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Diabetes Mellitus in Canines and Felines
Vol. No: 27:11 Posted: 11/15/02
Diabetes Mellitus in Canines and Felines
Elaine Lust, R.Ph., Pharm.D. candidate

 

Diabetes mellitus is a common endocrine disorder affecting canine and feline patients. Pharmacists working in a community or retail setting may be called upon to provide drug therapy and consulting services to the animal owner. With some specific education on this disease in animal patients, pharmacists should feel more confident in applying their drug knowledge resources to veterinary situations.

Canine Diabetes
Diabetes mellitus is defined as a condition in which a dog has a relative or absolute lack of insulin secretion by the beta cells of the islets of Langerhans in the pancreas. Diabetes mellitus is one of the most common endocrine diseases in canines, with peak occurrence in middle-aged and older dogs.1 A genetic predisposition to diabetes has been found in keeshonds and Samoyeds. Cairn terriers, poodles and dachshunds also have abnormally high rates of this disease.1 Obesity is a common factor in the development of diabetes in dogs and cats.1,2 TABLE 1 summarizes the similarities and differences of diabetes mellitus in canines versus felines.

In a diabetic dog the pancreas does not produce enough insulin, leading to high concentrations of glucose in the blood. Lack of glucose in the cells leads to catabolism of muscle and fat. Ketones are a byproduct of fat metabolism.1 Diabetic ketoacidosis is a serious complication of undiagnosed and untreated diabetes in canines, and requires the emergent care of a veterinarian.1,3

Classifications of diabetes as type 1, insulin-dependent diabetes mellitus (IDDM) or type 2, non-insulin-dependent diabetes mellitus (NIDDM) diabetes is not as useful in veterinary medicine as it is in human medicine because nearly all dogs and most cats will require insulin irrespective of the etiology.1 Dogs who develop primary type 1 often suffer from a complete absence of insulin secretion from the pancreas, and usually require insulin from the time of diagnosis.1,3 Categorization of primary and secondary causes is more clinically useful in veterinary medicine. Primary etiology involves islet cell destruction, possibly due to autoimmune disease or chronic pancreatitis.1,4 Secondary causes are obesity and antagonism to insulin, possibly due to hypothyroidism, hyperthyroidism, hyperadrenocorticism, or induction via glucocorticoids.1

 
Table 1: Similarities and Differences of
Diabetes Mellitus in Canines and Felines

Contributing Factors in Diabetes Mellitus

Felines

Canines

Common endocrine disorder

Yes Yes

Primary diabetes is most similar to human
Type II, NIDDM

Yes No
Primary diabetes is most similar to human
Type I, IDDM
No Yes
Peak occurrence in middle-aged to older animals No Yes
Breed predispositions No Yes
Initially presents as NIDDM and progresses
to IDDM
Yes No
Can experience transient diabetes Yes No
Obesity is a common factor Yes Yes
Higher incidence in males versus females Yes No

Feline Diabetes
Diabetes mellitus is a complex yet common endocrine disorder in cats. Diabetes mellitus can affect cats of any breed, sex, or age. However, risk factors for the development of diabetes include obesity, poor nutrition, and advancing age. Diabetic cats are generally overweight, with male cats showing a slightly higher incidence of diabetes than females.1,2,4,5

In felines, the most frequently diagnosed type of primary diabetes is similar to human type 2 non-insulin-dependent diabetes mellitus (NIIDM).4,5 There may be normal secretion of insulin, but the insulin does not appear effective in transporting glucose into the cells. Clinical signs of diabetes develop once the animal's normal insulin secretion decreases by 20% to 25%.5 Since some insulin is produced in type 2 diabetes, the disease state in not as severe, and diabetic ketoacidosis is not a common side effect.

Cats can slowly lose insulin secretion as beta cells are gradually destroyed.2 The patients have a period early in the disease where the type 2 hyperglycemia can be treated with oral hypoglycemics; however, over time, insulin secretion is lost and IDDM develops. Felines in particular, can initially present as having NIDDM, which eventually progresses to IDDM, or fluctuates between IDDM and NIDDM depending on the functioning level of the pancreatic beta cells.2

Type 1 feline patients have an absolute lack of insulin and are prone to developing diabetic ketoacidosis if insulin is withheld or if the diabetic condition is unrecognized and untreated. Diabetic ketoacidosis is considered a medical emergency. Immediate veterinary care is necessary to correct any electrolyte imbalances and reduce the level of ketone bodies present in the blood. According to Lutz, "Except for the fact that insulin dependence and ketosis are more frequent, feline diabetes has many of the same characteristics of the human disease. In both cats and humans, beta cell function is impaired and insulin secretion in response to a glucose load is abnormal."5

