Diabetes in cats

Diabetes mellitus in cats is a chronic disease that affects carbohydrate metabolism due to either an insufficient insulin response or insulin resistance. Like diabetes in humans, it is characterized by chronically high blood glucose. Diabetes strikes 1 in 400 cats, though recent veterinary studies[1][2][3] note that it has become increasingly common. Symptoms in cats are similar to those in humans. Diabetes in cats occurs less frequently than in dogs.[4] 80-95% of diabetic cats experience something similar to type-2 diabetes,[5] 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,[6] 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

Progression of untreated diabetes in cats is very similar to that in humans. 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 condition is rare in cats younger than seven years old.

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.

In cats the back legs may become weak and the gait may become stilted or wobbly (peripheral neuropathy). A fasting glucose blood test (the same as used on the Atkins diet) 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.

Treatment

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.[7][8] Cats do best with long-lasting insulin and low carbohydrate diets.[9] 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[10] 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[11][12] 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.[13] 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.

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,[14] and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies[15] 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 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, attempts 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, 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,[16] since insulin usually metabolizes faster in cats than in humans or dogs.[17] For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat.[18]

Cats (and dogs) may be treated with animal insulin (porcine-based is most similar to a dog's natural insulin, bovine-based for a cat), 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. One of the popular human synthetic insulins, Humulin N /Novolin N/ NPH, is reasonable for dogs, but is usually a poor choice for cats,[18] since cats metabolize 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 bovine/porcine-derived PZI,[19] 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 porcine-based insulin, which is approved for dogs and cats,[20] and is available both through veterinarians and pharmacies with a veterinarian's prescription, depending on the country. Vetsulin was recalled in the USA in November 2009 due to inconsistent strength. According to the manufacturer's website, the insulin's action profile was long and flat in dogs, but in cats was similar to that of NPH insulin, and lowered blood sugar quickly, but for only about 6–8 hours. Vetsulin is available again in the USA as of April 2013.[21]

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 positive results with insulin glargine in cats.[22] 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, 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

Timing

Cats may in some cases 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. In other cases where the pet 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.[16] The 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).

Regulation

The goal at first is to regulate the cat'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 cat during the whole day, or most of it.

The most successful documented method is Tight Regulation with Lantus or Levemir.[23][24]

Typical obstacles to regulation include:

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). At this point the size difference in human and animal red blood cells can create inaccurate readings.[25] The numbers below are as shown on a typical home glucometer. 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 no symptoms of it are seen. Treat immediately[26]
2.2-7.5 40-130 Non-diabetic range[27] (usually unsafe to aim for when on insulin, unless your control is very good). These numbers, when not giving insulin, are very good news.
3.38-6.88 61-124[28] This is an average non-diabetic cat's level,[29] 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
5.5-10
100-180
 Commonly used target range for diabetics, for as much of the time as possible.
7.8 140 According to the American Association of Clinical Endocrinologists (AACE), threshold above which organ and pancreatic damage may begin in humans.[30]
<13.33-15 240[31]-270 Feline Renal threshold for glucose, when excess glucose from the kidneys spills into the urine and roughly when the cat begins to show diabetic symptoms. See Hyperglycemia for long-term effects of high blood glucose on cats.
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. 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 can feel any of numerous ill effects both short and long-term, see hyperglycemia for details.

A Glucometer for Veterinary use is available from i-SENS, Inc. South Korea with the brand name VETMATE. VETMATE is a portable POCT device, needs just 0.4㎕ of blood sample and gives results in just 5 seconds. The measuring range is 10–600 mg/dL [0.6-33.3 mmol/L] and is based on Enzyme: GDH-FAD. Added to that VETMATE, No coding is required, has a Hypoglycemia indicator, comes with a Strip ejection button and Auto back-lighted LCD. VETMATE has a feature of 7, 14, 30-day test averages [total], 5-time set alarms. Based on BIOSENSOR Technology, VETMATE is especially calibrated for dogs & cats. VETMATE also offers a data port for PC Connectivity.

Complications

Neuropathy

The weak legs syndrome found in many diabetic cats is a form of 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.[32] 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[33][34] points to a faster and more complete recovery with methylcobalamin supplements.

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. This phenomenon was first documented by a Dr. Michael Somogyi. If the body has no glycogen reserves, there will be no rebound effect and the cat will just be hypoglycemic. [35]

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.)

There is no research data that supports the theory that the Somogyi effect ever actually occurs in cats.[36]

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.

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[10][29] 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.[37] 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[38] in which diabetes in cats is perpetuated, if not always caused, by a combination of glucose toxicity[38] 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.[39]

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.[15]

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. Testing the level of insulin-like growth factor-1 (IGF-1) in the blood is the primary test for feline acromegaly.[40]

