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Treatment of diabetes (Proceedings)

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Aug 01, 2011

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. Porcine insulin, which is identical to canine insulin in its amino acid structure, is available for use in dogs in some countries, but, unfortunately, no specific feline insulin formulation is currently available. Human, bovine, or porcine insulins are used in treating both diabetic cats and dogs. Data concerning the pharmacokinetics and pharmacodynamics of insulin in dogs and cats are difficult to interpret. Most published studies have been conducted in normal animals, and some have been done in animals 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 animal to animal. In fact, there is no reasonable way to predict the kinetics of an given insulin preparation in any given patient.

Neutral protamine Hagedorn (NPH) insulin (Humulin-N®), porcine lente insulin (Vetsulin®), and protamine zinc insulin (ProZinc®, PZI) have been used commonly to treat diabetes mellitus in cats. In recent years, insulin glargine (Lantus®) has become probably the most commonly used insulin preparation in cats, despite relatively little published evidence supporting its use. Recently, another insulin analog, insulin detemir (Levemir®), has received some attention among veterinary researchers and feline practitioners.

In dogs, porcine lente insulin and NPH are used most commonly.

NPH and lente

NPH is considered an intermediate-acting insulin, and is available as a human recombinant product. NPH is used commonly in animals with diabetes, and is typically given subcutaneously 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 currently marketed and labelled for use in dogs and cats. Currently available veterinary products are Vetsulin® (U.S.) and Caninsulin®(Europe, Australia, Canada). Vetsulin, however has been largely removed from the U.S. market and is only available through special arrangement with the manufacturer. While identical to canine insulin, porcine insulin is dissimilar in amino acid sequence when compared to feline insulin, but it is no more divergent (by 3 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.1 A recent study suggested the duration of porcine lente is shorter than either PZI or glargine in cats.

Protamine zinc insulin

PZI has been used extensively in feline diabetes. It is typically given subcutaneously twice daily, with a starting dose of 1-3 U/cat. 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 veterinary PZI product, a preparation of 90% beef insulin and 10% pork insulin, was removed from the market two years ago, but a human recombinant protamine zinc insulin product approved for feline diabetics was introduced in 2009. This insulin was the subject of a multi-center clinical trial reported by Nelson et al.3 In that study of 133 diabetic cats, "good" glycemic control was defined as an average blood glucose concentration below 200 mg/dl during a 9-hour blood glucose curve. A glucose nadir of less than 150 mg/dl was also considered good, as was a serum fructosamine concentration lower than 450 μmol/L. In that study, after 45 days of twice daily treatment with PZI, 60 percent of cats exhibited good glycemic control based on the glucose nadir. Seventy-five percent of cat owners reported improved polydipsia, and 79 percent reported improved polyuria.

PZI is also available from compounding pharmacies.. Care should be taken when using PZI acquired from compounding pharmacies because of quality control issues.