Companion Animal Diabetes Mellitus

Diabetes mellitus (DM) is a treatable condition that requires a committed effort by veterinarian and client. Due to many factors that affect the diabetic state, a pet’s changing condition, and variable response to therapy, management of DM is often complicated. Success requires understanding of current scientific evidence and sound clinical judgment. Each patient requires an individualized treatment plan, frequent reassessment, and modification of that plan based on the patient’s response. This document provides current recommendations for the diagnosis, treatment, and management of DM in dogs and cats.

Diabetes mellitus is a syndrome associated with protracted hyperglycemia due to loss or dysfunction of insulin secretion by pancreatic beta cells, diminished insulin sensitivity in tissues, or both. In the dog, beta-cell loss tends to be rapid and progressive, and is usually due to immune-mediated destruction, vacuolar degeneration, or pancreatitis. Intact female dogs may be transiently or permanently diabetic due to the insulin-resistant effects of the diestrus phase. In the cat, loss or dysfunction of beta cells is the result of insulin resistance, islet amyloidosis, or chronic lymphoplasmacytic pancreatitis.Studies have shown that diabetic cats have remission rates that have been reported to be variable (15–100%). Because remission can occur, cat owners may be advised that remission is a possibility when treated with combination of diet and insulin.

Risk factors for developing DM for both dogs and cats include insulin resistance caused by obesity, certain diseases (e.g., acromegaly and kidney disease in cats; hyperadrenocorticism [HAC], hypertriglyceridemia, and hypothyroidism in dogs; dental disease, systemic infection, pancreatitis, and pregnancy/diestrus in both dogs and cats), or medications (e.g., steroids, progestins, cyclosporine). Genetics is a suspected risk factor, and certain breeds of dogs (Australian terriers, beagles, Samoyeds, keeshonden) and cats (Burmese, especially in Australia and Europe) are more susceptible.Researchers continue to redefine and reclassify the different etiologies responsible for the development of DM in dogs and cats. As different etiologies become better understood, treatment can be more specifically tailored to the individual patient. Treatment that is more specific to the underlying etiology will presumably lead to better control of clinical signs of DM and possibly increase remission rates.

Regardless of the underlying etiology, classic clinical signs of polyuria (PU), polydipsia (PD), polyphagia (PP), and weight loss result from protracted hyperglycemia and glucosuria. Increased fat mobilization leads to hepatic lipidosis, hepatomegaly, hypercholesterolemia, hypertriglyceridemia, and increased catabolism. Eventually, if left untreated or inadequately controlled, ketonemia, ketonuria, and ketoacidosis develop and result in progressive compromise of the patient’s health.

Complications resulting from diabetes or its treatment are common in diabetic dogs and cats and include blindness and anterior uveitis resulting from cataract formation (dogs), peripheral neuropathy of the hind limbs, causing weakness, inability to jump, a plantigrade stance and ataxia (cats), chronic pancreatitis, recurring infections, hypoglycemia and ketoacidosis. Most of the devastating chronic complications of human diabetes (e.g., nephropathy, vasculopathy, and coronary artery disease) require 10 to 20 years or longer to develop and therefore are uncommon in diabetic dogs and cats. Diabetes mellitus is a disease of older dogs and cats, and most do not live beyond 5 years from the time of diagnosis.

The mean survival time for diabetic dogs and cats is approximately 3 years from the time of diagnosis, although survival time is somewhat skewed because dogs and cats are usually 7 years or older at the time of diagnosis, and the mortality rate during the first 6 months is relatively high because of concurrent life-threatening or uncontrollable disease (e.g., ketoacidosis, acute pancreatitis, renal failure). Diabetic dogs and cats that survive the first 6 months can easily maintain a good quality of life for longer than 5 years with proper care by the owners, timely evaluations by the veterinarian, and good client-veterinarian communication.

Treatment Plan

Treatment of clinical DM in the dog always requires exogenous insulin therapy. U-40 pork lente (porcine insulin zinc suspension; Vetsulin) is the Task Force’s first-choice recommendation for dogs using a starting dose of 0.25 U/kg q 12 hr, rounded to the nearest whole U. The duration of action is close to 12 hr in most dogs, and the amorphous component of the insulin helps to minimize post-prandial hyperglycemia. As with cats, a clinically sick, diabetic, ketotic dog should be admitted for 24 hr care for aggressive therapy of the ketosis and other underlying illnesses. A critical initial goal of treatment is avoidance of symptomatic hypoglycemia, which may occur if the insulin dose is increased too aggressively. Feed equal- sized meals twice daily at the time of each insulin injection. In contrast to cats, diabetic remission occurs only rarely in dogs with naturally acquired DM. Performing an ovariohysterectomy in intact diabetic dogs will support remission, regardless of the underlying cause of the diabetes.

In dogs with subclinical DM, investigate and address causes of insulin resistance, including obesity, medications, hyperadrenocorticism and diestrus in intact females. Initiate dietary therapy to limit postprandial hyperglycemia. Evaluate the dog closely for progression to clinical DM. Subclinical DM is not commonly identified in the dog. Most dogs in the early stages of naturally acquired diabetes (i.e., not induced by insulin resistance) quickly progress to clinical DM and should be managed using insulin.

