What issues might be encountered when switching insulin?
Caution should be exercised when changing from one insulin product to another. Any change in insulin should be made cautiously and only under a veterinarian's supervision. Changes in insulin strength, manufacturer, type, mode of administration (syringe, insulin pen) and source (animal, human recombinant, analog) may result in altered regulation and lead to a change in dosage being required.
What is the approach if the insulin appears to have become ineffective?
Most apparent problems with insulin administration are simple. It is important to check if:
A blood glucose curve should be made taking samples every 2 hours for at least 12 hours, so that the blood glucose nadir is not missed. A single sample will not suffice in these cases. Measurement of fructosamine gives some indication of what has happened to the mean blood glucose concentrations over the preceding 2-3 weeks.
If there are signs of poor glycaemic control but the blood glucose nadir is between 5 mmol/L (or 90 mg/dL) and 10-12 mmol/L (or 180-216 mg/dL) then there may be either:
1. an administration or storage problem. Read more...
2. insulin resistance. Read more...
Administration and storage problems
1. Dose too high: if the blood glucose nadir is less than mmol/L (or 90 mg/dL) or blood glucose concentrations fall rapidly, there can be a rebound hyperglycemia (Somogyi effect). The blood glucose nadir (lowest concentration) should not be too low and there should not be large fluctuations between maximum and minimum blood glucose concentrations. A serial blood glucose curve with samples every 2 hours must be constructed to clarify this. A single blood sample at the time the blood glucose nadir is expected will not be sufficient.
2. Owners technique: It is important to observe the pet owner's technique, particularly when an animal has been well regulated for some time! Watch out for:
What is insulin resistance?
This should be suspected if the insulin requirements increase to more than 1.2 IU/kg once or twice daily in the dog, or more than 1.2 IU/ kg twice daily in the cat and particularly if requirements are greater than 2 IU/kg! Obvious causes of insulin resistance include obesity but after initial stabilization these should not result in a dramatic increase in insulin dose requirements. Remember that most dogs require insulin twice daily. In these animals an increase in dose may not produce an increase in duration of action but precipitate hypoglycemia and responsive hyperglycemia. If the duration of insulin action is less than 10-12 hours in a dog then it should receive insulin twice daily.
Read more about Rapid insulin metabolism
Read more about Insulin resistance
What is Vetsulin?
Vetsulin (porcine insulin zinc suspension) is the name of Caninsulin in the USA. Vetsulin is the first and only insulin approved by the US Food and Drug Administration for treating both canine and feline diabetes mellitus. Vetsulin and Caninsulin are produced by Merck Animal Health (MSD Animal Health outside North America) and are usually available only on prescription.
What type of insulin is Caninsulin?
Caninsulin is an intermediate-acting, lente insulin containing 40 IU per mL of highly purified porcine insulin. As a lente insulin, Caninsulin is an aqueous suspension containing approximately 30% amorphous and 70% crystalline zinc crystals in a neutral buffer of pH 7.35.
How long can the Caninsulin vial be kept after opening?
Before use, Caninsulin should be stored in a refrigerator and not frozen. It is usually advised that any pharmaceutical product should be disposed of around 1 month after opening. The Caninsulin label stated that the product should be used for 21 days, 28 days or 42 days after first opening, depending on the country. This is based on studies that were carried out looked at Caninsulin use for up to 42 days after first use. Many of the authorities that regulate medicines do not allow product labels that permit the use of sterile products for more than 28 days after first opening.
Can Caninsulin be pre-loaded into syringes?
Caninsulin can be preloaded into syringes for clients. However, this will be off label (extra label) use since it is outside the primary packaging (a glass vial). In addition, it may be difficult to re-suspend small volumes of insulin in a syringe.
What should Caninsulin look like?
Caninsulin is a mixture of two different types of insulin. Normally, after gentle mixing (invert (upend) several times) the vial, Caninsulin will appear uniformly milky and should not have any agglomerates (clumps or flakes) in it. Do not use the product if you see agglomerates in the vial after you have re-suspended the product.
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. Prior to first use, Caninsulin vials should be stored refrigerated and in an upright position.
Always check on the appearance of the Caninsulin before using it!
Can Caninsulin be diluted?
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, this may result in an alteration of the characteristics of the product (pharmacokinetics and Pharmacodynamics) in the animal. In addition, the stability of the new suspension is unknown. Dilution of Caninsulin would constitute off label (extra label) use.
Are there some guidelines for switching an animal from another insulin?
When an insulin change is necessary, one must be very cautious. Due to the varied nature of diabetes, it is difficult to have general guidelines; however, some recommendations can be made:
Important: It is important to check that the new insulin dose does not produce hypoglycemia. This can be done after the first dose is given around the time that the blood glucose nadir is expected. The animal should then be rechecked 5-7 days later and the dose adjusted further if required.
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 0.5 IU (tailor-made U40 insulin pen) or 1 IU (U40 insulin syringe) per injection are recommended. For more information see dose adjustment in cats.
Monitoring after conversion.
In all cases where the insulin dosage (type, dose or administration frequency) or method of administration (insulin syringe or tailor-made U40 insulin pen) has been changed, close monitoring of the animal is necessary.
Regulation is not always easy. The human factor can be a major source of problems. A new product at a different concentration, new syringe, insulin pen and/or new treatment schedule can be confusing, especially for the pet owner. Follow-up visits are highly recommended. For more information see Monitoring.