Up to 20% of felines can experience a transient diabetes mellitus, which is very rare in canines.2 Transient diabetes occurs when a diabetic cat spontaneously reverts to normal glycemic levels after being treated with oral hypoglycemic agents or insulin therapy. The Textbook of Veterinary Internal Medicine describes transient diabetes as a condition in which some diabetic cats "may never require insulin therapy once an initial period of insulin-requiring diabetes has dissipated, where as others become permanently insulin-dependent weeks to months after resolution of a prior diabetic state."2 The mechanism for this response is not well known, but some suggest that glucose toxicity is involved in the pathogenesis.2,5

Signs and Symptoms
Many of the clinical signs and symptoms of diabetes mellitus in canines and felines are the same as those seen in humans. Polyuria, polydipsia, polyphagia, and weight loss are hallmark signs of diabetes mellitus in cats and dogs. The onset of these signs and symptoms is insidious and can occur over weeks to months.1-3 When the blood glucose level is significantly elevated, the kidneys can no longer handle the workload and therefore allow the excess glucose to spill over into the urine. This glucose in the urine acts osmotically to draw more water into the urine, resulting in polyuria (excessive urine production). The animal compensates for this extra fluid loss by increasing water consumption (polydipsia). Owners will report to the veterinarian that the animal is urinating frequently in the home, or there is a constant need to change the cat's litter box.2 Other signs of diabetes that an owner or veterinarian can look for include polyphagia (increased appetite), and weight loss due to the breakdown of fat and muscle. Recurrent urinary tract infections (UTIs) are common in both species, and cataract development in canines may be noted on clinical examination.

Cataract development is something that is unique to dogs. Cataract development is a common and serious long-term complication of diabetes mellitus in canines. The lens of a dog's eye allows sugars (glucose and sorbitol) to enter, leading to fluid accumulation that causes an irreversible disruption of lens fibers. This results in lens opacity and cataract development. Some dogs can progress from having normal vision to near total blindness over a period of days to months.2 This may be one of the first signs of hyperglycemia noted by the owner and is the main reason a diabetic dog is taken to the veterinarian for care (FIGURE 1). The lens of the cat does not have this property.

Felines in the early stages of diabetes mellitus remain active and alert, with few signs of disease. However, as the disease progresses, cats will stop grooming, and poor skin and hair-coat conditions become evident.2 Secondary bacterial infections such as urinary tract infection (UTI) become more common. While cats can demonstrate many long-term complications, neurologic problems are the most identifiable.1,2 Diabetic neuropathy will cause cats to become progressively weaker in the rear legs and they assume a unique posture termed "plantigrade stance" (FIGURE 2 and FIGURE 3). This stance is used to identify diabetic neuropathy in cats. The hindquarters lack muscular strength and the cat acts as though sitting down all the time. The cat will also drag his or her back legs when attempting to walk. This condition may occur as one of the early signs of diabetes in the feline patient, or it can occur later in the stage of the disease, especially if the cat is poorly regulated.

Diagnosis
 
Eighteen-year-old female poodle with cataract development. Photo copied with permission from Washington State University, College of Veterinary Medicine Image Database at http://imagedb.vetmed.wsu.edu.
A diagnosis of diabetes mellitus in a dog or cat is initially suspected if the four "classic" signs are present: polydypsia, polyuria, polyphagia, and weight loss. The animal's blood and urine will be tested for glucose. If glucose is detected in the urine, then it is definitely elevated in the blood. A diagnosis of diabetes should not be based on an elevated blood glucose determination unless a concomitant glycosuria is present.2

The normal range for blood glucose is 79-126 mg/dL for canines and 63-132 mg/dL in felines.6 Hyperglycemia is defined in either species as when plasma or serum glucose levels persistently exceed 200 mg/dL.4,7 Clinical signs indicative of hyperglycemia are uncommon until the plasma or serum glucose value remains consistently in excess of 180 mg/dL. While levels may transiently increase after a meal without disease, diabetes is the only condition that will allow the blood glucose level to exceed 400 mg/dL.

Blood sugar levels can be misleading in feline patients because a sick, stressed cat can have blood glucose levels as high as 300-400 mg/dL in the nondiabetic state.2,4,7 This epinephrine-induced, stress-related hyperglycemia can develop in felines at the time of blood sampling, resulting in falsely elevated glucose levels.2 This is unique to cats and has not been documented in dogs.2 Therefore, for a positive diagnosis of diabetes mellitus in felines, the urine must also be tested for glycosuria because this condition does not develop with stress hyperglycemia.

 
 
Diabetic feline assuming plantigrade stance. Photo copied with permission from Washington State University, College of Veterinary Medicine Image Database at http://imagedb.vetmed.wsu.edu.

