Q: Please review management of difficult-to-regulate diabetic cats.

A: Dr. Anthony C.G. Abrams-Ogg gave an excellent lecture on Difficult-to-Regulate Diabetic Cats at the 2008 American College of Veterinary Internal Medicine (ACVIM) Forum in San Antonio. Here are some relevant points:

The goal in treating diabetic cats is to regulate blood glucose levels. What constitutes poor regulation depends on what is considered acceptable regulation. For this discussion, difficult regulation in a cat is defined as failure to consistently control hyperglycemia, using a normal dose of an oral hypoglycemic agent (OHA) or insulin, for a sufficient part of the day to minimize PU/PD, normalize appetite, promote weight gain and activity, and lower fructosamine ± glycosylated hemoglobin levels.

Difficult regulation occurs in different forms:

1) Consistently bad days with persistent hyperglycemia

2) Inconsistent regulation, where the cat has good and bad days (the extreme is "brittle" diabetes with recurrent fluctuations between hyperglycemia/ketoacidosis and hypoglycemia)

3) Insulin resistance (IR), where unusually high doses of insulin are required to achieve regulation.

The diagnostic approach to the poorly regulated cat should be systematic and the potential causes critically reviewed for each case, but the specific approach will vary with the individual case depending upon the extent of initial evaluation for concurrent diseases, clinical signs, current therapy and owner desires. In some cases knowing that concurrent/underlying diseases have been ruled out by exhaustive screening will facilitate patience with adjustments in therapy. In other cases, where there are no obvious signs of a concurrent disorder, an owner may wish to try adjustments in therapy prior to extensive diagnostic testing. Ideally only one change in management should be made at a time.

Causes of difficult regulation include:

1) Problems with dietary therapy

2) Problems with OHA therapy

3) Problems with insulin therapy

4) Disorders causing insulin resistance.

More than one of these may be occurring in an individual case.

Problems with dietary therapy

The diet is the most important medical therapy for diabetes mellitus in cats. There is mounting evidence that reducing carbohydrate and increasing protein content of the diet will improve regulation (and increase the likelihood of resolution of diabetes), and early dietary change is recommended for cats with persistent hyperglycemia without another obvious cause. It is not known if dietary change will always improve inconsistent regulation and reduce insulin requirements when there is therapeutic insulin resistance, but it is a rational maneuver. Grain-free or raw-meat diets should be considered for regulating diabetes mellitus in cats.

Feeding schedule is important in humans and in dogs, primarily because of post-prandial hyperglycemia (PPH), and changing feeding schedule has improved regulation in some dogs. This does not appear to be an important cause of poor regulation in cats. Cats tend to eat frequently and acute PPH does not appear to be an important event, especially if the diet's carbohydrate content is reduced. The occasional cat with polyphagia that consumes its food in one sitting may have acute PPH, which may be confirmed with a blood-glucose curve. Dividing the daily food into more frequent feedings (an automated feeder may help) is one solution.

Problems with OHAs

The cat may not be getting its medication consistently, either because it is difficult to pill or is not eating the medication in its food. This should be reviewed, and the cat may be hospitalized for treatment and effect confirmed with blood-glucose measurements.

Oral hypoglycemic agents (OHAs) may be ineffective. Glipizide is used most often, with most cats responding within three months. Failure to respond after that time suggests there is insufficient functional beta-cell mass, and cats failing therapy are usually treated with insulin.

There are anecdotal reports of response to other OHAs, but, as with glipizide, failure of response in most cases is probably due to ineffectiveness of the drug.

Acarbose and dietary management has resulted in regulation, and acarbose have been anecdotally effective in improving regulation in cats receiving other treatments, but it is unlikely to be effective on its own, especially given the nature of PPH in cats. If there is a specific cause of IR, the role of continuing OHA therapy without initiating insulin while addressing the underlying disorder has not been defined.