Definition
Diabetes is a chronic condition in which a deficiency of the hormone insulin impairs the body's ability to metabolize sugars. An estimated 16 million people in the United States have diabetes, and it is the most common hormonal disorder found in dogs. Diabetes is also diagnosed in cats, cattle, and horses.
"Diabetes generally affects middle-aged to older dogs and cats of any breed," says Dr. Jennifer Brinson, a veterinarian specializing in internal medicine at the University of Illinois College of Veterinary Medicine Teaching Hospital at Urbana.

Diabetes Mellitus is a group of conditions in which there is a deficiency of the hormone insulin or an insensitivity to it. Insulin is produced in the islet cells of the pancreas and is normally responsible for controlling blood concentrations of the body's main fuel, glucose. In normal animals, insulin does this by preventing glucose production by the liver and ensuring that excess glucose derived from food which is not needed for energy is put into body stores.

Insulin is produced in specialized cells in the pancreas. Insulin facilitates the movement of glucose (sugars) into the cells of the body for use as fuel. There are two types of diabetes. The first and most often seen, called insulin dependent, occurs when the body does not produce enough insulin. In the second, called insulin independent, enough insulin is produced, but something interferes with the insulin's ability to transport glucose.

In a diabetic animal there is insufficient insulin to switch off glucose production by the liver or to efficiently store excess glucose derived from energy giving foods. This means that the blood concentration of glucose rises and eventually exceeds a level beyond which the kidneys let glucose leak into the urine. This loss of glucose in urine takes water with it by a process called osmosis and causes larger volumes of urine to be produced than normal. The excessive loss of water in urine is compensated for by thirstiness and increased water consumption. The principal clinical signs of an animal with diabetes mellitus are therefore polyuria (excessive urination) and polydipsia (excessive water consumption). In addition, diabetic animals tend to lose weight because they breakdown stores of fat and protein (muscle) to make glucose and ketones (an alternative fuel) in the liver. Other clinical signs diabetics may include: cataracts, polyphagia (increased appetite), exercise intolerance and recurrent infections. If the production of ketones by the liver is excessive a condition called ketoacidosis occurs which makes the animal very unwell.

"The most common signs of diabetes are an increase in thirst and an increase in urination," says Dr. Brinson. "This is caused by excess glucose in the urine, which leads to excess water being lost with the glucose in the urine. Your pet will then feel the need to replenish the lost water supply."

There are a number of other things to look for if you suspect your pet has diabetes.
Commonly, people report that their pet has sticky urine. Since glucose is a great growth
medium for bacteria, urinary tract infections are also common, recognized by the presence of blood in the urine. Pets will also have a voracious appetite because the cells of the body are screaming for nourishment. At the beginning stages of the disease, this may cause weight gain, but later it causes weight loss. Lethargy, cataracts, and a poor hair coat may also be seen with diabetes.

"The biggest danger of this disease if it is left untreated is ketosis," says Dr. Brinson. "This happens when there is so much excess glucose circulating that the body begins to break it down into toxic compounds called ketones. Signs of ketosis include vomiting, severe depression, a refusal to eat, lethargy, or coma. You also might notice a sweet odor to your pet's breath if they are ketotic."

Diabetes is diagnosed through analyses of the blood and urine. Excess glucose in the blood and excess glucose in the urine on a consistent basis indicates that your pet has diabetes.
Dr. Brinson notes that other diseases cause high blood glucose levels or high urine glucose levels but rarely both.

"Treatment for insulin-dependent diabetes depends on if the pet has ketosis or not," says Dr. Brinson. "A pet that has increased drinking and urinating but a good attitude and appetite will be given injectable insulin to replace the insulin the body is not producing. This insulin is the same type given to humans and is usually given once or twice daily. The pet will often be switched to a diet high in fiber as well. An animal that has ketosis is treated with a very short-acting insulin immediately by your veterinarian and may need other therapy to correct the acid imbalance related to the ketones. Once stabilized, the pet will be treated like a healthy diabetic patient."

Animals with non-insulin-dependent diabetes pose a different problem. These patients are generally cats that are overweight. The treatment is to switch them to a high-fiber diet and reduce their weight. If this action does not correct the condition, their diabetes will be difficult to manage.

One to two weeks following the first insulin treatment, your pet should be brought to a
veterinarian so glucose levels can be tested several times in the day to check the efficacy of the current dose of insulin. This will allow your veterinarian to select the most appropriate dose of insulin for your pet. It is important for you to monitor your pet carefully at home to see if the signs are improving. See your veterinarian for an adjustment in the insulin level if the signs are not improving. "Never change the dose of insulin without first visiting your veterinarian," says Dr. Brinson. "Having too low a glucose level can lead to depression and seizures and can be just as life-threatening as too much."

With proper insulin regulation, the prognosis for a diabetic animal is very good. These
animals can live long and healthy lives as our friends and companions.

Therapy
Oral hypoglycaemic
Oral hypoglycaemic are tablets used in the treatment of human diabetes mellitus which can lower blood glucose in some cases. In general, they are not useful for the treatment of diabetes mellitus in dogs but are some use in a small proportion of diabetic cats.

Insulin
Insulin is the treatment of choice for diabetes mellitus in animals. Insulin must be given by injection because it is a protein and would be digested in the intestine if it was given as a tablet. Insulin is available as pharmacological preparations for subcutaneous injection which have been formulated to slow its absorption and prolong its action. There are three types of prolonged duration insulin preparations: lente (mixed insulin zinc suspension), isophane (NPH) and protamine zinc insulin (PZI). Of these, protamine zinc insulin has the longest duration of action and lente and isophane insulins last long enough to be used on a once, or occasionally twice, daily basis in diabetic dogs.

