Diabetes in cats

Diabetes mellitus strikes 1 in 400 cats, though recent veterinary studies  note that it has become increasingly common. Symptoms in cats are similar to those in humans. Diabetes in cats occurs more frequently 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 definitely treatable, and need not shorten the animal's life span or life quality. In type-2 cats, prompt effective treatment can even 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, and it may escape notice for a while. The condition is unusual in cats younger than seven years old. The first obvious symptoms are a sudden weight loss (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. In cats the back legs may become weak and the gait may become stilted or wobbly (peripheral neuropathy). A quick test at this point can be done using urine keto/glucose strips (the same as used on the Atkins diet) with the animal. If the keto/glucose strips show glucose in the urine, diabetes is indicated. If a strip shows ketones in the urine, the animal should be brought to an emergency clinic right away. Testing can also be performed with a home glucose meter by obtaining a blood sample with a lancet via an ear prick or paw prick.

Owners should watch for noticeable thinning of the skin and apparent fragility: these are also serious and indicate that the animal is metabolizing (breaking down) its own body fat and muscle to survive. Lethargy or limpness, and acetone-smelling breath are acute symptoms indicating likely ketoacidosis and/or dehydration and demand emergency care within hours.

Treatment
Diabetes can be treated but is life-threatening if left alone. Early diagnosis and treatment by a qualified veterinarian can help, not only in preventing nerve damage, but in some cases, in cats, can even lead to remission. Cats usually seem to do best with long-lasting insulins and low carbohydrate diets.

Diet
Diet is a critical component of treatment, and is in many cases effective on its own. For example, a recent mini-study 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 turned into blood glucose much more slowly and evenly than carbohydrates, reducing blood-sugar highs right after mealtimes.

Latest veterinary good practice is to recommend a low carbohydrate diet for cats rather than the formerly-recommended high-fiber diet.

It's now becoming clear that lower carbohydrate diets will significantly lower insulin requirements for diabetic cats. Carbohydrate levels are highest in dry cat foods (even the expensive "prescription" types) so cats are best off usually with a low carbohydrate healthy canned diet. Some prescription canned foods made for diabetic cats are effective, but some ordinary ones work just as well. Between 3 and 9% calories from carbohydrates seems to be optimal.

Pills
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, and these drugs may be completely ineffective if the pancreas is not working. Worse, these drugs have been shown in some studies to damage the pancreas further, reducing the chances of remission for cats. They have also been shown to cause liver damage. Many 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 in almost all cases.

Insulin injections
Humans with Type-1 diabetes are often treated with a "basal plus bolus" method, where a long-acting insulin is injected once or twice daily to provide a "basal" insulin level, then shorter-acting insulin is used just before mealtimes.

For cats, a "basal" method is usually employed instead—a single slow-acting dose, twice daily, along with a very low carbohydrate diet, attempts to keep the blood sugar within a recommended range for the entire day. In this case, it is important for the pet to avoid large meals or high-carbohydrate food, since they can seriously affect the blood sugar (meals may also be timed to coincide with peak insulin activity). Once-daily doses are not recommended, since insulin usually metabolizes faster in cats than in humans or dogs. For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat.

Cats and dogs may be treated with animal insulins (pork-based is most similar to a dog's natural insulin, beef-based for a cat), or with human synthetic insulins. The best choice of insulin brand and type varies between pets and may require some experimentation. One of the popular human synthetic insulins, Humulin N /Novolin N/ NPH, is reasonable for dogs, but is usually a poor choice for cats, since cats' metabolize (most) insulin about twice as fast. The Lente and Ultralente versions were therefore very popular for feline use until summer 2005, when Eli Lilly and Novo Nordisk both discontinued them.

Until the early 1990s, the most recommended type for pets was beef/pork-derived PZI, 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), made by Intervet, is a brand of pork-based insulin, which is approved for dogs and cats, and is available both through veterinarians and pharmacies with a veterinarian's prescription, depending on the country. Note, though, that Vetsulin was recently recalled due to inconsistent strength and is no longer used in the USA. According to the manufacturer's website, this insulin's action profile is long and flat in dogs, but in cats very similar to that of NPH insulins, and lowers blood sugar quickly, but for only about 6–8 hours.