Important: In all cases, one should allow the animal to adapt to each new dose. At least 1 week or even longer is recommended. Larger or more frequent increases in dose are not recommended due to individual variation in insulin responsiveness.
What is the starting dose of Caninsulin for dogs?
Many specialists recommend twice daily Caninsulin in dogs at a maximum of around 0.5 IU/kg per dose once daily, with the recommendation to change to twice daily dosing if required. This is now the starting dose for Vetsulin in the US and in most countries for Caninsulin, although the older starting dose of 1 IU/kg plus a body weight related supplement is still approved in some countries.
It is expected that around two-thirds of dogs will require twice daily dosing. In other words, around one-third of diabetic dogs can be managed well on once daily treatment with Caninsulin. Use of Caninsulin once or twice daily must be made on an individual case basis.
What is potential diabetes mellitus and when does it occur?
Potential diabetes mellitus may be seen in female dogs during metestrus (diestrus). In the pancreatic islets in these dogs are still able to function but signs of diabetes appear as a result of insulin resistance caused by progesterone-induced production of growth hormone from the mammary gland. These dogs are not usually permanently diabetic but can become so if not treated appropriately (spaying as soon as possible). Potential diabetes mellitus shoul not be confused with diabetic clinical remission.
What is diabetic remission and when does it occur?
Diabetic clinical remission is a complete or partial disappearance of the clinical signs of diabetes usually in response to insulin treatment.
An entire or intact female dog presented with clinical signs of diabetes mellitus should be spayed (also known as ovariohysterectomy or ovariectomy) as soon as possible. These animals may require insulin treatment but the clinical signs of diabetes mellitus may be transient.
What results typically can be expected from Caninsulin therapy in dogs?
Diabetic dogs in clinical trials responded to porcine insulin zinc suspension in the following ways:
In most dogs, Caninsulin will produce adequate blood glucose control.
How does Caninsulin work in dogs?
A lente (intermediate-acting) form of insulin, Caninsulin contains approximately 30 percent amorphous insulin for rapid onset of activity, usually peaking about 4 hours after injection and lasting 8 hours in dogs. The remaining 70 percent of the formula is crystalline insulin which is absorbed more slowly and peaks around 11 hours after administration in dogs. In cats, the duration of action of Caninsulin is shorter, with the maximum duration of activity around 12 hours. This formulation allows for a more continuous utilization of glucose to support the body’s energy requirements. Caninsulin is administered subcutaneously once a day initially, although many dogs require twice-a-day administration for effective diabetes management. Cats require Caninsulin to be administered twice daily.
Can Caninsulin really be used only once-a-day in dogs?
Clinical studies have demonstrated that approximately one-third of diabetic dogs can be maintained adequately on once-daily doses of Caninsulin. The other two-thirds of dogs will require twice-daily administration of Caninsulin.
How often does Caninsulin need to be administered to dogs?
Initially, the dose should be given once daily concurrently with or right after a meal. The veterinarian should reevaluate the dog at appropriate intervals and adjust the dose in 10% increments based on clinical signs, urinalysis, and blood glucose concentrations until adequate regulation is attained. Twice-daily therapy should be initiated if the duration of insulin action is determined to be inadequate. If twice-daily treatment is initiated, each of the two doses should be 25% less than the once-daily dose required to attain an acceptable nadir.
The impact on blood glucose peaks may last from 14 to 24 hours, and approximately one in three diabetic dogs can achieve successful diabetes management with a single dose of Caninsulin per day. The treating veterinarian would need to determine the frequency of dosing for an individual dog.
How many dogs currently have diabetes?
It is estimated that roughly 1 in 500 dogs suffers from the signs of diabetes mellitus.
Is hind limb paresis a typical sign of diabetes mellitus in cats?
Hind limb weakness may be the result of feline diabetes.
This is also seen in a number of other conditions in cats:
How many cats currently have diabetes?
Estimates of the incidence of diabetes mellitus in cats range from 1 in 100 to 1 in 500.
How does Caninsulin work in cats?
A lente (intermediate-acting) form of insulin, Caninsulin contains approximately 30 percent amorphous insulin for rapid onset of activity. The remaining approximately 70 percent of the formula is crystalline insulin which is absorbed more slowly. This formulation allows for a more continuous utilization of glucose to support the body's basic functions. In cats, the peak activity following subcutaneous administration of Caninsulin occurs between 1.5 and 8 hours (with an average of about 4 hours), and a duration of activity varies between 8 and 12 hours. Caninsulin should be administered subcutaneously twice a day in diabetic cats.
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% and 65% or more when diabetic diets are fed in addition to insulin treatment.
What results typically can be expected from Caninsulin therapy in cats?
Cats are usually started on 1 to 2 IU of Caninsulin per injection twice daily. Glycemic control is evaluated based on clinical signs and blood glucose curves, supported by other laboratory results, such as fructosamine. Adjustment of the Caninsulin dose is made according to clinical improvement, as well as average blood glucose concentrations and blood glucose curve nadirs. Treated cats have significantly lower blood glucose concentrations and a reduction in hyperglycemia-associated clinical signs compared with pretreatment levels. Diabetic remission may also be observed.
How often does Caninsulin need to be administered to cats?
In cats, the initial recommended dose is 1 to 2 IU per injection, and the injections should be given twice-daily (BID) at 12-hour intervals. Initial dosing is based on a per animal basis. The duration of activity of Caninsulin in the cat is between 8 to 12 hours – this is shorter than in the dog. Peak activity level occurs between 1.5 to 8 (average of about 4) hours in the cat.