Therapeutic goals for otherwise healthy diabetic cats

The principle goals of treating diabetes in cats are to correct the major clinical signs of diabetes (weight loss, polydipsia / polyuria, and polyphagia or inappetence), and to prevent diabetic ketoacidosis. Additional goals are to minimize the risk of hypoglycaemia by appropriate dose adjustment of insulin or oral hypoglycaemic agents. Appropriate therapy of cats may also lead to diabetic remission, although currently it is not possible at diagnosis to predict which cats are more likely to go into remission. Treatment that is most effective in correcting hyperglycaemia is more likely to lead to remission by facilitating the recovery of the pancreatic cells from glucose toxicity.

Treatment modalities

Diet

General considerations

In cats, post-prandial hyperglycaemia is very prolonged (up to 18-24h) in cats fed typical cat foods. Therefore there does not seem any need to match the timing of the insulin dose to meals, which is important in the control of blood glucose in human diabetics.

Diabetic cats should be fed a low carbohydrate-high protein diet to minimize post prandial glucose fluctuations. Bodyweight should be monitored, as once the diabetes is stabilised with therapy, bodyweight often increases. If the cat starts to become overweight, its calorie intake should be restricted but maintained on a low carbohydrate-high protein diet rather than swapping to a high carbohydrate weight loss diet.

Oral hypoglycaemics

Approximately 5-30% of diabetic cats achieve good clinical control with oral hypoglycaemic drugs. The oral sulphonylurea hypoglycaemic drug glipizide has been used successfully in the treatment of diabetic cats. The dose of glipizide is 2.5mg bid, regardless of the bodyweight of the cat.

As glipizide may cause transient elevation of liver enzymes and in some cases icterus, monitoring of hepatic enzymes is recommended during glipizide treatment, which adds to treatment costs.

There are a variety of other oral agents that are used in humans for the treatment of diabetes. A preliminary report of a comparative study using PZI insulin with and without concurrent vanadium administration (45mg orally once daily), showed that vanadium may reduce the required dosage of insulin. Acarbose has been used to decrease GIT absorption of glucose but did not appear to add a beneficial effect when combined with a low carbohydrate-high protein diet.

Insulin

The mainstay of treatment in diabetic cats is injectable insulin. The choice of insulin for diabetic cats centres around minimising the number of injections required each day, while still achieving adequate diabetic control. Insulins used for maintenance are those classified as either intermediate duration (lente or NPH {Isophane}), or long acting (Ultralente, protamine zinc insulin {PZI} or glargine). Despite the variation in insulin types used, no correlation was found between the type of insulin and diabetic control.

The lente insulins have a more predictable onset and duration of effect in cats than the longer acting insulins. Porcine lente insulin is available in many countries as a proprietary veterinary product, Caninsulin (Intervet International BV, The Netherlands) at a concentration of 40 IU/ml, which is preferable to 100 IU/ml for use in cats. Porcine lente insulin needs to be given twice daily in all diabetic cats except those with substantial endogenous insulin secretion and mild hyperglycemia. Caninsulin provides good to excellent clinical control in the majority of cats, although the occasional cat has a very early peak of action (3 hours or less), and has better control with a longer-acting insulin. NPH insulin has a similar but slightly shorter duration of action than lente insulin, and usually is given twice daily.

Human Ultralente insulin can be used once daily in many cats, but the majority of cats (92%) will require twice daily treatment. Because of this dosing frequency and 100 IU/ml concentration, it does not offer an advantage over lente or PZI insulin, especially if either of these are available at 40 IU/ml. It is more variable in action than lente or NPH.

The long-acting insulin PZI insulin can be used once daily in 50% of cats, but is noted for its unpredictable onset and duration of action. Prolonged marked hypoglycaemia may occur in some cats on PZI, and in some cats, glycemic control is poor, possibly because of inadequate absorption. PZI is particularly useful for cats in which the duration of action of lente insulin is too short to give adequate glycaemic control, and when owners are unwilling to give twice daily injections. Many cats have good to excellent clinical control with PZI, but cats which do not achieve good control should be tried on a shorter acting insulin such as lente, before the poor control is attributed to insulin resistance.