 
 

Treatment Options for Canines
The mainstay of treatment for diabetic dogs is insulin. Regular insulin is used to correct hyperglycemia emergently in either species. The dog is usually hospitalized during initial treatment for diabetes mellitus so that the veterinarian can monitor the animal closely for the first two to three days to determine the most appropriate insulin dose. During a dog's hospital stay, a feeding schedule will also be determined to coincide with the insulin injections so that blood glucose levels can ideally stay within a treatment range of 100-200 mg/dL.4

NPH or Lente insulins are the insulins of choice for maintenance treatment of uncomplicated diabetes mellitus.2,4 The literature on insulin dosing frequently cites the need to administer insulin to dogs twice a day.1-4,6,7 Owners of diabetic dogs may take one to two weeks to establish a daily routine of insulin injections and feeding schedule. The following is a dosage recommendation schedule for NPH or Lente therapy in canines.1-3,6,7

NPH or Lente: Administer insulin SQ at 0.5-1 units/kg depending on the weight of the dog. Administration can be once or twice daily. However, most dogs will require twice daily injections for optimal control.1-3,6,7

It is not common practice to use oral hypoglycemics in dogs. Since nearly all dogs have lost the ability to produce insulin, oral hypoglycemics such as glyburide and glipizide are of no utility in the diabetic dog.1-3

Treatment Options for Felines
 
Feline receiving subcutaneous insulin injection. Image copied with permission from www.peteducation.com
Felines can receive the same insulin preparations available to humans, but regulation of blood glucose can be challenging due to their insulin kinetics.1,2,4,5,7 There are many variables to treating diabetes in cats that make finding the initial insulin dose difficult. Diabetic cats have certain peculiarities not seen in dogs that can affect their treatment. First, there is a marked effect of stress on glucose concentrations in cats.2,4,7 Additionally, a cat's response to insulin is much less predictable than a dog's. Cats appear to metabolize insulin more rapidly than dogs.1 Furthermore, the same type of insulin may be absorbed and metabolized differently from one cat to the next.8

Establishing an insulin dose for a diabetic cat entails choosing an insulin type, dose, and dosing interval and carefully making necessary adjustments for two to three days. The initial hospital regimen often requires change because the diabetic cat is then allowed to go home, stress drops and food intake increases. Both of these factors have a significant effect on blood glucose levels. Control is considered to be achieved when the clinical signs have resolved, the pet is healthy and interactive in the home, and body weight is stabilized. Ideally, blood glucose concentrations can range between 100 and 300 mg/dL throughout the day.8 FIGURE 4 shows the subcutaneous administration of insulin to a feline.

Protamine Zinc Insulin (PZI) is manufactured by Blue Ridge Pharmaceuticals (www.brpharma.com) 1-800-374-8006. PZI is a long-acting insulin that historically was the drug of choice for treatment of diabetes in cats.2,4,6,7 Originally manufactured by Eli Lilly Co., it was discontinued in the early 1990s. Subsequently, Blue Ridge Pharmaceuticals purchased the manufacturing rights and is now the only licensed manufacturer of this insulin product. It has been ruled a medically necessary veterinary product by the FDA.

In cats, PZI insulin will begin to lower blood glucose in one to three hours; it has peak effect in four to ten hours post injection. The duration of action is from 12-30 hours. Because of the variability in duration of action and unpredictable response in cats, some animals may require twice-daily injections for optimal control.2,6

PZI: Begin dosing insulin SQ at 0.5-1 unit/kg once or twice a day.1,7 The Veterinary Drug Handbook recommends 1-3 units SQ once daily when initiating treatment.6

Establishing control of blood sugar levels in cats can be troublesome due to slow absorption of Ultralente from the subcutaneous site of injection. Unfortunately, approximately 20% of diabetic cats have inconsistent absorption of recombinant human Ultralente that requires relatively high doses of 8 to 10 units per injection.2 Feline patients who experience problems with glycemic control on Ultralente, may be switched to NPH or Lente. Following is a dosage recommendation schedule for Ultralente therapy in cats.

Ultralente: Begin administering SQ at 1-2 units twice daily.2,6 Most cats metabolize insulin very quickly relative to humans or dogs; therefore, they will enjoy better health by receiving NPH and Lente insulin twice a day.1,2,4,6-8 The following is a dosage recommendation schedule for NPH or Lente therapy in cats.

NPH or Lente: Administer insulin SQ at 0.25- 0.5 units/kg/day and slowly increase the dose as needed.6 The Textbook of Veterinary Internal Medicine suggests 1-2 units twice a day.2 Duration of effect of Lente and NPH can be considerably shorter that 12 hours, resulting in continued clinical signs of diabetes.2,3

Cats receiving maintenance insulin once daily should be fed half the daily food requirements at the time of injection and the remaining half at the time of peak insulin activity. If receiving twice-daily insulin injections, cats should be fed half the daily ration at each administration.

