Richard W. Nelson, DVM, DACVIM
Establishing the Diagnosis
The diagnosis of diabetes mellitus in dogs and cats is based on three findings: appropriate clinical signs (polyuria, polydipsia, polyphagia, weight loss), persistent fasting hyperglycemia, and glycosuria. It is important to document both persistent hyperglycemia and glycosuria because hyperglycemia differentiates diabetes mellitus from primary renal glycosuria, and glycosuria differentiates diabetes mellitus from other causes of hyperglycemia, most notably epinephrine-induced stress hyperglycemia that may develop around the time of blood sampling.
A thorough evaluation of the patient's overall health is recommended once the diagnosis of diabetes mellitus has been established to identify disease that may be causing or contributing to the carbohydrate intolerance (e.g., hyperadrenocorticism), that may result from the diabetic state (e.g., bacterial cystitis), or that may mandate a modification of therapy (e.g., pancreatitis). The minimum laboratory evaluation should include a CBC, serum biochemistry panel, and urinalysis with bacterial culture. Serum progesterone concentration should be determined if diabetes mellitus is diagnosed in an intact bitch, regardless of her cycling history.
Treatment Options for Diabetic Dogs
Insulin is the cornerstone of therapy for diabetes mellitus in dogs. Insulin therapy should be started at the time diabetes is diagnosed. Diabetic dogs are reasonably predictable in their response to exogenous insulin. In my opinion, recombinant human or porcine lente insulin (Caninsulin®, Intervet Schering Plough) is the initial insulin of choice for treating newly diagnosed diabetic dogs. Recombinant human NPH insulin is also effective, but problems with short duration of effect are common with NPH insulin. Studies to date suggest that the median dosage of lente and NPH insulin required to attain glucose control in diabetic dogs is approximately 0.5 U/kg/injection, with a range of 0.2 to 1.0 U/kg. One important goal in the initial regulation of the diabetic dog is avoidance of symptomatic hypoglycemia, especially in the home environment. For this reason, my starting insulin dosage is always on the low end of the range (i.e., approximately 0.25 U/kg), and I prefer to start with twice-a-day insulin administration because the overwhelming majority of diabetic dogs require lente or NPH insulin twice a day.
My experience with insulin glargine (Lantus®, Sanofi-Aventis Pharmaceuticals) and recombinant human PZI insulin (ProZinc®, Boehringer Ingelheim Vetmedica) in diabetic dogs has been mixed and somewhat disappointing. My current insulin preference is insulin detemir (Levemir®, Novo Nordisk) in poorly controlled diabetic dogs where lente or NPH insulin is ineffective because of problems with short duration of insulin effect. The most common problem with insulin detemir is a prolonged duration of effect (greater than 14 hours), which can create issues with hypoglycemia when insulin detemir is given twice a day. Regardless, most diabetic dogs require insulin detemir twice a day to control the diabetic state, recognizing that the insulin dosage can be quite small to compensate for prolonged duration of effect in dogs with this problem. My initial starting dosage for insulin detemir in diabetic dogs is 0.1 to 0.2 U/kg.
Diet plays an important role in the successful management of the diabetic dog. The type of diet ultimately fed is dependent on the body condition of the dog (obese, optimum, or thin) and the presence and nature of concurrent disease (e.g., pancreatitis, kidney failure). Obesity should be corrected, if present. Obesity causes reversible insulin resistance, which resolves as obesity is corrected. Successful weight reduction requires a combination of restriction of caloric intake, feeding low calorie-dense diets, and increasing caloric expenditure through exercise. There are several diets specifically formulated for weight reduction in dogs; most contain fiber. In general, fiber-containing diets are indicated in obese diabetic dogs to help with weight reduction and are indicated in diabetic dogs at or near optimum body weight to help minimize post-prandial hyperglycemia. Viscous soluble fibers (e.g., gums, pectin) are more effective in slowing intestinal glucose absorption than insoluble fibers (e.g., peanut hulls, powdered cellulose). Diets containing a mixture of soluble and insoluble fibers are preferred for diabetic dogs. Maintenance diets containing small amounts of mixed fibers or minimal fiber are indicated in thin or emaciated diabetic dogs to promote weight gain. I recommend feeding low fat diets to diabetic dogs with a history of acute or chronic recurring pancreatitis or hyperlipidemia.
