Caninsulin-Diabetes in Dogs and Cats


  Click here for the official website of Caninsulin

First is a brochure given to vet's patients.
Second is a brochure provided to the vet .
It is provided by intervet.
Monica French from intervet gave me permission to use
these brochures on Queenie's site.
Thank you Monica !!!

This first brochure is provided to owners of diabetic pets!
Diabetes in dogs and cats!
Maybe you were shocked to learn that your pet was diagnosed
as suffering from diabetes, but fortunately diabetes in pets can
be treated very successfully, although it requires a good deal of
attention and day to day consistency.
What is diabetes?
During digestion in the intestines, food is reduced to components that can
be used by the body:  carbohydrates are converted into sugars, glucose
being the most important one.  Glucose is resorbed from the intestines into
the blood to provide the body cells with energy.  Cells can only absorb
glucose when insulin induces them to do so.  When an insulin shortage
exists, too much glucose remains in the blood and this condition is callled
diabetes.  Diabetes is therefore really an insulin shortage.
Insulin
Insulin is produced by certain cells (islet cells) situated in the pancreas.
Some of these cells cannot produce sufficient insulin and sometimes none
at all.  This condition is usually found in older bitches and castrated male
cats, but diabetes can be seen in young dogs as well.  In some breeds the
number of cases exceeds the average.
What are the symptoms?
When blood contains a high concentration of glucose, the kidneys will
start to excrete this into the urine, (the kidney threshold is exceeded).
This takes an extra amount of fluid, and therefore the patient will drink
and urinate more.  Because glucose is an important fuel (energy source)
and is being lost, the affected animal will eat more but still lose weight.
The condition of the coat will fall back and the animal is generally off colour.
Diagnosis
The symptoms observed will indicate diabetes, but they also be seen
in other diseases.  A definite diagnosis is made by demonstrating too high
glucose levels in blood and urine.  The determination of blood levels is more
reliable than the determination of levels in urine.
Treatment
Administration of Insulin
Diabetes is caused by an insulin shortage.  Therefore, this shortage should
be replenished daily, at a fixed time (regularly) by injecting insulin.  This may
seem dreary to you, but once you are used to doing it you'll find it's not so
difficult after all.
Because the extent of the insulin shortage is unknown, a proper dosage needs to
be assessed.  The daily dose needs to be balanced to the insulin need of your pet.
The institution of Caninsulin therapy
Your vet will establish the amount needed, based on the weight of your pet.
He will show you how to draw insulin from the vial and how to administer the injection.
Once you can do this correctly (and is really a lot easier then it seems) your vet
will provide everything you need to care for your pet at home.  At first, you will have
to check the urine 3 times a day for the presence of glucose: before breakfast, at noon
before lunch and a bit later in the evening.  This test is simply done by dipping a colour
changing strip in the urine.  During this period it may also be necessary to have the vet
examine blood samples taken 1 hour before the second meal.  Once the insulin therapy
has been stabilized, your pet will rapidly recover.
The animal will become livelier and its coat condition will improve.  The frequency of
drinking and urinating will also decrease.  The urine may now be tested less frequently.
Regular examinations remain necessary because the need for insulin can change.
Adjustment of the daily dose may then be necessary.  Once your pet is on an adequate
maintenance dose, it can lead a completely normal life.
Food and Exercise
Because the daily dose is adjusted to the amount of energy (glucose) your pet needs
every day, regularity in feeding and exercise is important.  That is why your pet
always needs to be fed always at the same time with the same amount of the same diet.
Also the amount of exercise needs to be the same.  When your pet suddenly uses a lot
more energy (a long walk, excitement about visitors) it will burn more glucose.
Sometimes this leads to a blood sugar level which is too low, and too little energy is
available for the brain.  The animal may even lose consciousness.  If that happens you
must immediately administer glucose by mouth.
Sterilization
If diabetes is diagnosed in a bitch, she will have to be sterilized as soon as possible.
One of the female hormones, progesterone, has a negative effect on sugar metabolism.
In cases where diabetes has been present for only a short time, removal of the ovaries
may lead to complete recovery.  A regular blood sugar test is necessary because the
need for insulin may rapidly decrease after sterilization.  Because progesterone-like drugs
are used to stop a bitch coming into season, this treatment needs to be stopped as well.
Expectations
After being stabilized on insulin, most patients are able to lead a normal life.  The most
important complication is a too low blood sugar level.  Although this is a rare complication,
it is important for you to know how to deal with such cases.
Hypoglycemia
Too-low blood sugar levels
When the blood sugar level is too low, the brain will not receive enough energy (glucose).
This could lead to a potentially fatal situation and it is therefore important to be able to
recognize the symptoms.  The following symptoms may be seen:
unrest, trembling or shivering, strange movements, strange behaviour,
muscle twitching and even unconsciousness (coma).