References

  1. ↑ Fat Cats Facing Diabetes Epidemic, The Guardian, August 7, 2007
  2. ↑ McCann TM, Simpson KE, Shaw DJ, Butt JA, Gunn-Moore DA (August 2007). "Feline diabetes mellitus in the UK: the prevalence within an insured cat population and a questionnaire-based putative risk factor analysis". J. Feline Med. Surg. 9 (4): 289–99. doi:10.1016/j.jfms.2007.02.001. PMID 17392005.
  3. ↑ Feline Diabetes is Nutrition Key, Vet Tech Blog, Feb 2006
  4. ↑ Diabetes in cats
  5. ↑ Canine and Feline Diabetes Mellitus: Nature or Nurture?, J. Rand et al.
  6. ↑ Understanding Feline Diabetes Mellitus, Rand, J.S. and Marshall, R, Waltham Focus Journal 2005, 15:3
  7. ↑ Insulin Glargine and a high protein-low carbohydrate diet are associated with high remission rates in newly diagnosed diabetic cats.
  8. ↑ Feline Diabetes, Remission, and protocols with various Insulins
  9. ↑ Feline Diabetes: Pathogenesis and Treatment. Rand, Marshall 2006
  10. 1 2 Study Shows 'Catkins' Diet Helps Cats Beat Diabetes
  11. ↑ Frank GR, Anderson W, Pazak H, Hodgkins E, Ballam J, Laflamme D (2001). "Use of a High Protein Diet in the Management of Feline Diabetes Mellitus". Veterinary Therapeutics. 2 (3): 238–46. PMID 19746667.
  12. ↑ Bennett N, Greco DS, Peterson ME, Kirk C, Mathes M, Fettman MJ (April 2006). "Comparison of a low carbohydrate-low fiber diet and a moderate carbohydrate-high fiber diet in the management of feline diabetes mellitus.". J. Feline Med. Surg. 8 (2): 73–84. doi:10.1016/j.jfms.2005.08.004. PMID 16275041.
  13. ↑ Dr. Lisa Pierson, Know the Basics of Feline Nutrition
  14. ↑ Veterinary Partner-Insulin Alternatives
  15. 1 2 Hoenig M, Hall G, Ferguson D, et al. (1 December 2000). "A feline model of experimentally induced islet amyloidosis". Am. J. Pathol. 157 (6): 2143–50. doi:10.1016/S0002-9440(10)64852-3. PMC 1885761Freely accessible. PMID 11106586.
  16. 1 2 Wallace MS, Peterson ME, Nichols CE (October 1990). "Absorption kinetics of regular, isophane, and protamine zinc insulin in normal cats". Domest. Anim. Endocrinol. 7 (4): 509–15. doi:10.1016/0739-7240(90)90008-N. PMID 2261761.
  17. ↑ Goeders LA, Esposito LA, Peterson ME (January 1987). "Absorption kinetics of regular and isophane (NPH) insulin in the normal dog". Domest. Anim. Endocrinol. 4 (1): 43–50. doi:10.1016/0739-7240(87)90037-3. PMID 3333933.
  18. 1 2 Moise NS, Reimers TJ (January 1983). "Insulin therapy in cats with diabetes mellitus". J. Am. Vet. Med. Assoc. 182 (2): 158–64. PMID 6298164.
  19. ↑ http://www.felinediabetes.com/pzi.htm
  20. ↑ http://www.vetsulin.com/PDF/Vetsulin_Dear_Doctor_Letter.pdf
  21. ↑ http://www.vetsulin.com/vet/Product_Update.aspx
  22. ↑ http://www.felinediabetes.com/glargine.htm
  23. ↑ J Feline Med Surg. 2009 Aug;11(8):668-82. Epub 2009 Jul 9. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. Roomp K, Rand J. Department of Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Saarbrücken, Germany.
  24. ↑ Tilly's Diabetes Homepage, K Roomp, Accessed 13 Jun 2010
  25. ↑ Diabetes Mellitus-Glucometers-Dr. William A. Schall-ACVIM-DVM 360 2009
  26. ↑ Treating Hypoglycemia-Gorbzilla.com
  27. ↑ VIN: Determination of Rate Natural Blood Glucose in Persian Cats, say "50-160mg/dl"
  28. ↑ Merck Veterinary Manual
  29. 1 2 Dr. E. Hodgkins, 2004, says "around 60mg/dl (3.4 mmol/L)"
  30. ↑ organ damage threshold studies
  31. ↑ Merck Veterinary Manual
  32. ↑ Logical Approach to Weakness and Seizures-David B. Church-WSAVA 2009
  33. ↑ Delano Report on Methyl-B12 and Neuropathy
  34. ↑ Laurie Ulrich's story on Methylcobalamin and Neuropathy
  35. ↑ Somogyi Phenomenon at eMedicine
  36. ↑ http://jfm.sagepub.com/content/18/8/587.full
  37. ↑ Understanding Feline Diabetes Mellitus, Dr. J. Rand, University of Queensland
  38. 1 2 Robertson RP (October 2004). "Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes". J. Biol. Chem. 279 (41): 42351–4. doi:10.1074/jbc.R400019200. PMID 15258147.
  39. ↑ Islet Amyloid and Progression of Type-II Diabetes, Hayden, JOP
  40. ↑ Niessen, Stijn J. M.; Forcada, Yaiza; Mantis, Panagiotis; Lamb, Christopher R.; Harrington, Norelene; Fowkes, Rob; Korbonits, Márta; Smith, Ken; Church, David B. (29 May 2015). "Studying Cat ( Felis catus ) Diabetes: Beware of the Acromegalic Imposter". PLOS ONE. 10 (5): e0127794. doi:10.1371/journal.pone.0127794. ISSN 1932-6203.

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