Definition
Diabetes Mellitus is a group of conditions in which there is a deficiency
of the hormone insulin or an insensitivity to it. Insulin is produced in
the islet cells of the pancreas and is normally responsible for controlling
blood concentrations of the body's main fuel, glucose. In normal animals,
insulin does this by preventing glucose production by the liver and ensuring
that excess glucose derived from food which is not needed for energy is
put into body stores.
In a diabetic animal there is insufficient insulin to switch off glucose
production by the liver or to efficiently store excess glucose derived
from energy giving foods. This means that the blood concentration of glucose
rises and eventually exceeds a level beyond which the kidneys let glucose
leak into the urine. This loss of glucose in urine takes water with it
by a process called osmosis and causes larger volumes of urine to be produced
than normal. The excessive loss of water in urine is compensated for by
thirstiness and increased water consumption. The principal clinical signs
of an animal with diabetes mellitus are therefore polyuria (excessive urination)
and polydipsia (excessive water consumption). In addition, diabetic animals
tend to lose weight because they breakdown stores of fat and protein (muscle)
to make glucose and ketones (an alternative fuel) in the liver. Other clinical
signs diabetics may include: cataracts, polyphagia (increased appetite),
exercise
intolerance and recurrent infections. If the production of ketones by the
liver is excessive a condition called ketoacidosis occurs which makes the
animal very unwell.
Therapy
 Oral
hypoglycemics
Oral hypoglycemics are tablets used in the treatment of human diabetes
mellitus which can lower blood glucose in some cases. In general, they
are not useful for the treatment of diabetes mellitus in dogs but are some
use in a small proportion of diabetic cats.
Insulin
Insulin is the treatment of choice for diabetes mellitus in animals. Insulin
must be given by injection because it is a protein and would be digested
in the intestine if it was given as a tablet. Insulin is available as pharmacological
preparations for subcutaneous injection which have been formulated to slow
its absorption and prolong its action. There are three types of prolonged
duration insulin preparations: lente (mixed insulin zinc suspension), isophane
(NPH) and protamine zinc insulin (PZI). Of these, protamine zinc insulin
has the longest duration of action and lente and isophane insulins last
long enough to be used on a once, or occasionally twice, daily basis in
diabetic dogs.
There are prolonged duration insulin products available in Britain,
most of Europe, Canada and Australia with licenses for treating dogs and
cats (Caninsulin, Insuvet Lente and Insuvet PZI).
Insulin products have to be treated carefully. They must be thoroughly
mixed prior to use and must not be frozen, heated or shaken vigorously.
Stabilization
Unfortunately, there is no standard dose for insulin which can be applied
to all animals. Each diabetic animal has to have its dose tailored to its
individual needs which is done over a stabilization period. After such
a period, maintenance insulin doses should remain relatively constant.
In order to achieve stable control of a diabetic animal's blood glucose
by insulin, all the other factors which affect blood glucose concentration
must be kept constant from day to day. These factors include the composition,
volume and timing of meals and the amount of exercise the animal gets.
To keep diet constant from day to day it is best to use commercially
produced rather than home made diets. Certain prescription or veterinary
diets can be a useful adjunct to insulin therapy such as Waltham Canine
High Fiber, Hill's w/d or r/d. These diets should be avoided in underweight
diabetics which need Waltham Concentration Diet, Hill's p/d or i/d. If
special diets are unavailable then standard canned pet foods are acceptable.
There are a number of different ways to stabilize a diabetic animal.
Some dogs are managed well with once daily injections but some will require
twice daily. Some will be stabilized using blood glucose measurements taken
by the veterinarian and others might be stabilized using urine glucose
results. In some cases, hospitalization is necessary and in others it is
not.
After stabilization has started the veterinarian often finds it useful
to create a serial blood glucose curve by repeated measurements of blood
glucose regularly throughout the day. Such a curve can be used to decide
if the dog needs twice daily injections of lente or a change to PZI insulin.