Glipizide is considered the oral hypoglycemic therapy of choice in felines. For glipizide to be effective in the glycemic control of NIDDM (type 2) in felines, there must be some insulin-secreting activity by the beta cells of the pancreas. Healthy diabetic cats who have been stabilized after the initial diabetic episodes and are type 2, are candidates for oral hypoglycemic medications. Clinical response can range from excellent to partial to no response.2 The quantity of functioning beta cells may account for the variations in clinical responses.2 Currently, no consistent parameters have been elucidated that allow a veterinarian to determine which cats will respond favorably to glipizide therapy. Oral therapy may be problematic because of the difficulty in administering oral medications to cats. Following is a suggested dosing regimen for glipizide in cats.

Glipizide: Administer orally at 2.5 to 5 mg twice a day with meals.6 It can take three to four weeks before a clinical response is observed.7 Vomiting within one hour of administration is a common side effect.2,7 Dosages may need to be decreased if vomiting is frequent or severe.

The most common side effect to watch for in canines and felines receiving insulin injections is hypoglycemia. Symptoms include weakness, lethargy, shaking, ataxia, seizures, and in severe situations, coma. Mild cases of hypoglycemia can be offset by offering the animal food. Moderate symptoms can be treated with dextrose gel, corn syrup or honey. Corn syrup is a good antidote for more severe hypoglycemic episodes. If an animal appears to be hypoglycemic, 1 tsp corn syrup can be given orally or rubbed onto the oral membranes. TABLE 2 summarizes the current pharmacotherapy options for treatment of diabetes mellitus in canines and felines.

 
Table 2: Mellitus in Canines and Felines
  Canines Felines
Regular For emergency treatment
of ketoacidosis
For emergency treatment
of ketoacidosis
NPH 0.5-1 units/kg SQ depending on
the weight of the dog, usually BID
0.25-0.5 units/kg/day SQ
or 1-2 units BID
Lente 0.5-1 units/kg SQ depending on
the weight of the dog, usually BID
0.25-0.5 units/kg/day SQ
or 1-2 units BID
Ultralente Not commonly used

1-2 units SQ twice daily

PZI Not commonly used 0.5 -1 unit/kg SQ QD to BID,
or 1-3 units QD
Glipizide Not indicated 2.5 to 5 mg PO BID with meals

Prognosis
A favorable prognosis for diabetic canines and felines depends on several factors. Avoiding complications, the ability to control blood glucose levels, level of owner commitment, and negative effects of concurrent disease states all contribute to an animal's prognosis. Diabetes mellitus carries a guarded long-term prognosis.2 Age of the animal at the time of diagnosis, combined with underlying complications or concurrent disease states, are predictors of survival times. Death shortly after receiving a diagnosis of diabetes is usually due to severe ketoacidosis or concurrent disease states. Death weeks to months after diagnosis and therapy is commonly due to the inability to establish sufficient glycemic control.2 However, with proper care by animal owners and veterinarians, diabetic canines and felines can live relatively normal lives for several years.2

Additional Resources
The Lilly Diabetes Answer Center is a resource for pharmacists and veterinarians alike. Questions pertaining to insulin usage in companion animals can be directed to Elanco Animal Health (the animal health division of Eli Lilly) at 1-800-428-4441.

REFERENCES

1. Dunn, JK, ed., Textbook of Small Animal Medicine. Philadelphia: WB Saunders. 1999:561-567.

2. Ettinger SJ, Feldman EC. Textbook of Veterinary Internal Medicine. 5th edition. Philadelphia: WB Saunders. 2000:1438-1460.

3. Fleeman LM, Rand JS. Management of canine diabetes. Vet Clin of North Am: Small Animal Practice 2001;31(5):855-880.

4. Davidson, G. Providing care for diabetic veterinary patients. Int J of Pharm Compounding. 2000;4(5):386-389.

5. Lutz AT, Rand, JS. Pathogenesis of feline diabetes mellitus. Vet Clin of North Am: Small Animal Practice 1995;25(3):527-551.

6. Plumb, DC. Veterinary Drug Handbook. 4th edition. Iowa State University Press;. 1999:1-912.

7. Booth DM. Small Animal Clinical Pharmacology and Therapeutics. 1st edition. Philadelphia: WB Saunders. 2001:636-644.

8. Nelson, RW. Adjunct Therapy for Diabetes Mellitus in Dogs and Cats. Nebraska Veterinary Medical Association, Convention Proceedings. Lincoln, NE. January 15-17, 2001.

 
Vol. No: 27:11 Posted: 11/15/02
December 2006
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