S. Daminet, DMV, PhD, DACVIM, DECVIM-ca
Department of Small Animal Medicine Faculty of Veterinary Medicine, Ghent University
Treatment of a diabetic pet can be a difficult experience for the owner, the veterinarian, and the animal itself. However, an understanding of the pathogenesis of diabetes and its particularities, a thorough approach and good communication with the owner should allow you to turn it into a positive experience in many cases. Several clinical cases will be discussed during this presentation.
Pathogenesis of diabetes mellitus (DM)
Autoimmune destruction of pancreatic β cells has been forwarded as the cause of type 1 DM (formerly called insulin-dependent DM). Some cats but almost all dogs suffer from this type of diabetes and always require an insulin treatment. The etiology of type 2 DM is less clear, and is characterized by an inadequate secretion and an altered action of insulin. Deposit of amyloid in the pancreatic islets is frequently observed in diabetic cats. Cats affected by type 2 DM (formerly called non-insulin dependent DM) also often require treatment with insulin. It is currently believed that the incidence of type 2 DM is slightly more frequent than type 1 in cats. It is important to mention that there is presently no reliable or practical test available to prospectively differentiate between the 2 types of DM. Type 3 DM, also called secondary DM, results from other diseases, hormonal influences or medications causing a decrease of insulin secretion or an altered action of insulin (pancreatic neoplasia, pancreatitis, cortisol, growth hormone, etc ...).
Glucose toxicity is an important point to consider especially in diabetic cats. It is defined as a decreased secretion of insulin by pancreatic β cells following a prolonged hyperglycemia. Initially, this inhibition is functional and reversible. However, structural changes ensue which become irreversible and lead to a diminished number of functional β cells. This phenomenon, also described in humans, has probably even more clinical implications in pets, since they are often presented when clinical signs are well established and a marked hyperglycemia is observed.
Transient DM: A study published in 1999 by RW Nelson et al., reported 10 cats (over 3 years) with transient diabetes. Resolution of DM seems to be closely related to a rigorous control of blood glucose and can be definitive or transitional and last a period of months or years. No findings (history, physical examination or clinicopathological) allowed prediction of which cat could eventually have a remission of his DM.
Establishment of the diagnosis
In non-complicated DM, frequently reported clinical signs are polyuria/polydipsia, polyphagia and weight loss. These signs can be marked or go unnoticed by the owners (outdoor cat for example). Anorexia, lethargy, vomiting, and diarrhea are more commonly observed in complicated DM (ketoacidosis). Occasionally a plantigrade stance may be observed in cats. Dogs can present with cataracts. Diagnosis is confirmed by observation of hyperglycemia associated with glucosuria. In some cases, diagnosis can be more difficult because of stress hyperglycemia, typically observed in cats. In stress hyperglycemia, the glycemia can sometimes be over 16 mmol/L and occasionally glucosuria is observed. When clinical signs are not typical, the diagnosis becomes more difficult to confirm. In these cases, repeated measurement of blood glucose, home monitoring of urine glucose or determination of fructosamine are all ways to resolve the problem. A complete blood count, biochemical analysis, and urinalysis are indicated to detect any concomitant disease and the possibility of a urinary tract infection.
Treatment of DM has several goals: to reestablish glycemia in order to eliminate clinical signs of polyuria/polydipsia and polyphagia, to prevent complications related to diabetes, and to avoid hypoglycemia. The repercussions of a persistent hyperglycemia are also important because they can lead directly to the destruction of pancreatic β cells, which worsens the DM (e.g., glucose toxicity). It is thus important to rapidly and aggressively treat DM. Besides an appropriate diet, 2 types of treatments are available in cats: insulin therapy and oral hypoglycemic agents. Treatment in dogs should always be based on insulin therapy. Ovariohysterectomy in intact bitches developing DM is recommended.
Diet-feeding schedule: it is important to prescribe an appropriate commercial diet, for each patient, either to favor weight loss in obese patients or to ensure weight gain in thin patients. In diabetics, palatability and acceptance of the diet are also essential. Semi-moist diets or diets containing simple carbohydrates are to be avoided. For owner's convenience we tend to (at least initially) administer insulin injections and meal at the same time (every 12 h). The feeding schedule is adjusted if needed in light of the results of the blood glucose curve. Pets (especially cats) that are used to 'nibble' or 'graze' should still be allowed to do so even when diabetic.
