AAHA Diabetes Management Guidelines for Dogs and Cats

Abstract

Diabetes mellitus (DM) is a treatable condition that requires a committed effort by veterinarian and client. This document provides current recommendations for the treatment of diabetes in dogs and cats. Treatment of DM is a combination of art and science, due in part to the many factors that affect the diabetic state and the animal’s response. Each animal needs individualized, frequent reassessment, and treatment may be modified based on response.In both dogs and cats, DM is caused by loss or dysfunction of pancreatic beta cells. In the dog, beta cell loss tends to be rapid and progressive, and it is usually due to immune-mediated destruction, vacuolar degeneration, or pancreatitis.1 Intact females may be transiently 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.2Risk factors for both dogs and cats include insulin resistance caused by obesity, other diseases (e.g., acromegaly in cats, hyperadrenocorticism in dogs), or medications (e.g., steroids, progestins). Genetics is a suspected risk factor, and certain breeds of dogs (Australian terriers, beagles, Samoyeds, keeshonden3) and cats (Burmese4) are more susceptible.Regardless of the underlying etiology, diabetic dogs and cats are hyperglycemic and glycosuric, which leads to the classic clinical signs of polyuria, polydipsia (PU/PD), polyphagia, and weight loss. Increased fat mobilization leads to hepatic lipidosis, hepatomegaly, hypercholesterolemia, hypertriglyceridemia, and increased catabolism. Eventually, hyperketonemia, ketonuria, and ketoacidosis develop and result in progressive compromise of the animal.In this document, the authors describe different approaches to the animal depending on the level of hyperglycemia and severity of the clinical signs. Animals with DM may be presented with a variety of signs that are dependent, in part, on the time interval between onset of hyperglycemia and the client seeking veterinary help; the severity of hyperglycemia; presence and severity of ketonemia; and the nature and severity of concurrent disease, such as pancreatitis. Clinical signs of PU/PD do not develop until the blood glucose (BG) concentration exceeds the renal tubular threshold for spillage of glucose into the urine. In dogs and cats, glycosuria typically develops when the BG concentration exceeds approximately 200 mg/dL and 250 mg/dL, respectively.Clinical signs of DM are not generally present in dogs and cats with persistent fasting BG concentrations above the reference range but below the concentration that results in glycosuria (i.e., BG between the reference upper limit to 200 mg/dL in dogs and between the reference upper limit to 250 mg/dL in cats). BG concentrations in these ranges may occur for several reasons, including stress hyperglycemia (in cats), presence of an insulin-resistant disorder (e.g., obesity, hyperadrenocorticism), in association with medication (e.g., glucocorticoids), or as part of the early stage of developing DM.Dogs and cats that are in the early stage of developing DM are classified as subclinical diabetics. Subclinical diabetics often appear healthy, have a stable weight, and are usually identified when routine laboratory work is performed for other reasons. A diagnosis of subclinical diabetes should only be made after stress hyperglycemia has been ruled out and hyperglycemia persists despite identification and correction of insulin-resistant disorders. Reassessing the BG at home or measuring serum fructosamine concentration may help differentiate between stress hyperglycemia and subclinical DM and help determine if further action is needed.Clinical DM is diagnosed on the basis of persistent glycosuria and persistent hyperglycemia (>200 mg/dL in the dog and >250 mg/dL in the cat). Documentation of an elevated serum fructosamine concentration may be necessary to confirm the diagnosis in cats.5Animals with clinical diabetes manifest PU/PD, polyphagia, and weight loss. Some animals present with systemic signs of illness due to diabetic ketoacidosis (DKA), such as anorexia, dehydration, and vomiting. Additional problems may include lethargy, weakness, poor body condition, cataracts (in dogs), and impaired jumping ability and abnormal gait (in cats).The initial evaluation of the diabetic dog and cat should:The physical examination of the diabetic dog or cat can be relatively normal or may reveal dehydration, weight loss, dull coat, cataracts, or abdominal pain (if concurrent pancreatitis is present). A sweet odor may be noted on the breath if the animal is ketotic. Some cats with long-standing hyperglycemia may have a plantigrade stance secondary to a peripheral neuropathy.Laboratory assessment should include the items in Table 1. Typical findings include a stress leukogram and increased glucose, cholesterol, and triglyceride concentrations.Dogs often show increased alkaline phosphatase and alanine aminotransferase activity. In the cat, the stress leukogram and increases in alkaline phosphatase are variable. Cats with increased liver enzymes may have concurrent liver disease or pancreatitis and should be evaluated further.6Dogs and cats with DKA may show very elevated BG concentrations, alterations in liver enzyme activity and electrolyte concentrations, azotemia, and decreased total carbon dioxide secondary to metabolic acidosis, osmotic diuresis, and dehydration.7,8The urinalysis will reveal the presence of glucose and may reveal the presence of protein, ketones, bacteria, and/or casts. A urine culture should always be performed in glycosuric animals, as infection is commonly present.If thyroid disease is suspected in a dog, it is best to perform thyroid testing after diabetes is stabilized because of the likelihood of euthyroid sick syndrome. All cats >7 years of age with weight loss and polyphagia should be tested for hyperthyroidism, as diabetes and hyperthyroidism cause similar clinical signs and can occur concurrently.The mainstay of treatment for clinical DM in both species is insulin, along with diet modification. However, insulin treatment is not indicated in dogs and cats with subclinical disease, unless hyperglycemia worsens and glycosuria is noted.Veterinarians use a variety of insulin products, but only two are presently approved by the Food and Drug Administration (FDA) for use in dogs and cats. One of these is a porcine lente product (porcine zinc insulin suspension) that is approved for both dogs and cats.9 If available, the authors’ recommendation is to use this product in dogs. The other FDA-approved insulin is a longer-acting product (human recombinant protamine zinc insulin [PZI]) and is currently approved for use in cats.10 For the majority of diabetic cats, insulin glargine (not veterinary approved) and PZI have appropriate duration of action.Although bovine PZI is available