        What to do:
            1.  Give food immediately.
            2.  If the animal refuses to eat, administer a glucose solution as quickly as possible.
                1 gram per kilogram body weight.  This solution should be poured carefully into
                the cheek pouch.  If the animal is unable to swallow, rub the glucose powder onto
                the gums (especially under the tongue).
                As soon as recovery is seen: give food.
                Keep an eye on the patient in case signs return.
                Note:  It is wise to always keep an amount of glucose ready for use.
            3.  If the condition of the animal becomes worse, (muscle-twitching, unconsciousness)
          call your vet immediately.

            What you will need for the treatment of diabetes:
            1.  Caninsulin (insulin for dogs and cats)
            2.  Insulin syringes 40 internation units (I.U.) per ml
            3.  Test strips for testing urine for glucose
            4.  Glucose or glucose water
            5.  Complete commercial food

        To be filled out by your veterinarian
            Name of pet______________________
            Age_____________________________
            Breed____________________________
            Sex______________________________
            Weight___________________________

        Daily Schedule
            Insulin
       To be given immediately after the morning meal.
            Insulin should be kept in a refrigerator but not in a freezer.
            Before use, the bottle must be agitated but not shaken.
            The insulin subcutaneously (under the skin) should be injected using special syringes.

            Starting dose will be determined by your vet.

        Food
       The following is essential:
            Give daily, enough food to maintain, gain or loss of weight according to each patient's needs.
            Your veternarian will calculate the needs of your animal and will indicate to you the type and
            amount of food to be administered.  Give half the ration in the morning, the other half in the
            afternoon. (Cats can be particular about their food: any accepted menu will do in principle).
        Caution
       *The compostion of the insulin solution is such that a 7.5 hours interval must be observed
            between the injection and the second meal.
            *NOT EATING: NO INSULIN
            When your pet has a reduced appetite and eats only half of its meal, then also give half
            the daily dose of insulin.  If this situation lasts for more than 2 days (through illness for
            example), consult your vet.
            *Give no extra food, biscuits or other "goodies" in between meals.

            Your vet will tell you the amount and kind of food to feed in the morning and afternoon.

            Urine test for glucose
            Test urine in the morning (before morning meal).
            Test urine in the afternoon (before afternoon meal).
            Test urine in the evening.

            Blood sugar test
            In the afternoon, before the afternoon meal, (by vet is necessary)

            Glucose
            Have the correct amount of glucose(or corn syrup) handy in case symptoms
            of too low blood sugar level are seen (hypoglycemia)
            Ask your vet the quantity of glucose solution or corn syrup that your pet will need.

            Treatment monitoring
            To easily monitor the insulin treatment, it is advisable to fill out the following table daily.
            (Take it with you when consulting your vet)
 

Date Dose 
Caninsulin 
in I.U.
Urine Test Urine Test Urine Test Blood Test Appetite Appetite Notes
    8:30 am 15:30 pm 21:30 pm 15:30 pm 8:30 am 16:00 pm  
                 
                 
                 
                 

Brochure provided to Veternarians from Intervet
on Caninsulin and Diabetes Mellitus!