Two new ultra-slow time-release synthetic human insulins became available in 2004 and 2005 for improving basal stability, generically known as insulin detemir (Levemir) and insulin glargine (Lantus). Studies at the University of Queensland, Brisbane, Australia have had remarkable results with insulin glargine in cats. Follow-up research Roomp and Rand, Vet Intern Med 2008, 22 (3):791 shows that Levemir can be used with a similar protocol and that either insulin, on this protocol, leads in most uncomplicated feline cases to remission, with the most success being in cats who start on these protocols as soon as possible after diagnosis.

Neuropathy
The weak legs syndrome found in many diabetic cats is a form of neuropathy, in particular caused by damage to the myelin sheath of the peripheral nerves caused by glucose toxicity and cell starvation, which are caused by chronic hyperglycemia. (There are other conditions that can cause weak legs too, consult your vet before assuming neuropathy.) Most common in cats, the back legs become weaker until the cat displays "Plantigrade stance", standing on its hocks instead of on its toes as usual. 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.

Dosage and regulation
Cats may in some cases have their mealtimes strictly scheduled and planned to match with injection times, especially when on insulins with a pronounced peak action like Caninsulin/Vetsulin or Humulin N. In other cases where the pet free-feeds and normally eats little bits all day or night, it may be best to remain on this schedule and try to use a very slow-acting insulin to keep a constant level of blood glucose. Consult your veterinarian. Note that some veterinarians still use the outdated recommendation of using Humulin "N" or NPH insulin for cats. This insulin is too fast-acting for most cats (though fine for dogs and humans). Cats metabolize insulin about twice as fast as humans, and the often-effective slower-acting Lente and Ultralente (Humulin L and Humulin U) insulins are being discontinued (as of 2005), so most cats are now using either the veterinary PZI insulins, or the new full-day analogs glargine (Lantus) and detemir (Levemir).

The goal at first is to "regulate" the pet's blood glucose, which may take a few weeks. This process is basically the same as in type-1 diabetic humans. The goal is to keep the blood glucose values in a comfortable range for the pet during the whole day, or most of it.

The most successful documented method is Tight Regulation with Lantus or Levemir.


 * Typical obstacles to regulation:


 * Chronic overdose masked by Somogyi: A dose that is too high can easily cause a Somogyi rebound, which can look like a need for more insulin.   This condition can continue for days or weeks, and it's very hard on the cat's metabolism.  See more on this topic in the Somogyi section below.


 * High-carbohydrate cat food: Many commercial foods (especially "light" foods) are extremely high in cereals and therefore carbohydrates. The extra carbohydrates will keep the cat's blood sugar high, and if you're free-feeding may also make the blood sugar curve over the course of the day volatile and unpredictable. In general, canned foods are lower in carbohydrates than dry ones, and canned "kitten" foods lower still.  Recent studies show that cats' diabetes can be better regulated and even sometimes cured with a low carbohydrate diet. If switching to a lower-carbohydrate food, do it gradually and lower the insulin dosage appropriately, using home blood-glucose testing several times daily to be sure your insulin dose is being adjusted properly.  If your cat is on a special diet for pancreatitis, chronic renal failure, or any other condition, consult your vet for the appropriate diet for that condition plus diabetes.


 * Wrong insulin: Different brands and types of insulin have idiosyncratic effects on different cats.  If you've settled on a dose that seems to keep the pet's blood sugar within range at peak effectiveness, but the sugar readings remain dangerously high at shot times, the insulin may not be lasting long enough for your pet, or may not be the best choice. Testing blood sugar more frequently (for example, at 6, 8, 10 and 12 hours after shot) will determine if the insulin is lasting long enough. Switching to a slower-acting or a better-tolerated insulin for that pet, and lowering the dose initially to be safe, may be the next step.

