CVC Highlight: Insulin therapy for diabetes mellitus in dogs and cats: Ensuring your chances of success

The variety of insulins to treat diabetes mellitus in veterinary patients is ever-changing. Make sure you're aware of all your options to ensure your patients receive the best treatment.

J. Catharine Scott-Moncrieff

UPDATE ON AVAILABLE INSULIN PRODUCTS

Following is a practical list (FDA-approved manufacturer's labels may be different) of options for insulin therapy. Veterinary-formulated insulin products (ProZinc—Boehringer Ingelheim Vetmedica; Vetsulin—Intervet/Schering-Plough Animal Health; Vetsulin is not currently available) are 40 U. Human-formulated insulin products are 100 U. It is imperative to match the product concentration to the appropriate syringe.

Short acting

Regular insulin—only used in sick diabetic patients

Moderate acting

NPH (isophane)

• Onset 0.5 to three hours

• Duration four to 10 hours (dogs), four to 12 hours (cats)

Lente

• Amorphous insulin and crystallized insulin in zinc acetate buffer

• Mixture of 30% semilente and 70% ultralente—can see two nadirs on blood glucose curve

• Not currently available in the United States but may be back on the market soon.

Long acting

PZI—protamine zinc insulin

• FDA approved for use in cats

• Zinc and protamine (from trout semen) delay absorption

• Onset one to four hours

• Duration six to 28 hours (dogs), six to 24 hours (cats)

Glargine

• Forms microprecipitate at physiologic pH resulting in slow release over 24 hours

• Cannot be mixed with anything

• Time to nadir is long (11 to 16 hours)

Detemir

• Not a first-line choice

• Long lasting (> 24 hours)

• High risk for developing hypoglycemia

• Dose range in dogs much lower than for other insulin products (0.07 to 0.23 U/kg)

Compounded insulin

The use of compounded insulin products is highly controversial. The perceived advantages of compounded insulin are lower cost, greater availability, a wide range of concentrations, and great customer service. That being said, there has been strong resistance to their use from veterinary specialists, who recommend against their use. (Anecdotally, these specialists have had problems with these products.)

An extensive study involving evaluation on a monthly basis of 12 compounded PZI insulin products and one from a manufacturer was conducted to help put an end to the speculation about these insulin products.1 Two vials from each batch were sent for testing every two months for four months (one blinded, one original). Many of the compounded products were found to have low potency, extremely high interlot variability, incorrect pH, free insulin in the supernatant, and incorrect zinc content. These findings support those specialists that recommend that compounded insulin should not be used.

INSULIN THERAPY IN DOGS

For newly diagnosed diabetic dogs, NPH at a starting dose of 0.5 U/kg given twice daily is recommended. Long-acting insulins such as PZI or glargine are unpredictable in dogs and not generally recommended. A bit more information is available on the use of detemir in dogs, but careful dosing is required, and the risk for developing hypoglycemia is high. Insulin mixtures should be reserved for difficult cases.

INSULIN THERAPY IN CATS

Long-acting insulin products are a suitable first choice for treatment of diabetes mellitus in cats. The starting dose for newly diagnosed patients is 0.25 to 0.5 U/kg (or 1 to 3 U/cat). A wide range of doses are used to achieve glycemic control, so start low and work up.

Studies have reported that PZI is effective (80% to 90%) in establishing glycemic control.2,3 Glargine is also effective in achieving good glycemic control in cats.4 Several studies have attempted to compare the rates of remission based on the type of insulin used, and while in small studies there has been evidence that cats treated with glargine may be more likely to achieve remission, this finding needs to be replicated in larger studies.5

Cats should be carefully monitored for the development of hypoglycemia because of the possibility of remission, and a blood glucose curve should be performed five to 14 days after any change in insulin formulation or dose.

Since intermediate-acting insulin such as Lente are generally more potent than the long-acting insulin products, they may be a better choice for patients with concurrent illnesses that can cause insulin resistance or that may make cats prone to ketosis.

Regardless of insulin formulation, twice-a-day dosing is more likely to result in good glycemic control. In addition, once-a-day dosing can increase the risk for hypoglycemia.