INTRODUCTION
Diabetes mellitus is a fairly common endocrinopathy in small animals.
This disorder, which is the result of a relative or absolute insulin
deficiency, is characterized mainly by high blood glucose levels so that
the renal threshold will be exceeded.
As a result, glucose is excreted in the urine.
This osmotic action of glucose leads to polyuria and, through loss of
fluid, to polydipsia.
In addition, metabolism is impaired so that the general condition of the
animal  deteriorates which finally leads to death.  The factors which play
a role in this process will be discussed in the chapter
"Symptoms of Diabetes Mellitus".
The prognosis of diabetes mellitus depends mainly on the cause, an early
diagnosis and on an adequate therapy.  Most forms of diabetes can
successfully be treated with insulin.  Besides insulin administration,
dietary adjustments and a regular life-style (daily exercise schedule) play
important roles in the total treatment regime.  Optimal communication and
cooperation between veterinarian and owner is particularly important in the
early stages of treatment.  The attitude of the veterinarian largely
determines the owner's motivation and acceptance of the treatment.

INCIDENCE
Estimates of the occurence of diabetes mellitus range from 1:66 to 1:2000
in dogs and 1:800 in cats.
The disease mostly occurs in adult and elderly dogs and cats and
particularly in bitches and neutered male cats.  A breed disposition in
dogs has been reported with respect to several types of diabetes mellitus.
-in toy poodles, terriers, Cocker Spaniels, and Dachshunds, the disorder
generally occurs at a later age;
-large breeds such as Doberman Pinscher, Alsatian, Labrador and Golden
Retriever have a tendency to develop juvenile diabetes mellitus;
-inherited diabetes mellitus is suspected in several lines of Pomeranian
dogs and Golden Retrievers.

AETIOLOGY
The basic abnormality occuring in diabetes mellitus is a decreased
peripheral use of glucose. There are several types of diabetes mellitus:
1. Type I diabetes
Characteristics:
-insulin plasma level too low;
-impaired insulin response after glucose administration(glucose tolerance
test);
-good response to insulin treatment.

Potential diabetes mellitus is sometimes regarded as precursor type I
diabetes.  It involves impaired B cell function which results in a slightly
increased blood glucose level, but one which remains below the renal
threshold
(10 mmol/l).  This disorder is typically characterized by polyuria and
polydipsia, but without signs of glucosuria.

Type I diabetes is the most common mainfestation of diabetes mellitus.
It occurs if the demand for insulin exceeds the ability of the B cells of
the Islets of Langerhans to produce insulin.  This situation can be caused
by the following primary conditions:
Oestrus, pregnancy, obesity, stress and various disorders which stimulate
the release of hormones and other biochemical compounds which counteract
the interaction of insulin with the target cells.  As a result, the demand
for insulin will increase, eventually exhausting the B cells.
As long as the B cells remain intact, the condition will be reversible and
the patient will recover after the primary cause has been eliminated.
Diabetes mellitus becomes irreversible when the B cells degenerate due to
exhaustion over a long period.

PROGESTERONE
In view of the above, special consideration of the influence of
progesterone seems appropriate.  Prolonged exposure to progesterone is one
of the most common causes of diabetes mellitus.  For this reason elderly
bitches form a relatively large patient group.
Progesterone stimulates the release of growth hormone, resulting in a
relative deficiency of insulin through counteraction of the insulin
effect.
In the early stage, diabetes mellitus is reversible but later the disorder
becomes permanent.
This mechanism can either be caused by constant exposure to endogenous
progesterone in elderly bitches left to cycle normally or by repeated
treatment with various progesterone derivatives used for oestrus control.
Type I diabetes mellitus in cats can also be induced by prolonged exposure
to progestogens used either for permanent or temporary oestrus suppression
or for treatment of skin conditions such as miliary dermatitis.

GLUCOCORTICOSTEROIDS
Another well-known primary cause of type I diabetes, in both male and
female animals, is an excess of circulating glucocorticosteroids.
Glucocorticosteroids act antagonistically to insulin by, for example,
stimulating gluconeogenesis.  This will result in hyperglycemia and if the
insulin release remains insufficient, diabetes mellitus.  Here also the
induced diabetes will initially be reversible.

50% of dogs with hyperadrenocorticism (Cushings's syndrome) are
hyperglucemic during periods of fasting.  In 10% of such patients this
condition will develop in to  a clincial diabetes mellitus.
Therapeutic use of glucocorticosteroids only incidentally
induces diabetes mellitus.
It must be borne in mind that the effects of progestogesn and
glucocorticosteroids are additive.  The risk is increased if a patient is
exposed to both hormones.