Blood sugar guidelines
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). It is at this point where the size difference in human vs animal red blood cells can create inaccurate readings. The numbers below are as shown on a typical home glucometer while home-testing blood glucose, not necessarily the more accurate numbers a vet would see (though many vets use meters similar to those used in home testing). For general guidelines only, the levels to watch are approximately:

Detecting and avoiding chronic Somogyi rebound
Too much insulin may result in increase of blood glucose (BG). This "Somogyi effect" is often noted by pet owners who monitor their pets' blood glucose at home.

The reason: anytime the glucose level drops too far or too fast, the animal's organism may defensively dump glucose (converted from glycogen in the liver), as well as hormones epinephrine and cortisol, into the bloodstream. (If these are insufficient, hypoglycemia ensues!) The glycogen raises the blood glucose, the other two may make the pet insulin-resistant for a time. This phenomenon was first documented by a Dr. Michael Somogyi.

Even when raising the insulin dose slowly and carefully, it is possible to pass the correct dose and go on to an overdose. (A typical case is increasing bidaily dosage from 1 unit to 2, passing a correct dose of 1.5 units.) This may produce a rebound—a swift jump in blood glucose up from a dangerously low reading, to beyond the previous pre-shot level. Always consult your veterinarian when changing your pet's insulin, and consider smaller dose changes.

Hypoglycemic episode
An acute hypoglycemic episode (very low blood sugar) can happen even if one is careful, since pets' insulin requirements sometimes change without warning. The symptoms are depression/lethargy, confusion/dizziness, loss of excretory/bladder control, vomiting, and then loss of consciousness and/or seizures. As soon as possible, administer honey or corn syrup by rubbing it on the gums (even if unconscious, but not if in seizures), and rush it to the vet. Carry more honey or corn syrup with you on the way and keep rubbing it on the gums, where it can be absorbed—it could save the pet's life. Every minute without blood sugar causes brain damage. (Some recommend administering syrup anally if the animal is in seizures.)

If the pet has hypoglycemia according to the blood glucose meter (<2.2 mmol/L or 40 mg/dL), but no symptoms, give treats or food if possible. If they won't eat, try putting food in their mouth. If that doesn't work, administer some honey followed by food or cat treats, and continue to do so until the blood glucose is rising, and the latest insulin shot's peak action is past.

Sometimes a mild hypoglycemic episode will go unnoticed, or leave evidence such as an "accident" where a cat fails to make it to the litterbox. In these cases the blood sugar will probably appear paradoxically high upon the next test hours later, since the pet's body will react to the low blood sugar by stimulating the liver to release stored glycogen. This condition is known as Somogyi rebound (see link above). Consult your vet.

Diabetic ketoacidosis
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.

Remission
In most cases, it is possible to induce remission (a temporary or permanent freedom from insulin-dependence) in type-2 diabetic cats. This appears to be unique to cats. There is growing agreement among experts that a combination of a low-carbohydrate healthy diet, long-lasting insulin, and well-chosen dosage plans can in many cases partially heal a damaged pancreas and allow the cat's blood sugar to be controlled entirely by diet thereafter. (A low carbohydrate diet is usually required for the remainder of the cat's life.)

Remission is a realistic goal for treatment of type-2 diabetic cats (that is, 80–95% of all diabetic cats) who are properly regulated quickly. Chances of success are highest in the first few months after initial diagnosis, due to ongoing damage from glucose toxicity caused by hyperglycemia. This limited time window is a good reason to start with low carbohydrate diet and very slow-acting insulins, the most successful known combination, right away.

An explanation can be pieced together from recent studies in which diabetes in cats is perpetuated, if not always caused, by a combination of glucose toxicity and amyloidosis, such that the insulin-producing islets of the pancreas become clogged with amyloid deposits. 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.

If blood sugar is well controlled over a period of 2–3 months, glucose toxicity and amyloidosis cease to attack newly generated tissue, and many cats are able to regenerate some of the damaged pancreatic beta cells and slowly resume insulin production.

Note that Glipizide and similar oral diabetic medicines designed for type-2 diabetic humans have been shown to increase amyloid production and amyloidosis, and therefore likely reduce likelihood of remission.

Acromegaly
New research has shown that acromegaly might be a new leading cause for diabetes in cats, with prevalence ranging from 20-30% among diabetic cats