Diabetes in cats and dogs

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Diabetes mellitus strikes 1 in 400 cats and a similar number of dogs, though recent veterinary studies[1][2][3] note that it is becoming more common lately in cats. Symptoms in dogs and cats are similar to those in humans. Generally, most dogs and about 5-20% of cats experience type-1 (insulin-dependent) diabetes, rather than the type-2 that's now becoming common in obese humans. The other 80-95% of cats experience type-2 diabetes.[4]. 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 blindness in dogs, increasingly weak legs in cats, and eventually malnutrition, ketoacidosis and/or dehydration, and death.

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[edit] Symptoms

Cats and dogs 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 less than seven years old, though younger dogs are more susceptible to Type-1 (juvenile) diabetes. The first obvious symptoms are a sudden weight loss or 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 dogs, the next symptom is vision problems and cataracts, while in cats the back legs may become weak and the gait may become stilted or wobbly. 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. A test can also be performed with a home glucose meter by obtaining a blood sample with a lancet via an ear prick, paw prick or, in dogs, a lip 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. Dehydration is also common by this point and death can follow quickly.

[edit] 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.[1][2] Cats usually seem to do best with long-lasting insulins and low carbohydrate diets[5], while dogs have varying "best" treatments depending on the individual case.[6]

[edit] Diet

Diet is a critical component of treatment, and is in many cases effective on its own. For example, a recent mini-study[3] 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, in dogs and perhaps cats, turned into blood glucose much more slowly and evenly than carbohydrates, reducing blood-sugar highs right after mealtimes.

Latest veterinary good practise is to recommend a low carbohydrate diet for cats[7][8], and a high-fiber, moderate-carb diet for dogs. In dogs another alternative is to feed a normal healthy diet but give mealtime insulin bolus supplements. Dogs with pancreatitis, a fairly common condition for diabetic dogs, often need a restricted-fat diet.[9]

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. These lists of common commercial cat foods and their carbohydrate energy content are kept up-to date. You can use the cat food calculator found at http://www.scheyderweb.com/cats/catfood.html to determine the carbohydrates and calories in any cat food, though numbers in American brands are given as minimums and maximums rather than actual estimates, and may be very inaccurate.

[edit] Pills

Oral medications like Glipizide that stimulate the pancreas promoting insulin release, (or in some cases, reduce glucose production) work in some small proportion of cats (Most dogs are Type I diabetics so oral hypoglycemic drugs are usually not prescribed for them), but these drugs may be completely ineffective if the pancreas is not working. Worse, these drugs have been shown in some studies[4] to damage the pancreas further, reducing the chances of remission for cats. They have also been shown to cause liver damage. Many are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor, (many cats are easier to inject than to pill) and injections are more effective in almost all cases.

[edit] 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's important for the pet to avoid large meals, 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 for most cats[10], since insulin usually metabolizes faster in cats than in dogs[11] or humans; an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat[12].

For dogs, either of the above two methods may be used. For example, a basal-only method combined with a high-fiber diet, or a basal-bolus method along with a normal canine diet, can be effective.

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[13], 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.

Caninsulin [5], known in the USA as Vetsulin [6], made by Intervet [7] (owned by Akzo Nobel), is a brand of pork-based insulin, which is designed for dogs, and is available both through veterinarians and pharmacies with a veterinarian's prescription, depending on the country [8]. Although not approved, and sometimes having less than optimal action[14], Caninsulin can also used for the ex-label treatment of diabetes mellitus in cats and pet rabbits [9] and guinea pigs.

Two new ultra-slow time-release synthetic human insulins are just becoming available in 2004 and 2005 for improving basal stability, generically known as Insulin Detemir ("Levemir")[10] and Insulin Glargine ("Lantus")[11]. A mini-study at the University of Brisbane, Australia[12] has had remarkable results with Insulin Glargine in cats. No studies have yet been performed on pets with detemir/Levemir, but early anecdotal evidence[13] shows that it is also very effective on cats.

[edit] Neuropathy in cats

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. (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 often heals on its own within 1 to 3 months once blood sugar is regulated, but anecdotal evidence[15][16][17] points to a faster recovery rate with methylcobalamin supplements.