OTHER CAUSES
Disorders of the pancreas can play a major role
in the aetiology of type I diabetes.
Examples of such disorders include: infections, auto-immmune diseases,
surgical trauma, tumours, ameloid dispositon and congenital dysfunction.
Degeneration of the Islets of Langerhans due to ameloid dispostion has been
found in many diabetic cats.

JUVENILE DIABETES
Juvenile diabetes is caused by a congential dysfunction of the pancreatic B
cells.  This condition leads to an absolute deficiency of insulin which
results in hyperglycemia and diabetes mellitus.
This form of type I diabetes has been sporadically diagnosed, although its
aetiology is still unknown.
Juvenile diabetes is clincally seen in young dogs of certain breeds(see
incidence) under one year of age.

2. Type II diabetes
Characteristics:
-normal or increased insulin plasma level
-no insulin response after glucose administration
-poor response to insulin treatment.

A relative shortage of insulin, due to the action of certain insulin
antagonists or as the result of insulin insensibility of peripheral tissue
(particularly fatty tissue), occurs (insulin does circulate, but cannot
act) whereby the blood glucose level becomes too high.

This type of diabetes is very rare in dogs and cats.  It is extremely
difficult to regulate patients suffering from this type of diabetes.

SYMPTOMS OF DIABETES MELLITUS
Insulin deficiency impairs the uptake of glucose by cells.  The organism
has to deal with a complex situation, e.g. extracellular hyperglycemia and
intracellular glucose deficiency at the same time.  The consequences of
this are reflected in the following scheme:

Energy shortage intracellular



conversion of fatty tissue------>increase in fatty acids in plasma---->
ketosis-------->keto-acidosis ketonuria-------> acidotic coma


Energy shortage intracellular
increase in gluconeogenesis---------->increase in urea
roduction---->uraemia


Energy shortage intracellular
increase in gluconeogenesis---->decrease in protein
synthesis-cachexia/lethargy-polyphagia-increased susceptibilty to  bladder
infections--impaired wound healing--poor coat condition


Hyperglycemia extra-cellular
hyperosmotic plasma--->dehydration of cells--->hyperglycemic coma

exceed of the renal threshold--->glucosuria--->high specific gravity

exceed of the renal threshold-->glucosuria-->polyuria

osmotic diuresis-->polydipsia--->hypodelaemia hyponatriaemia

Polyuria, polydipsia and polyphagy in combination
with loss of body weight, poor coat condition and letargy 
are the most common, directly observable clinical symptoms.
A diagnosis of diabetes mellitus must be confirmed 
by blood and urine tests.

Normal values for the blood glucose level 
in the dog range from 3.9 to 5.0 mmol/l (70.27 to 90.1) 
and in the cat from 3.4 to 5.7 mmol/l(61.26 to102.7) (fasting). 
In cases of potential diabetes mellitus, the value is 5 - 7mmol/l. (90 to 126).
The renal threshold is 10 mmol/l.(180.2 for conversion)
Blood glucose levels which exceed this threshold result
in excretion of glucose in the urine(glucosuria).
In cases of clinical diabetes mellitus, blood glucose 
levels of 10 mmol/l(180) and higher are found.

Temporary hyperglycemia can occur in cats under stress(for example in cases
of urethra obstruction, but also during blood sampling).  Glucosuria will
be seen if the renal threshold is exceeded.
Since diabetes mellitus is not implicated in these cases(also indicated by
the history), treatment with insulin in contraindicated.

The terminal phase of diabetes mellitus is often characterized by
keto-acidosis or hyperosmolaric non-ketotic coma(see scheme).

Symptoms of polyuria and polydipsia are often reported by the owner to
persist for a long period.
Generally, keto-acidosis develops more rapidly.  Symptoms such as severe
depression, anorexia, vomiting, oliguria or anuria and hyperventilation can
be observed.  Sometimes even a stong acetone odour to the patient's breath
is noticeable.
A patient in hyperosmolaric, non-ketotic coma has usually been ill for a
longer period.  The animal is very lethargic but non-keototic.  Due to
hyperosmolaric dehydration, the cells of the CNS are impaired.

