Diabetes in cats

Diabetes mellitus is a chronic disease in cats, whereby either insufficient insulin response or insulin resistance lead to persistently high blood glucose concentrations. Diabetes could affect up to 1 in 230 cats,^[1] and may be becoming increasingly common. Diabetes mellitus is less common in cats than in dogs. 80-95% of diabetic cats experience something similar to type-2 diabetes, but are generally severely insulin-dependent by the time symptoms are diagnosed. The condition is treatable, and treated properly, the cat can experience a normal life expectancy. In type-2 cats, prompt effective treatment may lead to diabetic remission, in which the cat no longer needs injected insulin. Untreated, the condition leads to increasingly weak legs in cats, and eventually malnutrition, ketoacidosis and/or dehydration, and death.

Symptoms

Cats will generally show a gradual onset of the disease over a few weeks or months, and it may escape notice for even longer.

The first outward symptoms are a sudden weight loss (or occasionally gain), accompanied by excessive drinking and urination; for example, cats can appear to develop an obsession with water and lurk around faucets or water bowls. Appetite is suddenly either ravenous (up to three-times normal) or absent. These symptoms arise from the body being unable to use glucose as an energy source.

A fasting glucose blood test will normally be suggestive of diabetes at this point. The same home blood test monitors used in humans are used on cats, usually by obtaining blood from the ear edges or paw pads. As the disease progresses, ketone bodies will be present in the urine, which can be detected with the same urine strips as in humans.

In the final stages, the cat starts wasting and the body will breaking down its own fat and muscle to survive. Lethargy or limpness, and acetone-smelling breath are acute symptoms of ketoacidosis and/or dehydration and is a medical emergency.

Untreated, diabetes leads to coma and then death.

Diabetic emergencies

Too little insulin over time can cause tissue starvation (as glucose can't reach the brain or body). In combination with dehydration, fasting, infection, or other body stresses, this can turn over a few hours into diabetic ketoacidosis, a medical emergency with a high fatality rate, that cannot be treated at home. Many undiagnosed diabetic cats first come to the vet in this state, since they haven't been receiving insulin. Symptoms include lethargy, acetone or fruity smell on breath, shortness of breath, high blood sugar, huge thirst drive. Emergency care includes fluid therapy, insulin, management of presenting symptoms and 24-hour hospitalization.

Complications

The back legs may become weak and the gait may become stilted or wobbly, due to diabetic neuropathy, which is caused by damage to the myelin sheath of the peripheral nerves due to glucose toxicity and cell starvation, which are in turn caused by chronic hyperglycemia.^[2] Most common in cats, the back legs become weaker until the cat displays a plantigrade stance, standing on its hocks instead of on its toes as normal. The cat may also have trouble walking and jumping, and may need to sit down after a few steps. Some recommend a specific form of vitamin B₁₂ called methylcobalamin to heal the nerve damage. Neuropathy sometimes heals on its own within 6–10 weeks once blood sugar is regulated, but anecdotal evidence points to a faster and more complete recovery with methylcobalamin supplements.

Causes

The signs of diabetes mellitus are caused by a persistently high blood glucose concentration, which may be caused by either insufficient insulin, or by a lack of response to insulin.^[3] Most cats have a type of diabetes mellitus similar to human diabetes mellitus type 2, with β-cell dysfunction and insulin resistance.^[4] Factors which contribute to insulin resistance include obesity and endocrine diseases such as acromegaly.^[4] Acromegaly affects 20–30% of diabetic cats; it can be diagnosed by measuring the concentration of insulin-like growth factor-1 (IGF-1) in the blood.^[5]

Management

Diabetes can be treated but is life-threatening if left alone. Early diagnosis and treatment by a qualified veterinarian can help in preventing nerve damage, and, in rare cases, lead to remission.^[6] Cats do best with long-lasting insulin and low carbohydrate diets. Because diabetes is a disease of carbohydrate metabolism, a move to a primarily protein and fat diet reduces the occurrence of hyperglycemia.

Diet

Diet is a critical component of treatment, and is in many cases effective on its own. For example, a recent mini-study^[7] showed that many diabetic cats stopped needing insulin after changing to a low carbohydrate diet. The rationale is that a low-carbohydrate diet reduces the amount of insulin needed and keeps the variation in blood sugar low and easier to predict. Also, fats and proteins are metabolized slower than carbohydrates, reducing dangerous blood-sugar peaks right after meals.

