What is diabetic clinical remission and when does it occur?
Diabetic clinical remission is a complete or partial disappearance of the clinical signs of diabetes in response to insulin treatment. This is seen not infrequently in diabetic cats with remission rates of at least 25% probably depending on the time between the onset of the diabetes and the start of appropriate treatment.
Remission should not be confused with potential diabetes mellitus seen in female dogs during metoestrus, in which the pancreatic islets are still able to function but signs of diabetes appear as a result of insulin resistance caused by progesterone-induced production of growth hormone by the mammary gland. These dogs are not truly diabetic but can become so if not treated appropriately (ovariohysterectomy/ovariectomy).
Can Caninsulin be diluted?
Diluting Caninsulin is not advisable. Caninsulin is a mixture of amorphous (soluble) insulin and crystalline insulin. The crystalline part is relatively insoluble which is why the insulin activity lasts more than a few hours. Caninsulin has a balance between the amorphous and crystalline parts. If Caninsulin is diluted, the balance between amorphous and crystalline parts is no longer 30% and 70%, relatively speaking. The amount of soluble insulin is increased by the aqueous diluent used. This results in a larger aqueous fraction and smaller crystalline fraction.
In addition the stability of the suspension is unknown if Caninsulin is diluted. Caninsulin suspension is optimized to maintain the crystalline portion as a salt. If the water content is increased as with dilution, the solution "looks for a new balance" i.e. it is not stable.
Many specialists think the Caninsulin dosage that Intervet/Schering-Plough Animal Health recommends is too high and prefer to use two doses per day instead of one. What do you think?
Many specialists recommend twice daily Caninsulin in dogs at a maximum of around 0.5 units/kg per dose. It is important to remember that we are not treating the blood glucose concentration but the clinical condition and that many dogs clinically do very well with once daily lente insulin even although the blood glucose concentrations are not optimal for the whole 24 hours.The decision to use once or twice daily Caninsulin must be made on an individual case basis.
Caninsulin appears to have become ineffective. What do I do?
Most
apparent problems with insulin administration are simple.
It is important to check if:
If there are signs of poor glycaemic control but the blood glucose nadir is between 5 mmol/l (90 mg/dl) and 10-12 mmol/l (180-216 mg/dl) then there may be either:
Administration and storage problems
Remember that some dogs require insulin twice daily. In these animals an increase in dose may not produce an increase in duration of action but precipitate hypoglycaemia and responsive hyperglycaemia. Dogs in which the duration of insulin action is less than 10-14 hours should receive there insulin twice daily, e.g. starting at 0.5 unit per kg twice daily.
Some diabetic dogs and cats that are well regulated on Caninsuline require periodic increases in their insulin dose. Why does this happen? Is it due to the production of antibodies?
It is not unusual for insulin requirements to change with time. This is related to progression of the disease (e.g. alterations in tissue receptors, etc.) and may relate to how well the animal is really controlled within a 24 hour period.
In addition, any change in body weight or exercise pattern and ageing will also alter the insulin requirement. Also any intercurrent problem, e.g. nephropathy.
In general the published work on antibodies show that they are present in all animals treated with insulin whether the insulin is identical to their own or not. These are present early on in treatment and may in some cases decrease (rather than increase).
Antibody presence does not correlate with poor response to treatment in dogs or cats. Thus antibodies are present but no-one seems to know what role they play. Although it has been suggested that they may in fact prolong insulin action!
What should Caninsulin look like?
Caninsulin is a mixture of two different types of insulin. Normally, after gentle mixing (invert (upend) the bottle several times), Caninsulin will appear uniformly clear to slightly cloudy and should not have lumps or flakes floating in it. If you see clumps or flakes floating in the vial after you have resuspended the product, do not use it.
A small white ring of sediment may be seen in the neck of some vials of Caninsulin. The ring of sediment forms when the product has not been kept stored continuously in an upright position. A small ring of dried out insulin does not affect the quality of the product. Caninsulin should be stored refrigerated and in an upright position.
Always check on the appearance of the Caninsulin before using it!
What is the best way to go about converting a stable diabetic pet from another insulin preparation to Caninsulin?
When an insulin change is necessary, one must be very cautious. Due to the nature of the disease it is difficult to give general guidelines, although some recommendations can be made:
If ideal regulation has not been achieved - it is suggested to start Caninsulin treatment at 75-100% of the dose used for the previous insulin.
In both cases, the dose must then be adjusted until regulation is adequate again.
Dogs – an increase in insulin dose will vary according to the size of the dog.
For example, a small dog receiving 2 IU will have its dose increased by increments
of 1 IU per injection. For a larger dog receiving a starting dose of 25 IU,
increments of 3-5 IU per injection can be used.
