Therapy for diabetes should be instituted as soon as possible after diagnosis. The main goal of therapy is to achieve normal blood glucose levels without the need for insulin therapy, commonly termed diabetic remission. For cats not achieving remission, the goals are to resolve clinical signs while avoiding low blood glucose (hypoglycaemia). Administration of insulin and dietary modification are the principal therapies used for management of diabetic cats. The use of long-acting insulins, particularly glargine and detemir, and low-carbohydrate diets allows better control of blood glucose levels and increases the probability of remission, while minimising the chance of hypoglycaemia. However, legislation in many European countries requires that a licensed veterinary product such as lente insulin be used first.

Feeding

Diets low in carbohydrate reduce postprandial hyperglycaemia and insulin concentrations in healthy cats. Initial data from diabetic cats also suggest that low-carbohydrate-high-protein diets result in better control of clinical signs, reduced insulin requirements and increased rates of diabetic remission. During the first few weeks of treatment, diabetic cats may have a reduced appetite, and if they refuse these low-carbohydrate diets, they should be offered any palatable food. However, a commercial low-carbohydrate diet should be used in diabetic cats, unless contraindicated by other disease. Cats with advanced renal disease will require a renal diet which is high in carbohydrate. Acarbose may be used to reduce glucose absorption from the gastrointestinal tract; however, it is not very successful in decreasing blood glucose concentrations in cats which are grazing throughout the day; it also may cause flatulence and diarrhoea.

Given the frequency of renal disease in diabetic cats, attention should be paid to the phosphate content of the diet. Many grocery-line low-carbohydrate-high-protein feline maintenance diets are high in phosphate. Cats in stage 1 or 2 renal failure which do not require protein or phosphate restriction should be placed on a low-carbohydrate diet formulated for feline diabetics that is low in phosphate; high-phosphate, ultra-low-carbohydrate diets are best avoided.

Obesity in cats markedly reduces insulin sensitivity and increases the need for insulin. Hence, energy fed should be restricted so weight loss occurs in obese cats at a rate of 1–2% loss of bodyweight per week. As blood glucose levels after a meal are lower in cats eating a low-carbohydrate diet, it is suggested that diets with less than 20% of energy from carbohydrate (e.g., Hills m/d, Purina dm) should be used for obese diabetic cats during the calorie-restriction phase. In some cats, diabetic remission is obtained after weight loss.

Acarbose

Acarbose is an α-glucosidase inhibitor that reduces intestinal glucose absorption and is generally not effective alone in the treatment of feline diabetes, but can be used in conjunction with insulin and/or other oral agents. They work best if the cats are meal fed.

Insulin Therapy

Long-acting insulin therapy remains the preferred initial and long-term treatment of choice for diabetes mellitus in cats. Achieving good glycaemic control with intermediate-acting potent insulins such as NPH and lente is often difficult, and increases the risk of clinical hypoglycaemia. The long-acting insulins glargine and detemir provide better glycaemic control, reduced risk of clinical hypoglycaemia and a higher probability for remission when given twice daily and combined with a low-carbohydrate diet.

In many parts of Europe, veterinary-licensed insulin, such as porcine lente insulin, is required to be administered first in newly diagnosed diabetic cats, but remission rates are often in the order of 30% compared to over 80% in newly diagnosed diabetic cats treated with glargine or detemir and a low-carbohydrate diet. These latter insulins are safe and effective in treating feline diabetes and are the preferred insulins in newly diagnosed diabetic cats.

Glargine is a new long-acting human synthetic insulin. Glargine is a clear aqueous solution in 100 IU/ml vials and cannot be mixed or diluted. It is marketed for human patients as a very long-acting 'peakless' insulin, with regard to its glucose-lowering effects. In healthy cats, administering glargine twice daily produces a longer effect compared to once daily, and better control of blood glucose levels. As excellent control of blood glucose helps produce diabetic remission, twice daily dosing is recommended.

Glargine can be safely instituted at 0.5 IU/kg q12h and serial blood glucose curves should be obtained daily for 3 days either in hospital or at home. We have found it often takes 3–5 days for a good glucose-lowering effect to be seen in the glucose curves, possibly because of the long duration of action and carry-over effect of glargine. Almost all cats will need to have their initial dose reduced within 2 weeks and many will achieve remission within 4 weeks.

Detemir is a new long-acting synthetic insulin. Detemir results in similar remission rates and time to remission as glargine, but the median maximum dose used (1.75 IU/cat q12h) is about 30% less than with glargine (2.5 IU/cat q12h).

Oral Hypoglycaemic Drugs

The use of oral hypoglycaemic drugs to treat feline diabetes has been limited for a number of reasons. Many owners find administering tablets more difficult than injecting with insulin. Drugs which stimulate insulin secretion (e.g., sulphonylureas) require adequate pancreatic beta cell function to be effective. If used as a sole therapy, remission rates are < 20%, and therefore it should only be used as a sole therapy in the situation where the owner would have the cat euthanased rather than give insulin. It should be combined with a low-carbohydrate diet.

Monitoring Therapeutic Efficacy

Response to treatment can be evaluated in a number of ways, and no individual modality should be used alone to adjust therapy. A combination of owner measurement of blood glucose, clinical signs and changes in bodyweight and water intake are often the best indicators of glycaemic control.

Monitoring and adjusting insulin dose when using glargine or detemir should be based on a number of parameters including: pre-insulin and nadir glucose concentration; water intake; urine glucose concentration; and clinical assessment. We have found pre-insulin glucose concentrations measured at home an excellent tool to safely modify daily doses of glargine or detemir.

Insulin dose may be reduced sequentially as indicated by blood glucose concentration, urine glucose and water intake. Even if blood glucose levels are normal, it is recommended that insulin is not withdrawn within 2 weeks of commencement of therapy. If insulin is withdrawn, the cat is carefully monitored to ensure continued remission. It is also imperative that cats remain on a low-carbohydrate diet with calorie control to prolong the remission period. Newly diagnosed diabetic cats that have good glycaemic control within the first few weeks of therapy are very likely to go into diabetic remission. Cats that have been long-term diabetics (> 6 months) are less likely to go into remission.

Cats in remission should be carefully monitored. Approximately 25–40% of cats in remission will relapse and require insulin again. Cats which relapse should have insulin reinstituted as soon as fasting glucose concentrations are persistently 10 mmol/l or higher. If insulin is reinstituted early, better glycaemic control with smaller insulin doses is achievable and a second remission is more likely.

Conclusion

Although in many parts of Europe, lente insulin is required to be administered first in newly diagnosed diabetic cats, glargine and determir are safe and effective in treating feline diabetes and are the preferred insulins in newly diagnosed diabetic cats. Cats treated with lente insulin that do not achieve remission in 4–6 weeks should be changed to glargine or detemir to facilitate remission before there is permanent loss of beta cells. High remission rates are expected in newly diagnosed cats when combined with a low-carbohydrate diet and twice daily injections.

With thanks to Rhett Marshall BVSc, MACVS.

References

Reference list provided upon request. Selected articles are available on our website: www.uq.edu.au/vetschool/centrecah