DIABETES MELLITUS IN CATS

VetSuite Veterinarians
Endocrinology & Metabolic Diseases

Diabetes mellitus (DM) is a chronic disorder of carbohydrate metabolism caused by a failure of the hormone insulin to control glucose metabolism. It is one of the most common endocrine diseases of cats. DM leads to an inability of the tissue to utilize glucose. Disease occurs from high blood glucose levels, inadequate delivery of glucose to the tissues and changes in the body metabolism.

DIAGNOSIS OF DIABETES MELLITUS

ETIOLOGY AND RISK FACTORS

• Causes
• There are two types of diabetes mellitus. Type I DM is caused by destruction of the islet cells in the pancreas that normally produce insulin. Type II DM is caused by unresponsiveness of the tissues to the action of insulin. In type II DM, there may be low, normal or even increased amounts of insulin, but the insulin is ineffective.
• Chronic pancreatitis or repeated bouts of pancreatitis can result in diabetes.
• Risk factors
• Age - DM usually affects middle aged to older animals.
• Breed/genetics - No known risk
• Sex - No known risk
• Geographic/environmental - No known risk
• Other medical disorders - Overweight cats are more likely to develop type II DM than normal weight cats.

HISTORY AND CLINICAL SIGNS

• Species affected - Most cats develop Type 2 DM; however, about 50 percent will be insulin dependent at the time of diagnosis.
• Presenting signs and historical problems - The most common clinical signs are polyuria and polydipsia. Weight loss often occurs despite a good appetite. Cats may begin to walk on the heels of their back feet. Diabetic ketoacidosis can result in depression, vomiting, anorexia, dehydration and collapse.

PHYSICAL EXAMINATION FINDINGS

• General
• Attitude - Mental status can range from normal to comatose.
• Body condition - It is common for diabetic pets to be overweight.
• Vital signs - Vital signs are generally normal unless there are severe electrolyte disturbances, in which case tachycardia, bradycardia, dyspnea, hypothermia or hyperthermia may be observed.
• Mucous membranes - The color is typically normal but may be icteric in cats with concurrent liver disease, such as hepatic lipidosis. If significant dehydration is present, refill time may be delayed.
• Hydration status - Depending on the severity of the diabetes, some pets may be dehydrated and require hospitalization with intravenous fluids.
• Head and neck - Unremarkable
• Eyes - Cataracts may be present. Cataract formation occurs because of the abnormal accumulation of sugars in the lens of the eye. Although treatment of DM will not reverse cataract formation, surgical therapies for cataracts are an option.
• Oral cavity - In cases of ketoacidosis, a strong fruity acetone odor may be present on the breath.
• Thorax (cardio-pulmonary) - Tachypnea may be present in cases of ketoacidosis.
• Abdomen (gastrointestinal/urinary) - Abdominal pain may be present in cases of concurrent pancreatitis.
• Reproductive system - Unremarkable
• Lymph nodes - Unremarkable
• Integumentary system - Decreased skin turgor is often present in severe cases. Cats may also appear unkempt.
• Urinary/renal - Large bladder from polyuria; nephromegaly from diabetic nephropathy.
• Neurologic examination - Diabetic neuropathy results from changes to the nerves and is particularly common in cats. Most often, cats appear to walk on the heels of the back feet. Profound weakness can be present in cats suffering from ketoacidosis.
• Musculoskeletal examination - Unremarkable

DIAGNOSTIC STUDIES

• Clinical laboratory tests
• CBC - The complete blood count (CBC) often reveals a leukocytosis since infections are a common complication of DM.
• Serum biochemical tests - Biochemical analysis of the blood will allow confirmation of elevated blood glucose (BG) concentrations. Elevated blood glucose is the hallmark of DM. Results of biochemical analysis may reveal complications of DM and can often reveal the presence of concurrent diseases as well.
  