[edit] Blindness in dogs

Dogs' eyes are highly sensitive to high blood sugar, and will have blurred vision, cataracts, or even total blindness after as little as a few days at blood glucose concentration above 14mmol/L (250 mg/mL). Cataracts may be treated later, but blindness is permanent in some cases. Fortunately, as dogs rely considerably on their senses of smell and hearing, blindness is less of a disability than might otherwise be expected.

[edit] Dosage and regulation

Cats and dogs 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 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)[18]. Cat metabolize insulin about twice as fast as humans[19], 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 or even many months. 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 recommended method is to Start Low - Go Slow:

  1. Have an initial blood curve taken over 24 hours at the vet and receive an initial dosage recommendation.
  2. The initial dosage will be very conservative (low) (usually between 0.5 and 2 units daily, split into 12-hour dosages) and may not affect the pet's symptoms noticeably at first. This is necessary because although high blood sugar can kill within weeks, low blood sugar can kill in minutes. Dosage must be increased gradually and carefully. The usual recommended method is to increase the dose by 1/2 to 1 unit every 7 to 14 days, followed by further glucose testing. An initial decrease may also be necessary -- it is fairly common for the initial recommendation to be a little bit too high, especially if it was estimated by weight. See Chronic Somogyi Rebound below. Buying an inexpensive blood glucose meter and testing for yourself just before each shot and at midpoint is essential -- it will save many expensive trips to the vet, avoid dangerous overdoses, and give you a better handle on the pet's ongoing condition. Urine strips are not accurate enough for this.
  3. Your pet is "regulated" when its blood glucose remains within an acceptable range all day, every day. Acceptable varies somewhat between cats, dogs, and vets, but is roughly from 5 to 16.7 mmol/L (90 to 300 mg/dL in the USA) for cats, and between 5 and 14 (90 to 250) for dogs. (The range is wider for diabetic animals than non-diabetic, since shots cannot replicate the accuracy of a working pancreas.) It's important, though, that the glucose level be in the lower half of that range for as much of the day as possible. If you are not doing home glucose testing, some vets recommend that you stop increasing the dosage when the dog or cat is drinking normally, urinating normally, and eating normally, although organ damage may continue in some cases until glucose is below the "Renal Threshold" -- testing urine with keto/glucostix will show when this has been achieved.
  4. Obstacles to regulation:
  • Sometimes your pet will suddenly appear to need less insulin than before. If this happens (their blood sugar will go lower than usual one day), drop the dose immediately and call your vet. If testing just before an injection, and the reading is much lower than expected, it may be wisest to skip that dose and continue retesting every 2-3 hours. If the drop is dramatic and leads to a hypoglycemic episode (see below), the cat's sensativit to insulin may increase dramatically. You should consider dropping their dose after consulting your veterinarian, and raise it only by half to one unit per 5-7 days, as before.
  • Sometimes your pet's blood sugar will suddenly seem much higher than usual. This is often not a good time to increase their insulin dosage -- quite the opposite. It often indicates that a low blood sugar condition (or rapid sugar drop) was experienced a few hours before, and a Somogyi rebound is in progress. To be sure, drop the next dose by 15%-50% and take glucose readings every 4 to 8 hours until the glucose levels out. Then wait a few more days for the Somogyi hormones to decrease in the body, and then you can increase again by 0.5-unit steps every 5-7 days. If you experienced this rebound, chances are that your original dose was too high, so you should try to find an ideal dose at a lower point.
  • Chronic overdose masked by Somogyi: A dose that is fractionally 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-carb cat/dog food: Many commercial foods (especially "Light" foods) are extremely high in cereals and therefore carbohydrates. The extra carbohydrates will keep the cat or dog's blood sugar high, and if you're free-feeding may also make the blood sugar curve over the course of the day unpredictable. In general, canned foods are lower in carbohydrates than dry ones, and canned "kitten" foods lower still. Recent studies[14] show that cats' diabetes can be better regulated and even sometimes cured with a low carbohydrate diet. This may not apply to dogs. If switching to a lower-carbohydrate food, do it gradually and lower the insulin dosage appropriately, with your vet's help. 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 and dogs. 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. 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.