TREATMENT OF DIABETES MELLITUS
As mentioned previously, the treatment of diabetes mellitus can only be
successful if several aspects are taken into account.
Not only the veterinary surgeon, but also the owner plays a major role.  It
is advisable to invest time in giving the owner complete information on all
aspects of the treatment, including the importance of dietary regulation
and a regular exercise schedule.
Ovario-hysterectomy

If diabetes mellitus has been diagnosed in an entire bitch, immediate
spaying should be considered.  The chance of complete recovery, without the
need for life-long insulin treatment, increases as the period of clinical
symptoms becomes shorter.  In animals in a condition permitting surgery,
ovario-hysterectomy has to be performed under stringent
monitoring(intravenous fluid therapy).  If the condition of the patient is
critical(dehydration, anorexia, uraemia, severe hyperglycemia and
glucosuria) to the extent that surgery is contraindicated, the primary
steps to be taken include fluid and insulin therapy.
In case insulin therapy has been implemented,  the insulin dose has to be
reduced to 30% on the day of the operation(because of the pre-operative
fasting).  It is even better to cease insulin administration and to give
intravenous therapy to provide sufficient extra fluid.

After surgery, a regular check on blood glucose level is necessary.  The
insulin requirement may decrease rapidly after the source of progestogen
has been removed.  Extra control needs to be continued until a stable
situation has been regained.

In cases of completely reversible diabetes mellitus resulting from the
influence of endogenous progesterone, several weeks are sometimes needed
for full recovery of the B cells.

Although the b cells occasionally cannot regenerate completely, the insulin
response of the tissue cells will often improve somewhat after
ovario-hysterectomy.  While maintaining a check on blood glucose levels,
the use of a lower dose of insulin might be appropriate.

Diet
Composition and quantity of meals must be similar from day to day.  Since
this is difficult to establish when feeding left-overs, etc.   It is better
to feed commercial pet food, unless this is not accepted by the patient.
note:Queenie has been on a homemade diet and has been a
diabetic since April 23rd, 1995

Cats often are very fussy in their choice of food.
In principle every type of food that the cat will accept will suffice(in
many cases canned prescription diets are well accepted.)

The amount of food should fulfill requirements of the animal depending on
whether the weight has to be maintained, decreased or increased.

The treatment schedule is based on the biphasis activity of the most
suitable insulin preparation, a mixture of amorphous and crystalline
insulin.
See figure 1 ( this is not included . It is a graph showing when caninsulin
peaks the 30% and 70% parts)
The total daily amount of food must be divided into two meals, synchronized
with the maximum activity of insulin.
For example, the first meal to be given at 08:30 hours and the second meal
7 1/2 hours thereafter, at 16:00 hours.
As a result, an acceptable constant blood glucose level during the greater
part of a 24 hour period will be established.
If insulin is overdosed, hypoglycemia will occur at times of the day during
which the animal can be observed, provided that insulin has been
administered in the morning.

It is safer, for both dogs and cats, to first observe the animal's appetite
before giving the insulin injection.
Administration of insulin can then be done during 
or directly following the meal.
If the patient eats half the meal only, giving 50% of the dose in
indicated.  If the animal has been vomiting the previous day, it is
advisable to wait one half hour after feeding before injecting the insulin,
so that retention of the food can be assured.

In the first phase of insulin regulation, the patient is sometimes
reluctant to eat due to hyperglycemia.  In such cases, insulin must be
administered and the food must be removed after one hour.
If cats continue to refuse to eat in the morning, the best method is to
leave the food available so that the animal  can eat when appetite is
stimulated due to declining glucose levels after insulin administration.
If the patient is not willing to, or cannot eat(fasting, vomiting, diarrhea
or illness) after regulation has been achieved, insulin administration is
contraindicated.  This situation of fasting and retention of insulin can
safely be permitted to remain for 3 or 4 days, as long as the body-fluid
balance is ascertained.
However, hyperglycemia with polyuria and polydipsia may occur.  During the
recovery phase, uptake of food and insulin dose have to be increased
mutually (1/4 portion food-1/4 insulin dose, etc.).

