Insulin therapy in cats (Proceedings)
Few diseases are as frustrating for a veterinarian as diabetes mellitus. Realistically, control of hyperglycemia is rarely accomplished, and clinical signs of diabetes often persist. The landscape is changing in feline diabetes, however, and as clinicians learn more about new insulin preparations, diets, and treatment monitoring strategies, cats with diabetes may be better controlled.
There are many different types of insulin that vary with species of origin and with chemical modifications and formulations that affect onset and duration of action. Unfortunately, no feline insulin formulation is currently available, so human, bovine, or porcine insulin are used in treating diabetic cats. Data concerning the pharmacokinetics and pharmacodynamics of insulin in the cat are difficult to interpret. Most published studies have been conducted in normal cats, and some have been done in cats with diabetes. In either case, it is difficult to determine the effects of endogenous vs. exogenous insulin. Determinations of potency, time to peak activity and duration of activity, factors that influence choice of doses and dosing intervals, vary widely from cat to cat. In fact, there is no reasonable way to predict the kinetics of an given insulin preparation in any given patient.The most commonly used insulin preparations in cats are Regular insulin (Humulin-R™ ), NPH insulin (Humulin-N™ ), porcine lente insulins (Vetsulin™ ), PZI, Insulin glargine (Lantus™ ), and insulin detemir (Levemir™ ). Regular insulin is not used for chronic treatment of diabetes in cats, but is commonly used in the treatment of diabetic ketoacidosis.
NPH, PZI, and Lente
NPH is considered an intermediate-acting insulin, and is available as a human recombinant product. NPH is used commonly in cats with diabetes, and is typically given subcutaneously to cats twice daily. Lente insulin uses zinc as a positively charged ion on which to base insulin polymerization. Polymers are absorbed and metabolized slowly so that the onset and duration of lente insulin are extended beyond those of regular insulin. Human recombinant lente insulin has been removed from the United States market and is not longer available for use. Porcine lente insulin, however, has gained in popularity and is the only insulin currently marketed and labelled for use in the cat. Currently available veterinary products are Vetsulin™ (U.S.) and Caninsulin™ (Europe, Australia, Canada). Porcine insulin is dissimilar in amino acid sequence when compared to feline insulin, but it is no more divergent (by 4 amino acids) than is human insulin. Lente is typically given twice daily by subcutaneous injection, and studies in cats show it is a reasonable choice for treating diabetic cats(Martin and Rand 2001). A recent study suggested the duration of porcine lente is shorter than either PZI or glargine (Marshall et al 2008).
Protamine zinc iletin (PZI) has been used extensively in feline diabetes. This insulin preparation was widely available, but was largely removed from the human market in the 1990's. Recently, PZI preparations marketed for use in cats have once again become available. One product, PZIVet™ , a preparation of 90% beef insulin and 10% pork insulin, was removed from the market last year, but PZI is still available from compounding pharmacies. PZI is still a good choice for long-term treatment of diabetes in cats, and is typically given subcutaneously twice daily.
Insulin glargine is a genetically engineered insulin analog that has hormonal action identical to native insulin, has no known immunogenicity, and achieves long-lasting glycemic control while minimizing fluctuations in blood glucose concentration in many human diabetics. Glargine is based on human recombinant insulin with a few amino acid substitutions. Glycine is substituted for an asparagine residue at the amino terminal of the A chain, and two arginine residues are added to the end of the B chain (Figure 1). The result is a shift in the isoelectric point of the insulin molecule so that it is completely soluble at a low pH (around pH 4). The pH of interstitial fluid is approximately 7.4, and when glargine is injected into a patient, the insulin precipitates into hexamers that are inactive. These insulin hexamers are slowly broken down in the body to form active insulin monomers. The result is that the onset is gentle and the duration is long-lived. Because of the difference in pH, glargine cannot be mixed with other insulin formulations. Experience with using glargine in cats is growing (Weaver et al. 2006, Rand 2006), and many clinicians have had good success with its use. Glargine is best used twice daily subcutaneously.