Recent recommended diets are trending towards a low carbohydrate diet for cats^[8][9] rather than the formerly-recommended high-fiber diet. Carbohydrate levels are highest in dry cat foods made out of grains (even the expensive "prescription" types) so cats are better off with a canned diet that is protein and fat focused.^[10] Both prescription canned foods made for diabetic cats and regular brand foods are effective. Owners should aim to supply no more than 10% of the daily energy requirement of cats with carbohydrates.

Medications

Oral medications like Glipizide that stimulate the pancreas, promoting insulin release (or in some cases, reduce glucose production), are less and less used in cats,^[11] and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies^[12] to damage the pancreas further or to cause liver damage. Some owners are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor (most cats are easier to inject than to pill), and injections are more effective at treating the disease.

Insulin

The method usually employed is a dose of slow-acting insulin, twice daily, to keep the blood sugar within a recommended range for the entire day. With this method, it is important for the cat to avoid large meals or high-carbohydrate food. Meals may also be timed to coincide with peak insulin activity. Once-daily doses are not recommended,^[13] since insulin usually metabolizes faster in cats than in humans or dogs.^[14] For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat.^[15]

Cats may be treated with animal insulin (bovine-based insulin is most similar to cat insulin), or with human synthetic insulin. The best choice of insulin brand and type varies from animal-to-animal and may require some trial-and-error. The human synthetic insulin, Humulin N /Novolin N/ NPH, is usually a poor choice for cats,^[15] since cats metabolize insulin about twice as fast. The Lente and Ultralente versions were popular for feline use until summer 2005, when they were discontinued.

Until the early 1990s, the most recommended type for pets was bovine/porcine-derived PZI,^[16] but that type was phased out over the 1990s and is now difficult to find in many countries. There are sources in the US and UK, and many vets are now starting to recommend them again for pets, but they have been discontinued by most manufacturers as of 2007-2008. A new synthetic PZI analogue called ProZinc is now available.

Caninsulin (known in the USA as Vetsulin) is a brand of porcine-based insulin approved for cats which is available with a veterinarian's prescription. According to the manufacturer's website, the insulin's action profile in cats was similar to that of NPH insulin, and lowered blood sugar quickly, but for only about 6–8 hours. Vetsulin was recalled in the USA in November 2009 due to inconsistent strength; it was available again as of April 2013.^[17]

Two ultra-slow time-release synthetic human insulins became available in 2004 and 2005, generically known as insulin detemir (Levemir) and insulin glargine (Lantus). Studies have had good results with insulin glargine in cats.^[18] Follow-up research ^[19] shows that Levemir can be used with a similar protocol and that either insulin, on this protocol, can lead uncomplicated feline cases to remission, with the most success being in cats who start on these protocols as soon as possible after diagnosis.

Dosage and regulation

Cats may have their mealtimes strictly scheduled and planned to match with injection times, especially when on insulin with a pronounced peak action like Caninsulin/Vetsulin or Humulin N. If the cat free-feeds and normally eats little bits all day or night, it may be best to use a very slow-acting insulin to keep a constant level of blood glucose. Some veterinarians still use the outdated recommendation of using Humulin "N" or NPH insulin for cats, which is very fast-acting for most cats.^[13] The slower-acting Lente and Ultralente (Humulin L and Humulin U) insulins were discontinued in 2005) so most cats are treated with either the veterinary PZI insulins, or the new full-day analogs glargine (Lantus) and detemir (Levemir).

The first goal is to regulate the cat's blood glucose by keeping the blood glucose values in a comfortable range for the cat during the most of the day. This may take a few weeks to achieve.

