There is no best insulin, as glycemic control often varies from patient to patient. For example, one hyperlipidemic diabetic Miniature Schnauzer may be regulated better using an insulin mixture (70/30 NPH-Regular) given BID, as compared to NPH BID, whereas another diabetic hyperlipidemic Miniature Schnauzer may be controlled relatively well using Lente insulin BID. In some diabetic cats, adequate diabetic control can be achieved using human NPH or Lente BID, whereas optimal glycemic control in others is best achieved using protamine zinc insulin (PZI) or glargine insulin.

Insulin therapy remains the preferred initial and long-term treatment of choice for diabetes mellitus (DM) in the cat.

Type of insulin to use and frequency of administration
In general, therapy for uncomplicated DM should be initiated with either a long-acting insulin preparation (PZI, Ultralente insulin, or glargine insulin) given once or twice daily, or an intermediate-acting insulin (Lente or NPH) given twice daily. Because intermediate-acting insulins have a shorter duration of action than the long-acting insulins, once daily administration would rarely, if ever, satisfactorily control hyperglycemia in cats with diabetes.

Source of insulin (animal or human)
There are many different sources of commercial insulins. NPH and Lente may be of animal (beef, pork, or combination beef-pork) or of human synthetic origin. Ultralente and glargine are available as only of human origin, while PZI is only available as beef-pork insulin. Since cat insulin is most similar to beef insulin, this may be the insulin of choice (combination beef-pork is 90% beef insulin), although glargine insulin appears to be equally, if not more effective. However, the other insulin preparations (pork or human) also work well in most cats. Once a cat is stabilized on one source of insulin, the same type of insulin should be continued. If a change in insulin is contemplated or becomes necessary, it is important to realize that different types and brands of insulin may have different pharmacological properties, thereby necessitating insulin dosage adjustments.

Dose of insulin
When initiating therapy with an intermediate- or long-acting insulin, it is best to start with a relatively low dose (0.25 to 0.5 U/kg/day) and slowly increase the dose as needed. Most insulins are available in concentrations of 100 U/ml (U-100 insulin). However, PZI is available only in concentrations of 40 U/ml (U-40 syringes are available from the manufacturer). When using U-100 insulin, low-dose syringes (0.3 and 0.5 ml capacity U-100 insulin syringes) or dilution of insulin may be helpful for accurate dosing in cats with very low insulin requirements. Intermediate- or long-acting insulin preparations can be diluted in sterile water or isotonic saline or a pH-adjusted diluent obtained from the manufacturer. Because sterile water and isotonic saline may affect the shelf-life of insulin, a new supply of freshly diluted insulin should be prepared at least every 2 months.

Use of PZI Insulin in Cats
Protamine zinc insulin (PZI) is a long-acting preparation of beef/pork-source insulin used to treat diabetes mellitus in the cat. The product (PZI Vet) is available from Idexx Pharmaceuticals, Greensboro, NC as a 40 U/ml preparation; 40 U/ml insulin syringes are provided. While compounded PZI preparations are available from pharmacists at the request of veterinarians, they have not provided consistent glycemic control in diabetic cats, and are not recommended.

Based on a multicenter study with 67 diabetic cats, 90% had good diabetic control based on owner observation and serum fructosamine levels. Seventy-five percent of previously treated "hard-to-regulate" cats did well on PZI. The absorption kinetics, glucose nadirs, and duration of action of PZI is variable. In general, most cats require PZI twice daily. However, the blood glucose nadir occurred 9 hrs or longer after PZI administration in 25% of cats, suggesting that once a day administration of PZI may be effective for controlling hyperglycemia in some cats. Results of this study suggest that PZI insulin may be the initial insulin of choice for treating diabetic cats.

The initial recommended dosage is 1 U/cat/injection. Subsequent increases in the PZI dosage should be based on owner perception of their cat's response to treatment, urine glucose readings, changes in physical examination and body weight, and the results of blood glucose and serum fructosamine measurements.