Insulin Treatment
1. Insulin Preparations
Up to now, a variety of preparations developed for the human field have
been used in veterinary practice.  Nowadays, novel human insulins are
produced by synthetic or biotechnological methods.  This method of
production is very expensive and has been developed in order to avoid the
presence of foreign proteins in the final product.
As the result of these measurements, the risk of immunological side effects
in human beings can virtually be excluded.
These expensive preparations do not appear to be necessary for veterinary
use, although products containing bovine insulin may sometimes induce a
slight insulin resistance.  This is due to the fact that bovine insulin
differs in its amino acid structure from canine insulin at two sites.  The
consequence of this is that the dosage needs to be slightly increased in
cases if insulin resistance.  Furthermore, if the insulin therapy is
converted from bovine insulin to purified porcine insulin, one must be
aware of the fact that a decrease in dosage might be necessary.  Porcine
and canine insulin have an identical amino acid structure.  For this
reason, highly purified insulin derived from porcine pancreas is most
suitable.
Various solutions and suspensions are available, each one with a specific
duration of activity.  Since one injection per day is desirable, the use of
a preparation having a duration of 24 hours is preferred.  An insulin-zinc
suspension is very suitable for this purpose.

Caninsulin is an aqueous suspension of 40 I.U. highly purified porcine
insulin per ml, consisting of 30% amorphous and 70% crystalline zinc
insulin.  The amorphous fraction will reach its maximum effect
approximately 3 hours following subcutaneous administration and the total
useful effects lasts for about 8 hours.  Thereafter, the effect is taken
over by the crystalline fraction, having a slower onset with a maximum
effect ranging from 7 to 12 hours following injection.  Afterwards, the
effect gradually declines to zero at 24 hours after administration(see
Figure 1)(not Included in the email).
various other types of insulin preparations are available, but can only be
used in exceptional situations.  These types are less suitable for routine
treatment of diabetes mellitus in dogs and cats

-Aqueous insulins can be used in critical cases of diabetic keto-acidosis.
After intravenous administration, the plasma half-life ranges from 5 to 15
minutes.  The onset after sucutaneous injection is 30 minutes with a
maximum effect after 2 hours.

-Compared to Caninsulin, the onset of a mixture of 25% aqueous and 75%
crystalline insulin is somewhat earlier, but the total useful effect is
only 18 hours.

-100%Amorphous zinc insulins have an onset of 2 hours, and a total useful
effect of 12 hours only.

-100% Crystalline zinc insulins have a delayed onset and a total effect of
26 hours(overdosing results in a long period of hypoglycemia!).

2. Starting Dosage
Caninsulin contains 40 I.U. per ml and should be injected by the
subcutaneous route.  Intramuscular administration is also possible,
although resorption, onset and duration of action are different.  In
addition, intramuscular application might cause discomfort to the patient.
Therefore, the intramuscular route is not generally recommended.  In order
to obtain a homogenous suspension, shake the vial gently before use.  The
use of U40 insulin-syringes is advisable to ensure accurate dosage.

In July of 2008 vetsulin changed their recommended starting doses.
I cannot find on caninsulin website if they followed suit but I am going to assume they did.
New vetsulin recommended dosing can be found on the beginner's page.
 http://www.caninediabetes.org/beginners.html 
Vetsulin has cut their recommended doses by HALF to avoid hypoglycemia.

The following are the old recommended doses for vetsulin, click on the above link for new dosing recommendations.
I left the old chart(below) up to show the drastic change in recommended doses
Dog
The starting dosage for dogs is 1 I.U. per kg body weight, plus a
supplementary dose related to body weight.

Body weight  Dose supplement
<10 kg   1 I.U.
approx. 10 kg  2 I.U.
12-20 kg  3 I.U.
>20 kg  4 I.U.

Examples

Body weight dose  Starting Dose Dose Supplement  Total
7 kg 7 I.U. 1 I.U. 8 I.U.
10 kg 10 I.U. 2 I.U. 12 I.U.
15 kg 15 I.U. 3 I.U. 18 I.U.
35 kg 35 I.U. 4 I.U. 39 I.U.

Cat
The starting dose for cats is 2-4 I.U. depending on body weight.
Although it has been found that the majority of cats
eventually need 1 I.U.per kg body weight,
it is not without risk to start directly with such a
dosage, particularly in obese cats.  It is preferable to increase the dose
by steps of 0.5 I.U., guided by the plasma glucose level.
 