from compounding pharmacies, its use is not recommended because of concerns about production methods, diluents, sterility, and the consistency of insulin concentration between lots. In addition, bovine insulin causes antibody production in dogs, which may impact control of DM.11Cats with subclinical DM may attain euglycemia without the use of insulin. Begin management with diet change. Evaluate and manage body weight, identify and cease any existing diabetogenic drug therapy, and correct concurrent insulin-resistant disease. Perform a recheck examination with urine analysis and BG measurement every 2 weeks. If clinical DM occurs despite dietary intervention, initiate insulin therapy.In addition to diet therapy, insulin treatment is required for cats with clinical DM.The insulin preparations with the appropriate duration of action in most diabetic cats are glargine (U-100) or the veterinary- approved human protamine zinc insulin (PZI U-40).31This panel does not recommend the veterinary-approved porcine zinc (lente) insulin suspension as the initial treatment for the cat, because its duration of action is short and control of clinical signs is poor.32 This insulin should be reserved for cats in which other insulin choices have not yielded satisfactory results.Judicious dosing is recommended initially, given that diet change may alter food intake and impact the response to insulin. Likewise, with ongoing therapy and reversal of glucotoxicity, the pet’s response to insulin will improve with time.17 Use caution in increasing the insulin dose too soon. Increases should only be made once food intake has stabilized and only if clinical signs have not improved after 1 week of therapy.Most cats are well regulated on insulin at 0.5 U/kg q 12 hours, with a range of 0.2 to 0.8 U/kg.15,33 The panel recommends a starting dose of 0.25 U/kg q 12 hours, based on an estimate of the cat’s lean body weight. This equates to 1 U q 12 hours in an average cat. Even in a very large cat, the starting dose of insulin should not exceed 2 U per cat q 12 hours.Monitoring strategies may be influenced by persistence or resolution of clinical signs. The pressing concern for the newly diagnosed and treated cat is the development of hypoglycemia in individuals that may quickly go into remission. Cats on long-acting insulin may not show overt signs of hypoglycemia until the BG is dangerously low, so it is important to identify impending hypoglycemia by home glucose testing whenever possible.If BG monitoring is not possible, close attention and documenting changes in clinical signs are imperative. Likewise, urine glucose testing using glucose-detecting crystals in the litter can be helpful for detecting diabetic remission.17Evaluate and recommend an appropriate diet that will correct obesity, optimize body weight, and minimize postprandial hyperglycemia. Dogs with DM can do well with any diet that is complete and balanced, does not contain simple sugars, is fed at consistent times in consistent amounts, and is palatable for predictable and consistent intake.Dietary considerations include:Treatment of clinical DM in the dog always requires exogenous insulin therapy. The U-40 pork lente (porcine zinc insulin suspension) has been the first-choice recommendation for dogs. The duration of action is close to 12 hours in most dogs, and the amorphous component of the insulin helps to minimize postprandial hyperglycemia.38 However, according to the FDA, that product has recently had “problems with stability,” and while the manufacturer is “working with FDA on resolving this issue, supplies may be limited” (http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm188752.htm; accessed 4/14/2010). If it again becomes consistently available, it will remain a great option for dogs. In the meantime, diabetic dogs should be started on a different insulin.39When porcine zinc insulin is not available, U-100 human recombinant Neutral Protamine Hagedorn (NPH) insulin is a good initial alternative, although its duration of action is often <12 hours in many dogs.40As a third option, human PZI is likely to be a better choice for dogs than is insulin glargine. There are no studies showing effective use of either of these products in dogs, however, glargine would likely require concurrent use of a short-acting insulin due to its slow release from subcutaneous tissues.Always tailor the monitoring and treatment to the dog. See Client Education for links to how-to videos and information.BGCs are part of the long-term monitoring plan. Create a BGC when:Use results to measure the nadir and to calculate the average BG over a roughly 12-hour period (average equals sum of all measurements divided by number of measurements). The BGC is the optimal way to assess:Initial BG measurements are performed as described under Initial Treatment. This is the protocol for the BGC in established diabetic animals.If the BGC is performed at home, have client measure BG before insulin or food is given. In free-fed cats, measure BG before insulin is given.The “uncontrolled diabetic” is one with poor control of clinical signs. This may include hypo- and hyperglycemic pets, those with insulin resistance (decreased responsiveness to the insulin, defined by >1.5 U/kg per dose), or those with frequent changes (up or down) in insulin doses. Any dog or cat with persistent BG >300 mg/dL despite receiving >1.5 U/kg per dose should be reevaluated [Table 1], as insulin resistance or insulin overdosage causing the Somogyi response is likely.Give clients a realistic idea of the commitment involved, along with positive encouragement that it is possible to manage this disease. Provide access to trained veterinary support staff and helpful web links. Stress the importance of appropriate nutrition and weight management. Table 2 provides web resources for education of staff and clients. Inform clients about the following:Management of the diabetic animal requires commitment and excellent communication between veterinarian and client about the treatment, follow-up appointments, associated costs, and home care. Diabetes is a dynamic disease, and successful management requires frequent client education and communication with the veterinary team. With appropriate client commitment, monitoring, and a firm understanding of the variables that are within our control, DM can be well managed.Important differences exist between the development of canine and feline DM, and understanding these differences will help predict management success. The recommendations made in this manuscript are intended to guide medical decisions and treatment choices, with the recognition that within each animal, variations in response will exist and no two cases are alike. In difficult-to-manage cases, you may consider consulting with or referring to an internal medicine specialist.