The new insulin analogue, glargine, is a long-acting insulin released for human use. Initial data shows that like other long-acting insulins, there is considerable variation between cats and within the same cat in onset, duration and degree of action, and prolonged hypoglycaemia is a risk. In cats is not peakless, as suggested by the marketing information released for humans. However, initial data indicates it is likely useful in diabetic cats and can be given once or twice daily, depending on the individual cat

In some cats, blood glucose does not fall significantly and control of clinical signs is poor when using the longer-acting insulins (human or bovine Ultralente, or PZI) insulin), even when doses of 1.5 IU/kg or greater are being used. A change to a better absorbed, shorter acting insulin (lente or NPH) may improve diabetic control in these cats. Alternatively, glycine may be trialed.

Starting dose of insulin

The type of insulin chosen, and the baseline blood glucose of the cat determine the initial dose of insulin. Insulins which have a longer duration of action do not tend to lower the blood glucose as much as the same dose of a shorter acting insulin. Our current regime is to start cats which have marked hyperglycaemia (blood glucose >= 20mmol/l) on 0.5 IU/kg insulin when using porcine lente, and to start cats with less pronounced hyperglycaemia (blood glucose < 20mmol/l) on 0.25 IU/kg insulin. If the blood glucose cannot be measured, then it is best to start with a minimal total dose of insulin of 1 IU/cat.

A suggested regimen is to re-evaluate the blood glucose response every two to four weeks (or immediately if clinical hypoglycaemia occurs) until good control is attained. In the early stages of treatment, a nadir of 5.0 to 9.0 mmol/l is a suitable target. If the nadir of blood glucose is above this level, the insulin dose is increased by 1 IU total dose. If clinical hypoglycaemia occurs, the insulin dose should immediately be decreased by 50%, and a serial blood glucose curve performed for the new dose.

If lente or NPH insulin is being used and diabetic control is poor, two circumstances may warrant a change to longer acting insulin (PZI or glargine). Firstly, if the insulin is having a rapid peak of action (within 2-3 hours) and a short duration of effect (6-7 hours), and/or secondly if a low nadir blood glucose of (<3.5 mmol/l) is occurring despite the mean blood glucose remaining high (above 15 mmol/l).

Monitoring diabetics

Evidence for good clinical control includes an active cat with a healthy appearance, a stable, normal bodyweight, and levels of polydipsia and polyuria acceptable to the owner and veterinarian. Water intake can be measured at home or in hospital, and is a better indicator or mean blood glucose than fructosamine. Water intake may vary substantially from day to day, so measurement for more than a single day, and preferably over a week. A water intake of less than 20 ml/ kg bodyweight/ 24 hours indicates exemplary diabetic control. Most cats with good control drink less than 80 ml/ kg bodyweight/ 24 hours. Other clinical signs such as a stable normal bodyweight, and the presence or absence of lethargy should also be monitored.

High fructosamine levels (> 500 μmol/l) indicate a problem, but not necessarily whether the insulin dose needs to be increased or decreased. Making insulin dose rate changes on the basis of fructosamine measurements should be done with caution, as the fructosamine level does not give an indication of the nadir blood glucose. However, fructosamine may be a useful marker where stress or fractiousness makes an accurate serial blood glucose curve unobtainable.

Urine glucose also does not give information about how an insulin dose should be changed, and is most useful for indicating or predicting diabetic remission. If the cat becomes aglycosuric, this may indicate diabetic remission has occurred, and the insulin can be discontinued for several days while the urine glucose is monitored daily. If glycosuria recurs, it may be necessary to perform a serial blood glucose curve to determine the subsequent insulin dose.

In general, the best glycemic control is obtained in the majority of cats by using PZI or glargine twice daily combined with a low carbohydrate-high protein diet.

References

1.  Feldman EC, Nelson RW, Feldman MS Intensive 50-week evaluation of glipizide administration in 50 cats with previously untreated diabetes mellitus. J Am Vet Med Assoc 210: 772, 1997.

2.  Greco DS: Treatment of non-insulin dependent diabetes mellitus with oral hypoglycemic agents In 15th Annual Forum of the American College of Veterinary Internal Medicine, Lake Buena Vista, Florida, USA.1997, 252

3.  Nelson RW (2000) Diabetes mellitus. In Ettinger SJ, Feldman EC (Eds.), Textbook of veterinary internal medicine (Vol. 2, pp. 1438): W.B Saunders Company.

4.  Rand JS and Martin GJ: Management of feline diabetes mellitus: Vet Clinics of Nth America, 31(5):881-913