of insulin response to the glucose load. Type
III also has a normal to high insulin; the insulin response
is inadequate and there is a delayed return to preinjection
levels ( Kaneko et al ., 1977 ). Types II and III have been
further subdivided on the basis of obesity or nonobesity
( Mattheeuws et al ., 1984 ), and their insulin levels are given
in Table 3-9 .
The classification of diabetes into types has important
therapeutic and prognostic implications. Thus far, insulin
replacement therapy is the only effective treatment for the
type I and the type II nonobese diabetic, even though islet
TABLE 3-9 Insulin Concentrations in the Various
Types of Canine Diabetes
Normal 5–20
Type 0–5
Type II nonobese 5–20
Type II obese 20–130
Type III nonobese 5–20
Type III obese 8–60
Serum Insulin
( μ U/ml)