Feline Diabetes Mellitus

Jacquie S. Rand, Queensland, Australia

Diabetes mellitus is the second most common endocrinopathy in cats and affects approximately 1 in 50 to 1 in 400, depending on the population studied. Risk factors include advanced age, male sex, breed, obesity, physical inactivity, confinement indoors, and administration of glucocorticoids or progestins. Breeds reported at risk are Burmese in Australia, New Zealand, and the United Kingdom and Maine coon, domestic longhair, Russian blue, and Siamese in the United States.

Diagnosis of diabetes mellitus is based on the finding of persistently increased blood glucose concentration. In most cats, diabetes is usually not diagnosed until relatively late in the disease process when extensive β-cell function has been lost. The diagnosis is typically made when blood glucose concentration is above the renal threshold (i.e., >250 to 290 mg/dl [14 to 16 mmol/L]) and signs of polyuria, polydipsia, and weight loss are apparent. In contrast, in humans with type 2 diabetes, diagnosis is made earlier in the disease process. Because of this difference in diagnosis and extent of β-cell failure, most humans but only the minority of cats can be managed satisfactorily with oral hypoglycemic drugs.

At the present time, there is no consensus in the veterinary literature regarding the minimal blood glucose concentration in cats that should be classed as diabetic. Based on data in other species, blood glucose concentrations below the renal threshold but persistently greater than normal are likely associated with adverse effects, such as glucotoxic damage to β cells. Persistently mild hyperglycemia (e.g., >117 mg/dl fasted or >145 mg/dl unfasted to <180 mg/dl [>6.5 mmol/L fasted or >8.0 mmol/L unfasted to <10 mmol/L]) could be considered in cats to represent impaired fasting glucose, a state between normal and diabetic, which in human patients is considered to be prediabetic. Research is urgently required to define the cut-point between impaired fasting glucose and diabetes in cats; persistent blood glucose concentrations of 180 mg/dl (10 mmol/L) or greater likely indicate diabetes. In human patients with diabetes, 50% are undiagnosed, and there are more patients with prediabetes than diabetes. This is likely also the case in cats.

With the current availability of low-carbohydrate feline diets, research is needed to determine the most appropriate blood glucose concentration for institution of dietary management. Logically, if there are no contraindications such as azotemia, cats should be changed to a low-carbohydrate, high-protein diet whenever a persistently increased blood glucose concentration is present (e.g., >144 mg/dl [8 mmol/L] unfasted), and the diet is fed to achieve an ideal body weight. Cats should be monitored on a regular basis (e.g., every 3 to 6 months).

Pathogenesis of Diabetes in Cats

To manage diabetic cats effectively, an understanding of the pathogenesis and main features of feline diabetes is required. In developed countries, most owned cats with diabetes likely have type 2 diabetes, which is characterized by a relative lack of insulin secretion and insulin resistance. Insulin resistance reduces the glucose-lowering effect of a given amount of insulin. Diabetic cats are on average six times less sensitive to insulin than healthy cats, representing a similar magnitude of insulin resistance to that identified in humans with type 2 diabetes. Insulin resistance results from numerous mechanisms, and more than one mechanism is likely operating in most diabetic cats. A small percentage of cats have other specific types of diabetes resulting from β-cell destruction associated with pancreatitis and neoplasia or have marked insulin resistance from excess growth hormone or corticosteroids. In referral practice, cats with other specific types of diabetes account for a substantial proportion of diabetic cats; acromegaly (growth hormone–producing tumor) has been reported in 25% to 30% of diabetic cats, and pancreatic neoplasia was reported in necropsy specimens of 8% to 18% of diabetic cats at referral institutions in the United States. Pancreatitis is likely an underdiagnosed cause of diabetes, and anecdotal data indicate it might be a cause of diabetes in cats that achieve remission as well as cats that remain dependent on insulin throughout their life. Hyperthyroidism results in glucose intolerance and insulin hypersecretion, both of which are exacerbated in some cats after treatment of hyperthyroidism and might be the result of weight gain and resultant obesity.

Management of Diabetes

The most important goals of therapy are to achieve diabetic remission in cats with newly diagnosed diabetes; resolve clinical signs; and avoid clinical hypoglycemia, which can be life-threatening. The best way to resolve clinical signs is to achieve diabetic remission. Treatments available for management of feline diabetes include dietary modification, insulin, and oral hypoglycemic drugs. The prevalence of diabetes is increasing as risk factors such as obesity and physical inactivity become more common. These risk factors also need to be addressed in management and prevention of diabetes. Maintaining ideal body weight and avoiding drugs such as corticosteroids and progestins are important for maintaining remission.

Diet is an important component of therapy, and a low-carbohydrate diet is vital for cats achieving diabetic remission because it decreases mean daily glucose concentration, an important contributor to recovery of β cells from glucose toxicity (see also Chapter 46). A high-carbohydrate diet (50% of energy from carbohydrate) can increase mean blood glucose concentrations 4 to 18 hours after eating by 20% to 25% and peak glucose concentrations by more than 30% compared with a moderate-carbohydrate diet (25% energy from carbohydrate); comparison with a low-carbohydrate diet is even more pronounced. Remission rates were significantly higher (68% versus 42%) in cats fed a low-carbohydrate diet (12% of energy from carbohydrate; 3.5 g/100 kcal ME) compared with cats fed a higher carbohydrate diet (26% of energy from carbohydrate; 7.6 g/100 kcal ME), despite similar protein content of the two diets. Cats eating an ultra-low-carbohydrate diet (5% of energy; 1.8 g/100 kcal ME) have even greater reduction in blood glucose concentration; however, no studies comparing remission rates in cats fed low-carbohydrate and ultra-low-carbohydrate diets have been published. Ultra-low-carbohydrate diets are often nearly all meat or fish, may not be complete or balanced, and are high in phosphorus, which is of concern given the frequency of chronic kidney disease in diabetic cats.

Reducing carbohydrate content of the diet also decreases the demand on β cells to secrete insulin. Cats in diabetic remission likely have reduced β-cell mass. From the limited testing reported, most of these cats have impaired glucose tolerance, and about one third have impaired fasting glucose, meaning a glucose concentration above normal (117 mg/dl [6.5 mmol/L]) but less than diabetic (180 mg/dl [10 mmol/L]). It is vital that cats in remission be fed diets that minimize the amount of insulin required to be secreted to control postprandial glycemia. Feeding a low-carbohydrate diet once diabetic remission is achieved would likely prolong remission.

To achieve and maintain remission, it is important to attain an ideal body weight because of the negative impact of obesity on insulin sensitivity. Diet is also important for achieving weight loss. A minority of cats fed canned low-carbohydrate, high-protein diets self-restrict energy intake and lose weight spontaneously after their diet is changed. For most cats, energy intake needs to be restricted to achieve weight loss. Physical activity promotes weight loss and improves insulin sensitivity in other species, independent of body weight. Encouraging owners to engage in active play with their cat is likely beneficial.