The most successful documented method is tight regulation with Lantus or Levemir.^[20]

Typical obstacles to regulation include:

• Chronic overdose masked by Somogyi: A dose that is too high may cause a Somogyi rebound, which can look like a need for more insulin. This condition can continue for days or weeks.
• High-carbohydrate cat food: Many commercial foods (especially "light" foods) are very high in carbohydrates. The extra carbohydrates keep the cat's blood sugar high. In general, canned foods are lower in carbohydrates than dry foods, and canned "kitten" foods lower still. Diabetes in cats can be better regulated and even sometimes reversed with a low carbohydrate diet.^[21]
• Inappropriate insulin: Different brands and types of insulin have idiosyncratic effects on different cats. With some dosages, the insulin may not last long enough for the cat. Testing blood sugar more frequently can determine if the insulin is controlling the blood sugar concentration throughout the day.

Blood sugar guidelines

Taking a blood sample from a cat's ear to measure blood glucose concentration on a glucometer.

Absolute numbers vary between pets, and with meter calibrations. Glucometers made for humans are generally accurate using feline blood except when reading lower ranges of blood glucose (<80 mg/dl–4.44 mmol/L). At this point the size difference in human and animal red blood cells can create inaccurate readings.^[22]

Somogyi rebound

Too much insulin may result in a contradictory increase of blood glucose. This "Somogyi effect" is often noted by cat owners who monitor their cat's blood glucose at home. Anytime the blood glucose level drops too far to hypoglycemia, the body may defensively dump glucose (converted from glycogen in the liver), as well as hormones epinephrine and cortisol, into the bloodstream. The glycogen raises the blood glucose, while the other hormones may make the cat insulin-resistant for a time. If the body has no glycogen reserves, there will be no rebound effect and the cat will just be hypoglycemic. ^[23]

Even a small overdose can trigger a rebound effect (A typical case is increasing bidaily dosage from 1 unit to 2, passing a correct dose of 1.5 units.)

Rebound hyperglycemia occurs rarely in cats treated with glargine in a protocol aiming for tight control of blood glucose concentrations.^[24]

Hypoglycemia

An acute hypoglycemic episode (very low blood sugar) can happen to even careful pet owners, since cats' insulin requirements sometimes change without warning. The symptoms include depression/lethargy, confusion/dizziness, loss of excretory/bladder control, vomiting, and then loss of consciousness and/or seizures. Immediate treatment includes administering honey or corn syrup by rubbing on the gums of the cat (even if unconscious, but not if in seizures). Symptomatic hypoglycemia in cats is a medical emergency and the cat will require professional medical attention. The honey/corn syrup should continue to be administered on the way to the vet, as every minute without blood sugar causes brain damage.

A cat with hypoglycemia according to a blood glucose meter (<2.2 mmol/L or 40 mg/dL), but with no symptoms, should be fed as soon as possible. Hypoglycemic cats that refuse to eat can be force-fed honey or corn syrup until they stabilize.

Mild hypoglycemic episodes can go unnoticed, or leave evidence such as urine pools outside the litter box. In these cases the blood sugar will probably appear paradoxically high upon the next test hours later, since the cat's body will react to the low blood sugar by stimulating the liver to release stored glycogen.

Remission

Remission occurs when a cat no longer requires treatment for diabetes mellitus, and has normal blood glucose concentrations for at least a month.^[25]

Approximately one in four cats with type 2-like diabetes achieve remission. Some studies have reported a higher remission rate than this, which may in part be due to intensive monitoring that is impractical outside of a research environment. Research studies have implicated a variety of factors in successful remission; in general, the following factors increase the likelihood of remission:^[25]

• Diabetes was diagnosed a few months ago
• The cat has no other serious disease
• Treatment includes insulin glargine administered twice daily
• The cat is monitored frequently during the first few months of treatment
• The cat eats a diet low in carbohydrates and high in protein.

Cats may present with type-2 (insulin-resistant) diabetes, at least at first, but hyperglycemia and amyloidosis, left untreated, will damage the pancreas over time and progress to insulin-dependent diabetes.^[26]

Glipizide and similar oral diabetic medicines designed for type-2 diabetic humans have been shown to increase amyloid production and amyloidosis, and therefore may reduce likelihood of remission.^[12]

Approximately one third of cats which achieve remission will later relapse.^[25]

Epidemiology

Diabetes mellitus is rare in cats younger than five years old.^[27] Burmese cats in Europe and Australia have increased risk of developing diabetes mellitus; American Burmese cats do not have this increased risk due to genetic diffences between American Burmese and Burmese in other parts of the world.^[28]

References