  Blood glucose concentrations should be repeated to confirm the diagnosis. Stress, a recent meal or certain drugs may cause mild to moderate elevations in blood glucose in the absence of DM. Persistent elevations in blood glucose, particularly after a fast, often suggests DM.Other biochemical changes often found include:
  
  ↑ Alkaline phosphatase
  ↑ ALT
  ↑ Cholesterol
  ↓ pH
  ↑ BUN/creatinine/phosphorus
  ↓ Sodium
  ↑ or ↓ Potassium
• Urinalysis - Analysis of the urine will often reveal the presence of glucose or ketones, as well as a urinary tract infection. The presence of glycosuria is crucial in confirming the diagnosis of diabetes.
• Coagulation profile - This is often unremarkable but clotting test may be prolonged in cases of diabetes complicated with disseminated intravascular coagulation.
• Serology/immunologic tests
• In order to determine the blood glucose concentrations over a period of several days, glycosylated hemoglobin, the product of the cumulative effect of blood glucose on red blood cell hemoglobin, is measured.
• Serum fructosamine measurements are used in the same way as glycosylated hemoglobin measurements. Fructosamine, however, is the product of the effect of blood glucose on the blood protein albumin.
• Microbiology - Urine culture may reveal bacterial infection.
• Diagnostic imaging
• Radiographs (thoracic/abdominal) - Abdominal radiographs are often performed to rule out other causes of the clinical signs. In diabetes, radiographs are usually normal.
• Ultrasound (abdominal) - As with radiographs, an abdominal ultrasound is often performed to look for concurrent illness, such as pancreatic inflammation.
• Electrodiagnostics
• ECG - This test may reveal sinus tachycardia but is often normal.
• EMG/Nerve conduction - Unremarkable, except in cases of feline diabetic neuropathy.
• ERG - If cataract surgery is anticipated, an electroretinogram should be performed to be certain that vision will be restored once the cataract is removed.

DIAGNOSIS AND PROGNOSIS

• Differential diagnosis - The differential diagnosis of diabetes mellitus should include the following:
• Polyuria and polydipsia can be caused by renal failure, liver failure, hyperadrenocorticism, urinary tract infection, diabetes insipidus and hyperthyroidism.
• High blood glucose can occur as a result of stress in cats.
• Weight loss while having a good appetite can be observed with intestinal disease, digestive enzyme failure, kidney disease, excess thyroid hormone or cancers.
• Pancreatitis can cause anorexia, vomiting and weakness. Occasionally, severe, repeated bouts of pancreatitis can damage the organ and cause DM, but pancreatitis can also occur in animals that already have DM.
• Recommended tests - Initial recommended diagnostic tests include:
• Serum biochemical profile
• Urinalysis
• Repeated measurements of BG

Results of these tests have been discussed previously.

• Summary of diagnostic criteria
• Blood glucose consistently elevated
• Glucose and possibly ketones in the urine
• Identification of associated medical disorders
• Prognosis - Prognosis in diabetes mellitus depends on a number of variables as well as the underlying condition. Organ damage associated with diabetes results in a poorer long-term prognosis. In uncomplicated diabetes, the prognosis is good. In severe complicated ketoacidosis, the prognosis is guarded to poor.

TREATMENT OF DIABETES MELLITUS

TREATMENT PRINCIPLES

By the time of diagnosis, most cats are insulin dependent, and insulin injections are the mainstay of treatment. Most cats will eventually require once or twice daily injections of insulin. In 50-60 percent of cats with type II DM, hyperglycemia can be controlled through weight management, diet changes and/or oral hypoglycemic agents. The key to dietary control is to restrict carbohydrate consumption to less than 10 percent of the diet on a dry matter basis. This is most easily achieved through the use of canned diets, which contain 5-12 percent carbohydrate on a dry matter basis. Dry cat foods contain anywhere from 15-60 percent carbohydrate on a dry matter basis. Patients with uncomplicated diabetes are generally managed on an outpatient basis, but those experiencing complications such as diabetic ketoacidosis will require initial in-hospital stabilization.

INITIAL/HOSPITAL THERAPY

• Symptomatic therapy - Underlying disorders should be treated as identified. Intravenous fluids are important in correcting underlying electrolyte disturbances and dehydration in complicated diabetes. The fluid of choice is 0.9% saline supplemented with potassium.
• Specific therapy - Insulin is the mainstay of treatment. For uncomplicated diabetics, cats are often started on NPH or lente dosed at 0.2 to 0.5 units per kg twice daily. Cats can also be given ultralente and PZI at 1 to 3 units per cat every 12 to 24 hours.
  
  Hypoglycemic agents can be used in cats. Glipizide is the most commonly used drug and is dosed at 2.5 to 5 mg per cat every 8 to 12 hours. A low carbohydrate diet is necessary when using oral hypoglycemic agents.
  
  In complicated diabetics, more aggressive treatment is necessary. After starting intravenous fluids, insulin treatment is initiated. There are two primary methods of treatment - intravenous insulin and intramuscular insulin. Regular insulin is used until the pet is stabilized.
• Intramuscular treatment
  If the blood glucose is over 250, administer an initial dose of 0.2 units/kg regular insulin IM. One hour later, recheck the BG and administer 0.1 units/kg IM. Continue to administer insulin at the 0.1 units/kg IM dose every hour until the BG is under 250. Check the BG every 1 to 2 hours.
  