3. Control and Continuous Regulation
Therapy has to be monitored by means of urine glucose assessments and since
this is often not sufficient on its own, by plasma glucose assessments.

The urine can by checked by the owner through the use of test strips.  In
the initial stage of therapy it is advisable to test three times per day.
After regulation has been achieved, routine tests before the morning-meal
two to three times weekly will suffice.
The best times for carrying out urine glucose tests are
 

1. Directly before the morning-meal  _08:00 hrs.
2. Around the time of the 2nd meal   _15:00-16:00 hrs
3. In the evening when the insulin action declines     _21:00-22:00 hrs

From the results of urine glucose assessments, the insulin dose can be
adjusted.(for explanation, see 4: Results and complications during
regulation)
Here is the chart
 

Results 
Time 1
Urine Glucose
Time 2
Assessment
Time 3
Adjustment of Dose
trace -negative -negative none:correct dose
trace -negative +positve none:correct dose
+positive -negative -negative none:correct dose
+positive +positive +positive +10%:dose too low
-negative -negative -negative -10%:dose too high
+positive -negative +positive -20%: Somogyi effect
During the regulation phase, blood glucose assessment must be performed in
addition to the urine test.  This is particularly needed when the results
of the urine test are near the detection level and the correct insulin dose
has almost been reached.  A positive urine result indicates only that there
has been a moment of exceeding the renal threshold since the last time of
urinating.
In addition, it is sometimes impossible for the owner to sample urine three
times daily.
By means of blood testing, the reaction of the blood glucose level to
administration of insulin and dosage enhancement can be assessed.  If the
glucose level remains below the renal threshold, the owner is not able to
observe possible fluctuations.  For instance, the glucose level can either
be still sufficiently high or far below the renal threshold,
near severe hypoglycemia.
The preferred time for blood testing is 15:30 hrs, shortly before the
second meal.  At this time it can be determined if the blood glucose level
has declined excessively due to insulin given the same morning.
From these blood glucose assessments, the insulin dose can be adjusted
(for explanation, see 4:Results and Complications):
 
Result plasma glucose assessment
(initial value for ex. 20 mmol/l)
Adjustment of dose
5-9 mmol/l none, correct dose
10-12 mmol/l after the first day none, repeat dose
10 mmol/l after sluggish decline +10%, dose too low
5 mmol/l  -10%, dose too high
     4. Results and Complications during Regulation
If a correct dose of insulin has been administered, the morning blood
glucose level(before injection) is just above the renal threshold(trace of
glucose in the morning urine).  After insulin injection, the level declines
to the desired value of 6-8 mmol/l, but not lower due to feeding.  During
the night, due to a decreasing effect of insulin, the blood glucose
increases to a level slightly above the renal threshold.  In case the
glucose level declines rapidly after initializing the therapy, and still is
(slightly) above the renal threshold at 15:30 hrs, a similar dose has to be
given the next morning.  Here increase in the dose by 10% can be hazardous.

The glucose level remains above the renal threshold of 10 mmol/l for 24
hours in case of a too low insulin dose.  As a consequence, the patient
constantly suffers from glucosuria, polydipsia and polyuria.  The dose must
be increased by steps of 10%(cats 0.5 I.U.).  If no effect can be observed,
steps of 20% have to be considered.  It is extremely ill advised to
regulate the patient based on convenience so that the glucose level always
will remain just above the renal threshold(no risk of over-dosage, only
urine tests necessary).  Such a method can have severe consequences for the
eyes(cataracts) and kidneys (degeneration and infections).

In situations where the dose is far too high, hypoglycemia will occur.
This is a serious situation which may occur at any stage in diabetes
mellitus, even after stable regulation has been achieved (for example due
to loss of appetite, vomiting, excessive exercise or unknown causes).
Symptoms are, in order of ascending severity, hunger, restlessness,
shivering, ataxia, disorientation, convulsions and coma.  Immediate oral
application of a glucose solution(1 gram per kg body weight) or corn syrup
by the owner can alleviate this condition.  The owner must be fully aware
of the necessity of having glucose or corn syrup always available.
Following this emergency measure, food must be provided(related to the
short duration of effect, 30-60 minutes, of the glucose solution).  Food
must be given repeatedly with intervals of 1-2 hours until the effects of
the insulin has been eliminated.