The insulin treatment of cats is similar to that of dogs but requires
at least twice daily injections of lente insulin or sometimes even twice
daily injection of PZI because cats metabolize insulin much more rapidly
than dogs.
One disadvantage to relying solely on pre-injection urine or blood glucose
results is a phenomenon known as Somogyi overswing or insulin induced hyperglycemia
(high blood sugar). This is when an excessive insulin dose lowers blood
glucose too far and the body responds to this potentially life threatening
situation by producing hormones which are antagonistic to the effects of
insulin. The release of these hormones causes blood glucose to rise again,
often to very high levels which can spill over into the urine and produce
strong positive morning urine glucose results. If adequate care is not
taken, these results can be mis-interpreted by an insulin adjustment protocol
as indicating a requirement for an increase in dose. Such an increase will,
in fact, only make matters worse. The possibility of inducing Somogyi overswing
can be reduced by measuring urine glucose 3 times a day or by relying on
nadir (lowest point in the day) blood glucose results for making insulin
dose adjustments.
Problem cases
Non-specific
illness
Dogs which are off their food or need to be fasted as part of the management
of vomiting or diarrhea need to continue to receive insulin, since withholding
both food and insulin is likely to start the production of ketones and
this will make the dog more unwell. Usually half of the dog's normal requirement
will prevent ketoacidosis and will be safe.
High
insulin requirements
There are a number of conditions which can be associated with insulin insensitivity
and therefore high insulin requirement (greater than 2 IU/kg). One of these
results from insulin antagonism by progesterone in bitches which have recently
been in season or which have had treatment to prevent them having seasons.
Another is that caused by high levels of cortisol in diabetic dogs which
also have hyperadrenocorticism (Cushings disease) or which have had repeated
long acting glucocorticoid (steroid) injections. The best tests for hyperadrenocorticism
are the low dexamethasone suppression test or the ACTH stimulation test
but the results of these sometimes need to be interpreted with caution
in diabetic dogs. Insulin insensitivity also occurs in dogs with chronic
infections or chronic kidney failure.
Somogyi
overswing
See above. This can be associated with unusually high doses of insulin
and continued clinical signs of polyuria and polydipsia, particularly in
the evenings when blood glucose has been increased by the release of protective
hormones.
Rapid
insulin metabolism
In some dogs, even the prolonged duration insulins are used up very quickly
and are no longer effective after 12 or 14 hours. This means that clinical
signs will reappear in the second half of the day. This situation is best
discovered by serial glucose analyses (12 - 24 hour blood glucose curve)
and can be remedied by the use of twice daily injections or a longer acting
preparation.
Hypoglycemia
In diabetic animals treated with insulin there is some risk that hypoglycemia
may occur. It is rare for a dog or cat to die of this condition but it
is possible and owners should be appropriately warned and trained by the
veterinary team responsible for their pet's management. It is most likely
to happen if the animal is accidentally over-dosed with insulin, over-exercised
or fails to eat its morning meal. The first noticeable clinical sign is
hunger followed by lethargy and sleepiness. If untreated, stumbling and
staggering ensue followed progressively by twitching, convulsions, coma
and death. If the animal is still conscious, treatment is by offering food,
particularly glucose containing foods such as biscuits or chocolate. If
it is unable to eat, then glucose must be administered by mouth or by intravenous
injection. Dissolved glucose powder or syrup will be absorbed quickly through
the mucosa if poured into the side of the mouth. It is not necessary for
it to be swallowed. HYPOSTOP or GLUTOSE 45 are a 40% dextrose gels which
are convenient to carry and easily administered orally. There are also
20 and 40% dextrose (a form of glucose) solutions available for the veterinarian
to use in emergency treatment.
Ketoacidosis
Ketoacidotic animals are usually collapsed, dehydrated and smell of ketones
(like nail varnish remover). These dogs require more intensive therapy
than normal diabetic dogs and this should include intravenous fluid and
special soluble insulin therapy. Often the treatment of diabetic ketoacidosis
is an intensive care situation. |