[edit] Blood sugar guidelines

Absolute numbers vary between pets, and with meter calibrations. The numbers below are as shown on a typical home glucometer while hometesting blood glucose, not necessarily the more accurate numbers a vet would see (though many vets use meters similar to those used in hometesting). For general guidelines only, the levels to watch are approximately:

mmol/L mg/dL(US)
<2.2 <40 Readings below this level are usually considered hypoglycemic when giving insulin, even if you see no symptoms of it. Treat immediately[20]
2.2-7.5 40-130 Non-diabetic range[21] (usually unsafe to aim for when on insulin, unless your control is very good). These numbers, when not giving insulin, are very good news.
3.2-4.4 57-79 This is an average non-diabetic pet's level[22][23], but leaves little margin of safety for a diabetic on insulin. Don't aim for this range, but don't panic if you see it, either. If the number is not falling, it's healthy.
5 90 A commonly cited minimum safe value for the lowest blood sugar of the day
7.8 140 According to the American Association of Clinical Endocrinologists (AACE)[24], threshold above which organ and pancreatic damage may begin[25].
5.5-10
100-180
 Commonly used target range for diabetics, for as much of the time as possible.
<10-15 <180-270 "Renal threshold for glucose", when excess glucose from the kidneys spills into the urine and roughly when the pet begins to show diabetic symptoms. See Hyperglycemia in the Pet Diabetes Wiki for long-term effects of high blood glucose on cats and dogs.
14 250 Approximate maximum safe value for the highest blood sugar of the day, in dogs, who are more sensitive to high blood sugar. Dogs can go blind at this level. Cats should try to stay below this too. Check for ketones.
16.7 300 Approximate maximum safe value for the highest blood sugar of the day, in cats, to avoid neuropathy and complications. Some cats can go on long-term at this level or higher, but there will be side effects eventually[15]. Check for ketones.
>20 >360 Check for ketones frequently, be sure you are giving insulin. Cats are much more resilient than dogs or humans at these high levels; nevertheless, the blood sugar should be lowered. The cat or dog can feel any of numerous ill effects both short and long-term, see Hyperglycemia in the Pet Diabetes Wiki for details.

The regulation process is described in more detail here.

[edit] Detecting and avoiding chronic somogyi rebound

Oddly, too little insulin means pre-shots are too high and too much insulin often also means pre-shots are too high. This "Somogyi effect" is often noted by those who test their pets' blood glucose at home.

The reason: Anytime the glucose level drops too far or too fast, the cat or dog 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.[16] [17].

Even when raising the insulin dose slowly and carefully, it's 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. The pet may be a bit less responsive to the same dose the next shot, from those other hormones. Repeating the overdose on subsequent days, and checking only pre-shot readings or urine glucose, can give the dangerously wrong impression that more insulin is needed! Remember to check occasionally at the expected nadir (low point) as well.

It's unusual to be monitoring glucose right when this happens, and typical to just continue the overdose, leading to a repeated rebound situation. So it's good to learn to recognize the patterns of repeated rebound.

  • A typical rebound pattern, most often seen with long-acting insulins, is a high, flat, unresponsive blood sugar over a period of days. Sometimes, often when raising dosage, this high flat curve will be punctuated by sudden drops to very low values, (with possible hypoglycemic events) followed by a fast return to high unresponsive numbers. (It's the sudden dip that distinguishes this pattern from inadequate insulin!)
  • When using shorter-acting insulins, repeated Somogyi rebound may manifest instead as rapidly alternating high and low blood sugar numbers with no apparent logic. The highs and lows will both be exaggerated compared to what you'd see on a smaller dose.

It's not always easy to tell a rebound from a regular curve showing insulin action ending normally. One way to tell the difference is to take a "curve" (repeated tests every 2 hours starting with the insulin shot) on a weekend and look for the shape of the curve. If the curve is valley-shaped, and gradual, then you are not seeing Somogyi rebound. Other shapes should arouse suspicion. In particular, if the rise after peak action is faster and rises higher than the original pre-insulin level and the original fall in blood sugar, you have good cause to consider rebound. The only sure way to check is to reduce dosage and look for a better-shaped curve.