MONITORING INSULIN THERAPY IN DIABETIC PATIENTS

Always wait a minimum of seven days before increasing an insulin dose, and spot-check the blood glucose concentration in the first 24 to 48 hours after any change to detect hypoglycemia.

To evaluate a patient's response to insulin therapy, be sure consider changes in clinical signs, blood glucose curves, urine glucose concentrations, and fructosamine concentrations. Therapy changes should be based on all of these parameters. An increased blood glucose concentration may be short-lived, so it is important to look at all of the information before changing insulin dosage or formulation. Then, adjust the dose as needed and reevaluate.

Home monitoring is advisable in many cases, but some owners will go overboard with their level of blood glucose monitoring, so make sure that you are seeing those patients in the clinic from time to time and advising owners appropriately. It is also good to remember that all blood glucose meters are not the same. The ease of use and blood volume required can vary from brand to brand, so become accustomed to one type and be consistent. Another consideration is that human blood glucose meters have a built in bias at lower concentrations. They are still useful for dogs and cats, but this bias must be taken into consideration. Based on a University of California-Davis study, the most precise meters for dogs and cats are the Alpha Track (Abbott) and the One Touch Ultra (LifeScan).6

Remission in cats

Diabetes mellitus in cats can be transient or intermittent. Several studies have reported spontaneous remission of diabetes in cats after weight loss and good glycemic control was achieved.4,5 However, the rates of remission in these studies varied widely (17% to 64%). Diabetic cats that achieve remission should not be considered normal; care must be taken to watch for the return of clinical signs. The length of remission varies from one to two months to the rest of their lives. Many cats will go in and out of remission, so we should be careful in discussing the possibility of remission with owners of diabetic cats since a half to a third of cats that go into remission will relapse.4,7,8

A WORD ON DIETARY MANAGEMENT

The goal of dietary management in diabetic patients is to minimize postprandial fluctuations in blood glucose concentrations and potentiate the action of insulin. In cats, obesity is one of the major contributing factors to the development of diabetes mellitus, so weight loss in these patients is a large component of therapy.

Always consider concurrent conditions before altering a pet's diet. Generally, animals receiving therapeutic diets for other conditions should not be switched to a diet that manages their diabetes. Studies support the feeding of high-carbohydrate, high-fiber diets to diabetic dogs.9 In cats, starting with a low-carbohydrate, high-protein diet and transitioning to a high-fiber diet if there is poor response to the low-carbohydrate diet is a good approach.

J. Catharine Scott-Moncrieff, MA, Vet MB, MS, DACVIM, DECVIM

Department of Veterinary Clinical Sciences

School of Veterinary Medicine

Purdue University

West Lafayette, IN 47907

REFERENCES

1. Scott-Moncrieff JC, Moore GE, Coe JE, et al. Characteristics of commercially manufactured compounded protamine zinc insulin. J Am Vet Med Assoc 2012: in press.

2. Nelson RW, Lynn RC, Wagner-Mann CC, et al. Protamine zinc insulin for treatment of diabetes mellitus in cats. J Am Vet Med Assoc 2001;218(1):38-42.

3. Nelson RW, Henley K, Cole C. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet Intern Med 2009;23(4):787-793.

4. Roomp K, Rand J. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. J Feline Med Surg 2009;11(8):668-682.

5. Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves diabetic control and results in higher probability of remission than protamine zinc and lente insulins. J Feline Med Surg 2009;11(8):683-689.

6. Cohen TA, Nelson RW, Kass PH, et al. Evaluation of six portable blood glucose meters for measuring blood glucose concentration in dogs. J Am Vet Med Assoc 2009;235(3):276-280.

7. Sieber-Ruckstuhl NS, Kley S, Tschuor F, et al. Remission of diabetes mellitus in cats with diabetic ketoacidosis. J Vet Intern Med 2008;22(6):1326-1332.

8. Zini E, Hafner M, Osto M, et al. Predictors of clinical remission in cats with diabetes mellitus. J Vet Intern Med 2010;24(6)1314-1321.

9. Nelson RW, Duesberg CA, Ford SL, et al. Effect of dietary insoluble fiber on control of glycemia in dogs with naturally acquired diabetes mellitus. J Am Vet Med Assoc 1998;212(3):380-386.