Objectives

• Discuss the etiology and progression of the diabetes in the cat

• Compare and contrast the new insulins on the market

Key Points

• The etiology of diabetes in cats is related to insulin resistance and glucose toxicity resulting in impairment of insulin secretion and beta cell destruction

• PZI is no longer available, but glargine has been promising in cats, especially newly diagnosed diabetics

• Dedicated owners may find home monitoring an attractive alternative when used in conjunction with monitoring of clinical signs and periodic fructosamine levels

Background

Cats are true carnivores and as such have a metabolism specifically adapted to high protein meals:

• Proteins (amino acids) provide the substrate for gluconeogenesis;

• Cats continue to produce glucose even during the fed state;

• Cats appear to be naturally "insulin resistant" as a means of maintaining euglycemia during long-periods of fasting that occur in the wild;

• Cats have limited function of glucokinase, hexokinase and glycogen synthetase which are enzymes used to convert glucose to the glycogen.

These metabolic strategies mean that they are less efficient at "sopping up" post-prandial glucose loads that occur with high carbohydrate meals. Commercial dry diets, by virtue of the processing that must occur to create a dry diet, contain higher quantities of carbohydrates than the comparable canned diet. In order to deal with the post-prandial hyperglycemia, the pancreas secretes ever increasing levels of insulin, for a time, to maintain euglycemia. Obesity can add to the insulin resistance and stimulate additional insulin secretion. There are several problems with this scenario of hyperglycemia and initial hyperinsulinemia. With increased insulin secretion, there is increased amylin secretion, a molecule that is co-secreted with insulin. Amylin is then deposited back into the islet cells as amyloid causing destruction over time of the beta cell leading eventually to decreased insulin secretion. Hyperglycemia causes "glucose toxicity" in which glucose receptors on the beta cell become "desensitized" from chronic stimulation, thus impairing insulin secretion from the beta cell, again ultimately leading to decreased insulin secretion and exacerbation of hyperglycemia. This unique metabolism makes the cat predisposed to Type II diabetes given the twin evils of obesity and high carbohydrate diets. With on-going destruction of the beta cells, Type I diabetes can eventually occur.

Insulins

Insulin species that are available are beef, pork and human recombinant. Feline insulin differs from human insulin by 4 amino acids, from pork by 3 amino acids and from beef by 1 amino acid. This is why beef/pork mixtures such as PZI have been preferred in the past. Fortunately, even though human and pork insulins are slightly different from feline insulin, anti-insulin antibodies are uncommon and account for less than 5% of cases of insulin resistance in diabetic cats. Types of insulins for use in cats include:

Lente

A crystalline insulin which owes its duration effect to the size of the crystal molecule (larger equals longer duration – regular insulin, for example, is a small crystalline molecule) Human-recombinant insulin products such and Humulin-L have gone off the market due to lack of demand since the advent of newer recombinant insulins. The current Lente veterinary product is pork source Lente (Vetsulin®, Caninsulin®) can be used in cats. Vetsulin is manufactured at a concentration of 40 U/ml and requires U-40 syringes. It is important to take care when switching to a U-100 insulin to avoid overdosing (if the owner does not also change to U-100 syringes). Lente should be dosed on a BID schedule.