Depending upon its duration of action, insulin can be classified in 3 categories: short- (regular), intermediate-(lente, NPH, Caninsulin®) and long-acting (ultralente or PZI in the USA) preparations. Concentrations frequently available are 100 U/ml or 40 U/ml, thus it is very important to use the appropriate syringes. The more diluted insulin is convenient in cats and small dogs. Insulin preparations used in pets are produced by genetic engineering (recombinant human) or are of pork origin.
In cats: initial recommended dosage varies from 0.25 to 0.5 U/kg, i.e., 1 to 3 U per cat. (the message is ... start low!) If the owner's schedule allows it, I prefer to initiate treatment with 2 injections of an intermediate acting insulin at 12-hour intervals. Otherwise, I initiate treatment with ultralente once a day. However, the absorption of ultralente is often delayed or its duration of action insufficient to allow for a good control of the diabetes.
In dogs: initial recommended dosage is around 0.5 U/kg 2x/day with an intermediate insulin.
Once treatment is initiated, the patient is discharged with appropriate instructions, or hospitalized for 24 hours to monitor for any signs of hypoglycemia. Also, one or two blood glucose measurements at the anticipated peak of action of the intermediate insulin are performed (in hospital or at home through home blood glucose monitoring by the owner). It is unnecessary to perform a complete glucose curve at this time. Dosage of insulin is very often increased much to quickly by veterinarians. Usually we wait 1 week before performing a blood glucose curve and before making adjustments in insulin dosage. Client communication is paramount: they must be informed of the clinical signs of hypoglycemia (lethargy, trembling, seizures) and on how to store and administer the insulin. I also inform them that usually 3 to 4 visits at one-week intervals are usually required to obtain an adequate control of the diabetes. Home blood glucose monitoring has greatly facilitated/improved monitoring of diabetic pets in the last years.
Second generation sulfonyureas (glipizide/glyburide) cause the release of preformed insulin by pancreatic β cells and also increase peripheral utilization of insulin. For these medications to be effective, pancreatic β cells need to be functional (type 2 DM). It is important to remember that we do not have a test that can predict which cat suffers from type 2 DM and thus be a candidate to receive hypoglycemic agents. This is why clinical criteria are used to determine which cat could be a potential candidate. If the cat is generally well, weight loss is mild, is not ketoacidotic and does not have a peripheral polyneuropathy; hypoglycemic agents can be tried. Glipizide (2.5 mg 2x/day) or glyburide (2.5 mg 2x/day) are available in many countries.
Certain authors/studies mention success rates of 25 to 65 % following administration of glipizide to cats. Others state that their experience with glipizide therapy is disappointing, without disclosing numbers. Whatever the actual figures may be, it is important when prescribing glyburide/glipizide to selectively choose the candidate and to inform the owners that this treatment can sometimes be disappointing. The limited success rate observed with glyburide/glipizide justifies close monitoring of the patient to rapidly detect if control is insufficient. The danger of glucose toxicity in diabetic cats also emphasizes the need to obtain a rapid control of the disease, and, thus, not to hesitate to recommend treatment with insulin if the results obtained with glyburide/glipizide prove to be unsatisfactory.
Other hypoglycemic agents such as metformin, acarbose, troglitazone and vanadium are used in humans suffering from type 2 DM and have a very different mechanism of action then glipizide/glyburide. Metformin inhibits hepatic glucose synthesis; acarbose inhibits intestinal absorption of glucose; vanadium and troglitazone increase the sensitivity of insulin receptors. Troglitazone and vanadium have been used in few diabetic pets, experience with these medications is still limited and first results seem disappointing. Dosage for acarbose is 12.5-20 mg/meal in dogs and cats. A not uncommon side effect is diarrhea.
Monitoring of the diabetic dog and cat
Adequate follow up of diabetic patients is essential and will be discussed in the following presentation.
The presence of concurrent diseases is not uncommon in older diabetic pets and can complicate the treatment of DM. Examples include pancreatitis, adenocarcinoma of the pancreas, chronic renal insufficiency, hyperthyroidism, infections (urinary tract infections, pyoderma), and lipidosis.
Controlling DM in dogs and cats requires a good motivation from the veterinarian and the owner. A remission is possible in certain cases of feline DM or in intact bitches after ovariohysterectomy. Oral hypoglycemic agents can be effective in some feline cases, but a rigorous monitoring is essential to detect cats that do not respond adequately to this treatment. Almost all diabetic dogs and many cats require insulin therapy and often 2 daily injections are necessary to obtain adequate control.