For more information see dose adjustment in dogs.
Cats – increments of 1 IU per injection are recommended.
For more information see dose adjustment in cats.
Important:
In all cases, one should allow the animal to adapt to the new dose for at least three to four days before increasing again. Larger or more frequent increases in dose are not recommended due to individual variation in insulin responsiveness.
Monitoring after conversion
In all cases where the insulin dosage (type, dose or administration frequency) has been changed, close monitoring of the animal is necessary. Four to five days after changing to Caninsulin, evaluation of a blood glucose curve should be done to verify whether or not the dose rate, etc. are adequate.
Regulation is not always easy. The human factor can be a major source of problems. A new product at a different concentration, new syringe, and/or new treatment schedule can be confusing, especially for the pet owner. Follow-up visits are highly recommended. For more information see Monitoring.
There are needleless injectors or insulin pens available for administering insulin in humans. Can these devices be used to administer Caninsulin to diabetic dogs or cats?
Caninsulin is currently only approved for administration via syringes. For the following reasons it is not advisable to use insulin pens intended for human use:
After the first dose of Caninsulin has been withdrawn, how long can the vial be kept in the refrigerator?
Until recently (mid-2005), the Caninsulin label stated that the product should only be used for 20 days after first opening. It is usually advised that any pharmaceutical product should be disposed of around one month after opening. New studies that were carried out looked at Caninsulin use for up to 42 days after first opening. Most of the governmental authorities that regulate medicines do not allow product labels that permit product use for more than 28 days after first opening. The Caninsulin label now states, in most countries, that the product can be used for up to 28 days after first opening.
Is hind limb paresis a typical symptom of diabetes mellitus in cats?
Hind limb paresis may be the result of feline diabetes.
Hind limb paresis is also seen in a number of other conditions in cats:
I have an elderly client with a diabetic cat. Can I pre-load insulin doses into syringes to make treatment easier?
There may be a problem with re-suspending the insulin in such small doses. The best thing to do would be to try a couple of days dosing with pre-loaded syringes and see how the cat does. Depending on the response to treatment, you can then decide if pre-loading syringes for your client is viable.
Is there information about the use of Caninsulin in rabbits?
In
some countries Caninsulin is not registered for use in rabbits. It may be allowed
for use in rabbits that are not meant for human consumption. For details contact
your local Intervet/Schering-Plough Animal Health representative.
The following information is provided by Dr. Thomas Göbel (Kleintierpraxis,
Mecklenburgische Straße 27 14197 Berlin.)
Background Information
Diabetes mellitus in rabbits resembles insulin-independent diabetes in humans. Whether insulin secretion is limited, maintained or elevated, tissue sensitivity to insulin is decreased (peripheral insulin resistance), resulting in a relative insulin deficit. The characteristic clinical signs are polydipsia, polyuria as well as polyphagia and weight loss. Occasionally, uni- or bilateral cataracts are observed. There is also glucosuria.
The diagnosis is made based on the history, clinical signs and blood sugar concentrations measuring repeatedly above 300 mg/dl (16.7 mmol/l).
Dosage
The dosage of Caninsulin that is administered to a diabetic rabbit should be
based on the level of control of blood glucose concentrations. An initial dose
of 1 unit per kg once daily is recommended. On the basis of the efficacy, a
higher dose (up to 3 units/kg once daily) or two doses per day can be given.
Please take note that higher doses should not be administered for at least 2
days because a clear reaction to the insulin treatment is usually observed only
after this amount of time. A higher dose given too soon might cause sudden clinical
signs: polyuria, polydipsia and polyphagia, as well as the return to normal
of the rabbit. The desired blood sugar concentration is between 120 and 250
mg/dl (6.7 and 13.9 mmol/l). Lower levels increase the danger of hypoglycaemic
episodes.
Feeding
The food of rabbits is naturally full of crude fibre; rabbits eat small portions
throughout the day. The food of a diabetic rabbit must consist of hay, high
quality green forage and little ready-made food. Ready-made food is often very
energy rich and contains too little crude fibre. Feeding diabetic rabbits titbits
and sweet fruit (e.g. apple, pear and berries) is not advised.
Control
Rabbits that are doing well on insulin treatment should be checked every three
months. The blood and urine glucose concentrations should be measured. It is
also normal to check the rabbit’s general well being and its diet.
References
Ewringmann A, Göbel T (1998) Diabetes mellitus bei Kaninchen, Meerschweinchen
und Chinchilla. Kleintierpraxis 43, 337-348.
Ewringmann A & Göbel T (1998) Untersuchung blutchemischer Parameter bei
Heimtierkaninchen. Kleintierpraxis 43, 447-452.