Veterinarians use a variety of insulin products, but only two are presently approved by the FDA for use in dogs and cats. One of these is a porcine lente product (porcine insulin zinc suspension, Vetsulin) that is approved for both species. The other FDA-approved insulin, human recombinant protamine zinc insulin or PZI (Prozinc) insulin, is labeled as having an appropriate duration in cats, the only species for which it is approved. It is considered by clinicians as a long-acting insulin. Because of limited controlled comparative studies, most expert recommendations are based on a combination of clinical and anecdotal experience. The guidelines Task Force strives to make evidence-based recommendations when data are available. However, the ability to make specific recommendations based on differences and preferences between veterinary insulin products is limited. Members of the Task Force most commonly use porcine lente insulin (Vetsulin) in dogs and glargine (Lantus) in cats, recognizing that other acceptable options used by many clinicians include Neutral Protamine Hagedorn (NPH; Humulin N, Novulin N) in dogs and PZI (Prozinc) in cats.

Although compounded insulin is available, its use is not recommended because of concerns about production methods, diluents, sterility, and insulin concentration consistency between lots. A study comparing commercially available insulin with its compounded counterparts showed that the manufactured insulin met all US Pharmacopeia requirements and only 1 of 12 compounders met US Pharmacopeia specifications at all time points. The variability between compounded insulins was also significant enough to have clinical consequences. It is also not recommended to dilute insulin because dilution can produce unpredictable results, alter insulin efficacy, and result in bacterial contamination

Dietary Therapy Goals and Management

The goals of dietary therapy are to optimize body weight with appropriate protein and carbohydrate levels, fat restriction, and calorie and portion control. Weight loss in obese patients and stopping DM- ]associated weight loss are treatment goals for diabetic canine and feline patients. Dogs, unlike cats are not at appreciable risk for the clinical complications of hepatic lipidosis. Dogs with DM can do well with any diet that is complete and balanced, is fed at consistent times in consistent amounts, and is palatable in order to achieve predictable and consistent intake. For dogs, diets that contain increased quantities of soluble and insoluble fiber or that are designed for weight maintenance in diabetics or for weight loss in obese diabetics can: Improve glycemic control by reducing postprandial hyperglycemia. Restrict caloric intake in obese dogs undergoing weight reduction. Some clinicians recommend that owners supplement with canned pumpkin, green beans, or commercial fiber supplements containing psyllium or wheat dextrin. Additionally, regular and appropriate exercise should be considered an adjunct of any diet- based weight-loss program. In underweight dogs, the principal goal of dietary therapy is to normalize body weight, increase muscle mass, and stabilize metabolism and insulin requirements. Underweight dogs should be fed a high-quality maintenance diet or a diabetic diet that has both soluble and insoluble fiber and is not designed for weight loss. The diet should be palatable in order to provide predictable caloric intake when fed at consistent times and in consistent amounts. Owners should include treats when calculating daily caloric intake.

Dietary recommendations for both dogs and cats should be adjusted if concurrent diseases are present (e.g., chronic kidney disease, pancreatitis, intestinal disease). For dogs, a diet that will correct obesity, optimize body weight, and minimize postprandial hyperglycemia is recommended.

Monitoring

The overarching goal of monitoring diabetic cats and dogs is to control clinical signs of DM while avoiding hypoglycemia. Stated another way, the definition of a controlled diabetic is absence of clinical signs and hypoglycemia. Blood glucose levels do fluctuate and short periods of mild hyperglycemia are acceptable. The goal is not necessarily to normalize BG, but to keep the BG below the renal threshold (200 mg/dL in dogs and 250–300 mg/dL in cats) and to avoid hypoglycemia. When BG is above the renal threshold, glucosuria occurs, resulting in PU/PD. None of the monitoring modalities are perfect, and they each have strengths and weaknesses. Although normalizing clinical signs (such as resolution of increased urination, increase thirst, increased appetite, and achieving ideal body weight) supersedes all other monitoring. Monitoring diabetic pets can be challenging.Monitoring options include performance of BGCs, monitoring UG, measuring fructosamine, and assessment of clinical signs and weight. Results from different monitoring approaches may conflict. In a review of 53 cases of canine DM, BG measurements and fructosamine concentrations were consistent with good glycemic control in only 60% of dogs judged to have good clinical control. Furthermore, although all monitoring parameters were significantly improved in dogs with good clinical control, considerable overlap existed between dogs with good and poor clinical responses. In cats, no single monitoring parameter best correlates with the level of clinical control identified.

Home Monitoring

Observation of clinical signs is crucial to effective monitoring of DM. Owners should be encouraged to keep a daily log of appetite, observation of thirst (i.e., increased or normal), and insulin dose administered. Where DM monitoring is concerned, clinical signs supersedes all else. When the patient has minimal clinical signs and the body weight is steady or increasing, DM is likely well controlled. In cats, one of the parameters considered to be the most useful and practical indicator of clinical DM control is the amount of water consumed over 24 hr. Cat owners are often happy with the level of clinical DM control, despite not having laboratory evidence of tight glycemic control, emphasizing that the long- term goal of DM treatment is to normalize clinical signs. However, because a placebo effect can occur, judging the adequacy of DM control should not rely solely on owner observations.

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