A fairly sure sign: Anytime blood glucose numbers seem higher after dosage is raised, consider the possibility of a somogyi rebound. But other things can cause unexpectedly high blood glucose too, so look for a clear correlation with dosage changes.

[edit] Hypoglycemic episode

An acute hypoglycemic episode (very low blood sugar) can happen even if you are 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 (<2.2mmol/L or 40mg/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 kitty 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), and requires a lowered insulin dosage for the next few days. The Somogyi rebound may also occur when the pet's blood glucose drops too rapidly, even if it never actually reaches a low reading.

[edit] Remission in cats

It is in many cases possible to induce remission (a temporary or permanent freedom from insulin-dependence) in type-2 diabetic cats. (This appears to be unique to cats, unfortunately for dogs and humans.) There is growing agreement among experts[18][19] that a combination of low carbohydrate healthy diet, well-chosen 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[26]. 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 [20] in which diabetes in cats is perpetuated, if not always caused, by a combination of glucose toxicity[27] 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[28].

Note that Glipizide and similar oral diabetic medicines designed for type-2 diabetic humans have been shown to increase amyloid production and amyloidosis.[21]

[edit] References

  1. ^ Fat Cats Facing Diabetes Epidemic, The Guardian, August 7 2007
  2. ^ Journal of Feline Medicine and Surgery (2007) 9, 289e299 doi:10.1016/j.jfms.2007.02.001
  3. ^ Feline Diabetes is Nutrition Key, Vet Tech Blog, Feb 2006
  4. ^ Canine and Feline Diabetes Mellitus: Nature or Nurture?, J. Rand et al.
  5. ^ Feline Diabetes: Pathogenesis and Treatment. Rand, Marshall 2006
  6. ^ Achieving Optimal control in diabetic dogs. Fleeman, Rand 2005
  7. ^ Frank GR, Anderson W, Pazak H, Hodgkins E, Ballam J and D Laflamme. 2001. Use of a High Protein Diet in the Management of Feline Diabetes Mellitus. Veterinary Therapeutics. 2:238-246.
  8. ^ Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus. Bennett & Greco et al. 2005
  9. ^ Achieving optimal control in Diabetic dogs. Fleeman, Rand. 2005
  10. ^ Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats. Wallace et al.
  11. ^ Absorption kinetics of regular and isophane (NPH) insulin in the normal dog. Goeders et al
  12. ^ Insulin Therapy in cats with Diabetes Mellitus, Moise & Reimers, 1983
  13. ^ Insulin therapy in cats with diabetes mellitus, Moise & Reimers, 1983
  14. ^ Intervet's Caninsulin website shows idealized feline glucose curve, with dramatic action directly contradicting the ideal stable glucose targets stated on the same page.
  15. ^ Delano Report on Methyl-B12 and Neuropathy
  16. ^ Laurie Ulrich's story on Methylcobalamin and Neuropathy
  17. ^ Testimonials on Feline Diabetes message board re: Methylcobalamin and Neuropathy
  18. ^ NPH insulin lasts only 7.7 hours in cats
  19. ^ Intervet Caninsulin overview, mentions cats faster metabolism of insulin, see page 4
  20. ^ Treating Hypoglycemia-Gorbzilla.com
  21. ^ VIN: Determination of Rate Natural Blood Glucose in Persian Cats, say "50-160mg/dl"
  22. ^ Feline Diabetes message board survey on non-diabetic cats' bg levels
  23. ^ Dr. E. Hodgkins, 2004, says "around 60mg/dl (3.4 mmol/L)"
  24. ^ AACE-Call For Better Glucose Management-Hospitalized Patients
  25. ^ organ damage threshold studies
  26. ^ Understanding Feline Diabetes Mellitus, Dr. J. Rand, University of Queensland
  27. ^ Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in pancreatic beta cells in diabetes, RP Robertson, JBC
  28. ^ Islet Amyloid and Progression of Type-II Diabetes, Hayden, JOP

[edit] Further reading

[edit] General information

[edit] Specific topics

[edit] Inducing remission in cats

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