There are prolonged duration insulin products available in Britain, most of Europe, Canada and Australia with licenses for treating dogs and cats (Caninsulin, Insuvet Lente and Insuvet PZI).

Insulin products have to be treated carefully. They must be thoroughly mixed prior to use and must not be frozen, heated or shaken vigorously.

Stabilization
Unfortunately, there is no standard dose for insulin which can be applied to all animals. Each diabetic animal has to have its dose tailored to its individual needs which is done over a stabilization period. After such a period, maintenance insulin doses should remain relatively constant. In order to achieve stable control of a diabetic animal's blood glucose by insulin, all the other factors which affect blood glucose concentration must be kept constant from day to day. These factors include the composition, volume and timing of meals and the amount of exercise the animal gets.

To keep diet constant from day to day it is best to use commercially produced rather than home made diets. Certain prescription or veterinary diets can be a useful adjunct to insulin therapy such as Waltham Canine High Fiber, Hill's w/d or r/d. These diets should be avoided in underweight diabetics which need Waltham Concentration Diet, Hill's p/d or i/d. If special diets are unavailable then standard canned pet foods are acceptable.

There are a number of different ways to stabilize a diabetic animal. Some dogs are managed well with once daily injections but some will require twice daily. Some will be stabilized using blood glucose measurements taken by the veterinarian and others might be stabilized using urine glucose results. In some cases, hospitalization is necessary and in others it is not.

After stabilization has started the veterinarian often finds it useful to create a serial blood glucose curve by repeated measurements of blood glucose regularly throughout the day. Such a curve can be used to decide if the dog needs twice daily injections of lente or a change to PZI insulin.

The insulin treatment of cats is similar to that of dogs but requires at least twice daily injections of lente insulin or sometimes even twice daily injection of PZI because cats metabolize insulin much more rapidly than dogs.

One disadvantage to relying solely on pre-injection urine or blood glucose results is a phenomenon known as Somogyi overswing or insulin induced hyperglycaemia (high blood sugar). This is when an excessive insulin dose lowers blood glucose too far and the body responds to this potentially life threatening situation by producing hormones which are antagonistic to the effects of insulin. The release of these hormones causes blood glucose to rise again, often to very high levels which can spill over into the urine and produce strong positive morning urine glucose results. If adequate care is not taken, these results can be misinterpreted by an insulin adjustment protocol as indicating a requirement for an increase in dose. Such an increase will, in fact, only make matters worse. The possibility of inducing Somogyi overswing can be reduced by measuring urine glucose 3 times a day or by relying on nadir (lowest point in the day) blood glucose results for making insulin dose adjustments.

Problem cases
Non-specific illness
Dogs which are off their food or need to be fasted as part of the management of vomiting or diarrhea need to continue to receive insulin, since withholding both food and insulin is likely to start the production of ketones and this will make the dog more unwell. Usually half of the dog's normal requirement will prevent ketoacidosis and will be safe.

High insulin requirements
There are a number of conditions which can be associated with insulin insensitivity and therefore high insulin requirement (greater than 2 I U/kg). One of these results from insulin antagonism by progesterone in bitches which have recently been in season or which have had treatment to prevent them having seasons. Another is that caused by high levels of cortisol in diabetic dogs which also have hyperadrenocorticism (Cushings disease) or which have had repeated long acting glucocorticoid (steroid) injections. The best tests for hyperadrenocorticism are the low dexamethasone suppression test or the ACTH stimulation test but the results of these sometimes need to be interpreted with caution in diabetic dogs. Insulin insensitivity also occurs in dogs with chronic infections or chronic kidney failure.

Somogyi overswing
See above. This can be associated with unusually high doses of insulin and continued clinical signs of polyuria and polydipsia, particularly in the evenings when blood glucose has been increased by the release of protective hormones.

Rapid insulin metabolism
In some dogs, even the prolonged duration insulins are used up very quickly and are no longer effective after 12 or 14 hours. This means that clinical signs will reappear in the second half of the day. This situation is best discovered by serial glucose analyses (12 - 24 hour blood glucose curve) and can be remedied by the use of twice daily injections or a longer acting preparation.

Hypoglycemia
In diabetic animals treated with insulin there is some risk that hypoglycemia may occur. It is rare for a dog or cat to die of this condition but it is possible and owners should be appropriately warned and trained by the veterinary team responsible for their pet's management. It is most likely to happen if the animal is accidentally over-dosed with insulin, over-exercised or fails to eat its morning meal. The first noticeable clinical sign is hunger followed by lethargy and sleepiness. If untreated, stumbling and staggering ensue followed progressively by twitching, convulsions, coma and death. If the animal is still conscious, treatment is by offering food, particularly glucose containing foods such as biscuits or chocolate. If it is unable to eat, then glucose must be administered by mouth or by intravenous injection. Dissolved glucose powder or syrup will be absorbed quickly through the mucosa if poured into the side of the mouth. It is not necessary for it to be swallowed. HYPOSTOP or GLUTOSE 45 are a 40% dextrose gels which are convenient to carry and easily administered orally. There are also 20 and 40% dextrose (a form of glucose) solutions available for the veterinarian to use in emergency treatment.

Ketoacidosis
Ketoacidotic animals are usually collapsed, dehydrated and smell of ketones (like nail varnish remover). These dogs require more intensive therapy than normal diabetic dogs and this should include intravenous fluid and special soluble insulin therapy. Often the treatment of diabetic ketoacidosis is an intensive care situation.