  Once the BG is under 250, supplement the intravenous fluids with dextrose to make a 2.5% dextrose solution. Administer 0.1 to 0.4 units/kg regular insulin SQ. Recheck the BG every 6 to 8 hours. Once urine ketones are gone, discontinue the dextrose-containing intravenous fluids. Continue to monitor the BG. When the BG is in normal range, urine ketones are not present and the pet is clinically improved, transition to long-term insulin therapy.
• Intravenous treatment
  To begin, add 1.1 units/kg regular insulin to 250 mls of 0.9% saline. Allow about 50 mls to run through the plastic tubing before using the fluid. This fluid mixture should be given to the pet in a separate catheter from other fluids.
  
  If the BG is over 250, begin administering the insulin/fluid mixture at 10 ml/hr. Recheck the BG every 1 to 2 hours. Once the BG is between 200 to 250, add supplemental dextrose to the primary fluids to make a 2.5% solution. Reduce the insulin infusion to 7 ml/hr. Once the BG is under 200 mg/dl, reduce the insulin infusion rate to 5 ml/hr. When the BG reaches 100 or below, discontinue the infusion and begin administering 0.1 unit/kg regular insulin SQ every 4 hours. At this point, the BG can be checked every 4 hours. Once urine ketones are gone, discontinue the dextrose-containing intravenous fluids. Continue to monitor the BG. When the BG is in normal range, urine ketones are not present and the pet is clinically improved, transition to long-term insulin therapy.
  
  Antibiotics are often necessary to treat concurrent urinary tract infections.

LONG-TERM/HOME THERAPY

Long-term therapy also involves insulin administration. Some cats can be treated initially with a hypoglycemic agent. Unfortunately, most cats eventually become resistant and require injectable insulin therapy. The goal of long-term therapy is control of the diabetes through diet and medications.

Proper weight management aids in control of DM. Obesity causes tissues to be resistant to the effects of insulin, while animals that are too thin do not have any energy reserves. Maintaining an optimum weight can help both type I and type II diabetics.

A restricted carbohydrate diet and regular exercise can aid in control of DM. This can be achieved either by adding fiber to a canned formulation or by feeding foods restricted in carbohydrate, such as canned kitten formulations or those specifically designed for diabetic cats. Fiber slows the absorption of carbohydrates, and exercise helps improve the utilization of insulin by the tissues. Restriction of carbohydrate requires replacement of carbohydrate in the formulation with fat. Most canned formulations that are low in carbohydrate are replete in fat and protein.

Blood glucose curves are difficult to perform in cats; therefore, fructosamine is the preferred monitoring technique. Serum fructosamine will decrease to < 400 micromol/L in well-regulated diabetic cats.

Ovariohysterectomy is indicated in female diabetic animals since the hormonal changes in estrus alter insulin and glucose metabolism.

Antibiotics may be prescribed to treat infectious complications, particularly urinary tract infections or oral infections. Certain drugs, including steroids often used to treat skin conditions, should be avoided in diabetic pets.

Other drugs should be avoided when possible, including megestrol acetate (Ovaban®). Dietary supplements such as vanadium and chromium are gaining in popularity. No well-controlled studies support their use at this time, but in the future they might find a place in the treatment of DM.

FOLLOW-UP CARE

DM requires dedicated follow-up care on the part of the owner. With a commitment of time, education and careful observation on the part of the owner, most diabetic pets can live a good quality life.

It is recommended that insulin be given at a similar time each day. Proper client training and education is crucial. Insulin must be handled correctly and administered properly.

At home monitoring is also very important. Water consumption and urinary habits should be noted. Increases in thirst or frequency of urination may indicate the need for adjustment in insulin therapy or that a complication, like a urinary tract infection, has developed. Vomiting or anorexia should be treated.

Insulin should not be given if the pet is vomiting or has a poor appetite until the cause of the illness can be determined.

Home monitoring varies from veterinarian to veterinarian. Some rely on urine glucose tests and others prefer blood glucose tests to determine if the insulin dose and frequency is adequate. Many veterinarians now rely on clinical signs, primarily PU/PD, to determine if minor adjusts in the insulin dose are warranted.

NOTE: A well-regulated diabetic pet should look and behave the same as a pet in good health.