Therapy for diabetes should be instituted as soon as possible after diagnosis with the main goal being remission; euglycaemia without the need for insulin therapy. For those cats not achieving remission the goals are to resolve clinical signs and avoid hypoglycaemia. Insulin and dietary modification are the principal therapies used for management of diabetic cats.

Feeding

Diets low in carbohydrate reduce postprandial hyperglycaemia and insulin concentrations in healthy cats. Data from diabetic cats also suggest that low-carbohydrate diets result in better clinical control, reduced insulin requirements and increased rates of diabetic remission. In the first few days of treatment, if cats refuse these low-carbohydrate diets, they should be offered any palatable food. However, a commercial low-carbohydrate diet is best for diabetic cats, unless contraindicated by other disease. Dietary management of renal disease using a restricted-protein diet should take precedence over dietary management of diabetes, and, in addition, acarbose should be used to reduce glucose absorption from the gastrointestinal tract.

Obesity in cats markedly reduces insulin sensitivity, and hence obese cats should be fed restricted energy so they lose 1–2% of bodyweight per week. Due to the decreased postprandial hyperglycaemia with a low-carbohydrate diet, it is suggested that diets with less than 20% of energy from carbohydrate should be used for obese diabetic cats during the calorie-restriction phase. Currently, most feline weight loss diets are low-fat, high-carbohydrate diets. Weight loss improves insulin sensitivity, and may reduce insulin requirements.

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.

Acarbose

The α-glucosidase inhibitors (e.g., acarbose) reduce intestinal glucose absorption and can be used in conjunction with insulin and/or other oral agents to gain better glycaemic control. Cats given acarbose and meal fed a high-carbohydrate diet have significantly reduced blood glucose concentrations, but the same effect can be achieved by using a low-carbohydrate diet. Acarbose is indicated as an adjunct to insulin therapy in cats which are meal fed a high-carbohydrate diet, e.g., obese cats. Cats in advanced renal failure requiring a protein-restricted diet usually have a reduced appetite and need to be fed ad libitum, which greatly reduces the efficacy of acarbose.

Oral Hypoglycaemic Drugs

Drugs which stimulate insulin secretion (e.g., sulphonylureas) require adequate beta cell function to be effective, and if there is inadequate glucose-lowering effect, persistent hyperglycaemia can lead to continued beta cell loss through glucose and lipid toxicity. These drugs may also stimulate accelerated islet amyloid deposition exacerbating beta cell loss. 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.

Insulin Therapy and Legislation

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. 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.

Insulin Therapy

Long-acting insulin therapy remains the preferred treatment for diabetes mellitus in cats. Its effectiveness and safety is enhanced when combined with a low-carbohydrate diet. Achieving good glycaemic control with intermediate-acting potent insulins such as NPH and lente is often difficult, and increases the risk of clinical hypoglycaemia. Recent data suggest that the long-acting insulins glargine and detemir provide better glycaemic control and reduced risk of clinical hypoglycaemia when given twice daily and combined with a low-carbohydrate diet. More importantly, their use results in a significantly higher probability for remission.

Cats presented with diabetic ketoacidosis can be treated with subcutaneous glargine during stabilisation. When used intramuscularly or intravenously, glargine acts like regular insulin and can be used for initial stabilisation in place of regular insulin.

Glargine

Glargine is a human synthetic insulin analogue. It differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the B-chain terminus. Glargine is a clear aqueous solution in 100 IU/ml vials and forms microprecipitates in the subcutaneous tissue providing relatively constant systemic absorption. Glargine cannot be mixed or diluted.

Glargine is marketed for human patients as a very long-acting 'peakless' insulin, with regard to its glucose-lowering effects. The expected benefits in diabetic cats of an insulin preparation with a longer duration of action include improved glycaemic control resulting in increased rates of diabetic remission.

In healthy cats once-daily administration of glargine has a similar mean daily glucose concentration and area under the 24-hour glucose curve to PZI, and both had significantly lower glucose concentrations over 24 hours than lente insulin. Glargine produced a glucose nadir later than PZI or lente, and had longer duration of action than lente. The duration of action for glargine was 22 hours, and five of nine cats had significantly decreased blood glucose concentration at 24 hours.

However, glargine has a longer effect if administered twice compared to once daily, and once-daily administration produces similar remission rates to twice-daily dosing of lente insulin. Twice-daily dosing is recommended as excellent glycaemic control facilitates remission, and superior glycaemic control is achieved if glargine is injected twice daily.

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. When evaluating the blood glucose curve using glargine, it is often more useful to assess pre-insulin glucose concentration rather than the nadir glucose. 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 newer synthetic insulin analogue with long duration of action. Detemir results in similar remission rates and time to remission as glargine, but the median maximum dose used (1.75 IU/cat q12h) is approximately 30% less than that of glargine (2.5 IU/cat q12h).

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 as shown in Figure 1. Cats treated with glargine should have a negative, 1+ or 2+ urine glucose (scale 0–4+); a value of 3+ or 4+ probably indicates that a dose increase is required. Owners should be encouraged to do home glucose monitoring to facilitate tight glycaemic control.

The good glycaemic control achieved when using glargine or detemir probably reverses glucose toxicity of b-cells, which facilitates endogenous insulin production and a reduced requirement for exogenous administration. Insulin dose may be reduced sequentially as indicated by blood glucose concentration, urine glucose and water intake, until the dose is 0.5–1 IU/cat q24h. Insulin may then be withdrawn, and the cat carefully monitored afterwards to ensure remission has continued. Even if normoglycaemic, it is recommended that insulin is not withdrawn within 2 weeks of commencement of therapy. 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, e.g., > 6 months, are less likely to go into remission, probably because of progressive beta cell loss associated with glucose toxicity.

In conclusion, although in many parts of Europe, porcine 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.

Figure 1. Dosing protocol for cats on glargine, detemir or PZI and glucose monitoring every 1–2 weeks.

Doses are per injection. Parameters are for changing insulin dosage when using insulin glargine, detemir or PZI in diabetic cats being assessed with serial blood glucose measurement every 3–4 hours over 12 hours once a week (preferred) or once every 2 weeks in the first 4 months of therapy. Blood glucose concentrations were based on using a portable glucose meter calibrated for human use which measures glucose concentration in whole blood. When using a meter calibrated for feline blood, target glucose concentrations at the lower limit of the range should be adjusted by adding approximately 1 mmol/l (18 mg/dl) to the value listed in the protocol. For example, a target value of 3 mmol/l (> 54 mg/ dl) becomes 4 mmo/l (> 72 mg/dl) when using a serum chemistry analyser or a meter calibrated for feline use or a serum chemistry analyser.

Monitoring Therapeutic Efficacy

Response to treatment can be evaluated using a combination of owner assessment, clinical signs and changes in bodyweight and water intake. The pre-insulin glucose concentration is important when using glargine, detemir and PZI, as there is often a persisting effect from the previous injection. Nadir (lowest) glucose concentration limits the dose increase that can be made when nadir glucose concentration is in the lower end of the normal reference range.

When using other insulins (e.g., lente or NPH), dosage changes are usually based on nadir blood glucose. Pre-insulin glucose, time to nadir and the time to return to baseline are also used where appropriate, and protocols are available at website www.uq.edu.au/ccah.