Exercise helps improve control of glycemia by promoting weight loss and by eliminating the insulin resistance induced by obesity. Exercise also has a glucose-lowering effect by increasing mobilization of insulin from its injection site, increasing blood flow (and therefore insulin delivery) to exercising muscles, and stimulating translocation (i.e., upregulation) of glucose transporters in muscle cells. The daily routine for diabetic dogs should include exercise, preferably at the same time each day. Ideally, exercise should occur at times of the day when the blood glucose concentration is likely to be high, not low (i.e., around the time of insulin injections, not around the time the glucose-lowering effect of insulin is peaking). I recommend clients exercise (usually walk) their diabetic dog twice a day around the time of each insulin injection. Strenuous and sporadic exercise should be avoided.
Treatment Options for Diabetic Cats
Although insulin is the cornerstone of therapy for diabetes mellitus, not all cats need insulin to control the diabetic state. The severity of pancreatic beta cell destruction is variable at the time diabetes is diagnosed in cats. Cats with severe loss of beta cells need insulin to control hyperglycemia. Cats with partial loss of beta cells and concurrent insulin resistance may or may not be insulin dependent. Adjustments in diet and correction of insulin resistance may correct hyperglycemia in some diabetic cats, while others initially require insulin to control hyperglycemia before undergoing diabetic remission. The decision to treat a newly diagnosed diabetic cat with insulin and diet versus diet alone is dependent on many factors, including the overall health of the cat, presence of ketosis or peripheral neuropathy, identification and ease of correction of insulin resistance, wishes of the owner, and intuition of the veterinarian.
Diet plays an integral role in the successful management of the diabetic cat. Correction of obesity is one of the cornerstones of dietary therapy. Obesity is especially common in diabetic cats and results from excessive caloric intake, typically caused by free-choice feeding of dry cat food. Improved sensitivity of tissues to insulin as obesity is corrected leads to improved control of the diabetic state. Diabetic cats may revert to a non-insulin-requiring diabetic state following weight reduction. Successful weight reduction in cats primarily relies on a combination of restriction of caloric intake and feeding low calorie-dense diets. In diabetic cats, I initially use diets containing high protein and low carbohydrate, unless kidney failure coexists. I consider switching to a high-protein, moderate carbohydrate, fiber-containing diet if palatability, worsening azotemia (if present), or inability to correct obesity become an issue with the high-protein, low-carbohydrate diet.
I prefer to initially use long-acting insulin preparations to treat diabetes in cats. Recombinant human PZI (ProZinc®, Boehringer Ingelheim Vetmedica) and the insulin analog insulin glargine (Lantus®, Sanofi-Aventis Pharmaceuticals) are recommended. Studies to date suggest that the median dosage of ProZinc and Glargine required to attain glucose control in diabetic cats is approximately 0.5 U/kg lean body weight/injection, with a range of 0.2 to 0.8 U/kg. One important goal in the initial regulation of the diabetic cat is avoidance of symptomatic hypoglycemia, especially in the home environment. For this reason, my starting insulin dosage is always at the low end of the range, which for most cats equates to 1 U per injection. I prefer to start with twice-a-day insulin administration when using ProZinc or Glargine because the majority of diabetic cats require these insulins twice a day to attain glycemic control.
Concurrent disease and medications, such as prednisone, cause insulin resistance and interfere with the effectiveness of insulin therapy in diabetic dogs and cats. The severity of insulin resistance varies from mild to severe depending on the underlying etiology. Excess glucocorticoids, growth hormone and progestagens cause severe insulin resistance and sustained and marked hyperglycemia regardless of the type or dose of insulin administered. In contrast, inflammation such as chronic pancreatitis and gingivitis, infection, obesity, hypothyroidism, and organ dysfunction such as kidney or heart failure cause insulin resistance, which is usually mild, often fluctuates in severity, and is relatively easily overcome by increasing the dosage of insulin. Disorders causing mild insulin resistance have a significant negative impact on control of the diabetic state, in part because of the fluctuating nature of the insulin resistance. Recognition and correction of insulin resistance, regardless of its severity, is critical for the successful management of the diabetic dog or cat. A thorough diagnostic evaluation of the newly diagnosed diabetic dog or cat is always indicated, including a CBC, serum biochemical panel, urinalysis with bacterial culture, serum T4 concentration, and serum progesterone concentration in an intact female dog, regardless of her cycling history. Acute and chronic pancreatitis is a common concurrent disorder in diabetic dogs and cats. Measurement of serum lipase immunoreactivity and performance of abdominal ultrasound to assess the pancreas should be considered.