In case the insulin dose is slightly too high, the Somogyi-effect may
occur.  This is a chain reaction of the body to a sluggish decline of the
blood glucose leve.  If after insulin injection the glucose level has
decreased to approx. 3 mmol/l, the patient will become hungry and restless
or lethargic.  Due to a decling glucose level in the CNS, adrenaline and
subsequently cortisol, glucagon and growth hormone will be released.  These
hormones will induce an increase of the blood glucose level(through
gluconeogenesis, release of glucose from hepatic glycogen and increase in
the peripheral resistance to insulin).  This results in a rapid rise of the
glucose level shortly after the second meal.  During the rest of the 24
hour period, the blood glucose level further increases to 15-18 mmol/l or
even higher.  The urine glucose level is negative during the day, but rises
in the evening and night and will become strongly positive in the morning.
Symptoms of polyuria and polydipsia will occur.  This condition bears the
risk that if guided only by the results of urine tests, the insulin dose
will be increased.  This is absolutely contraindicated since in this way a
severe hypoglycemia will be induced.  In contrast, the insulin dose must be
decreased by 20%!

Alternatives
In the human field, medicines are available for treatment of various types
of diabetes mellitus (for example tolbutamide).  These compounds stimulate
the release of extra insulin by B cells in the pancreatic Islets of
Langerhans.  Since the aetiology of most types of diabetes mellitus in dogs
and cats is related to excessive stimulation and thus exhaustion of the B
cells(type I diabetes) it should be clear that these types of preparations
are strictly contraindicated for veterinary use.
Hence, veterinary alternatives for insulin are not available.

Prognosis of Diabetes Mellitus
As stated earlier, the prognosis for a diabetic patient depends completely
on the level and knowledge and dedication of the owner.  These are closely
related to the attitude and to the degree of explanation given by the
veterinary surgeon.
It must be said that treating diabetic patients is interesting, rewarding
and certainly not a complicated as is sometimes thought.
The majority of diabetic patients can be brought to a stable condition
within one week after intitial regulation.

Dogs
The survival time of regulate dogs depends on age and ranges on average
from 2 to 5 years.  An unexpected sensitivity for insulin resulting in
fatal hypoglycemia must always be taken into account.
Apart from this routine control of a regulated dog sometimes reveals a
minor hypo or hyperglycemia.  If all signs are normal(urine, appetite,
water uptake, general condition, etc.) it is advisable to check the
following day again before and adjustment of the insulin dose is
considered.

Cats
In many cases cats can be satisfactorily treated for years without
adjustments to the dose.  However, it is not unusual that, after several
months or years for instance, either sudden withdrawal of insulin or major
increase in the dose is required.  These occurrences always necessitate
concurrent monitoring of blood and urine.
It is sometimes seen that during initial regulation the blood glucose level
fluctuates in such a way that stabilization cannot be achieved throught
dose adjustments.  This situation can be dealt with by choosing a dose
resulting in optimal clincal condition of the patient.  It must be borne in
mind that influenced by stress(visit to the veterinary clinic) major
fluctuations of the blood glucose level may occur.  In such cases it is
preferable to take action only if the experience of the owner indicates the
necessity.

Final Remarks
After diagnosing diabetes mellitus, one must always try to find a primary
cause.  In cases of Cushing's syndrome or progestagen therapy specific
measurements have to be taken to remove or alleviate these primary causes.
 Very occasionally it may appear impossible to regulate a patient by using
Caninsulin and by following the indicated schedule.  For example, it might
be that the patient either suffers from another type of diabetes mellitus,
rarely found in dogs and cats, or from another metabolic disorder. It is
beyond the scope of this brochure to discuss these aspects extensively.

The vet's copy of Caninsulin was typed with permission from Intervet.
This is not to meant to take the place of advice from your vet.  This
brochure is available to your vet from intervet.

 If you are using caninsulin or vetsulin you do NOT have to use the large guage (29 guage) syringes that are produced by intervet for caninsulin and vetsulin.  Here is a conversion page for using U100 syringes manufactured for human diabetics ( cheaper and more comfortable)
because you can purchase up to 31 guage short)
 http://www.caninediabetes.org/u40conversion.html

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