Genetic welfare problems of companion animals

 

Diabetes Mellitus

 

Breed: Burmese

 

Condition:  Diabetes Mellitus

Related terms:

Outline: Some families and populations of Burmese cats in some parts of the world appear to be predisposed to developing diabetes mellitus. It is thought that this is due to decreased sensitivity to the effects of the hormone insulin, with the result that the uptake of glucose by cells is reduced. This leads to elevated glucose concentrations in blood and urine. The disease effects of diabetes mellitus may cause feelings of malaise. The genes involved are not known.



 

Summary of Information

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1.           Brief description

In diabetes mellitus, there is a problem with the uptake of glucose from the blood into cells. Inadequate amounts of glucose enter the cells, denying the body’s tissues their main source of energy. As a consequence, and particularly after meals, blood glucose can reach abnormally high levels and this excess is excreted in the urine.

Normally, glucose uptake by cells is regulated by the hormone insulin. Subnormal levels of insulin can cause some forms of diabetes mellitus. However, the commonest cause of diabetes mellitus in cats is similar to what is called type II diabetes in humans. This is insulin resistant diabetes. In this form, the disease is caused by the tissues developing resistance to the effects of insulin, rather than by a lack of the hormone. It is a progressive disease, more commonly seen in older animals. Most affected cats are over eight years old and the average age is around 12 (Panciera et al 1990, Baral et al 2003).

In the early stages of type II diabetes, the pancreas responds to the high blood glucose levels that occur due to the insulin resistance of the body tissues, by producing more insulin. However, often by the stage in which the disease is diagnosed in cats, the pancreas has become exhausted and is unable to produce normal amounts of insulin so blood insulin levels may be low.

Commonly, the disease shows in one of two ways (Peterson et al 1994).

1. Uncomplicated diabetes. In this form, the high concentration of blood glucose causes excessive water loss as it is excreted in the urine, due to the osmotic effect of the glucose. Large volumes of dilute urine are produced and the cat drinks excessively to compensate for this fluid loss. There may also be some weight loss, despite the cat eating more than normal, as the cells of the body have to use other sources of energy to compensate for their inability to take in the glucose they need to function from the blood. In some cases, there may be damage to the nervous system that affects locomotion - resulting in affected animals showing a sinking down at the hocks (plantigrade posture) and walking with their hocks on the ground.

2. Ketoacidosis. Cats with diabetes are unable to use glucose as an energy source and use fats as an energy source instead. The metabolism of fatty acids in the liver results in the production of toxic substances called ketones. This affects blood electrolyte (salt) and acidity levels and leads to dehydration, weakness and loss of appetite (Peterson et al 1994). Affected cats may also show breathing problems and vomiting and diarrhoea (Peterson et al 1994). Cats with ketoacidosis are in a critical situation and without treatment they will die and even with treatment, may not survive. Treatment involves hospitalisation, fluid therapy and insulin treatment.

Treatment of uncomplicated diabetes in cats usually involves injections of insulin every 12 to 24 hours. A major concern in using insulin treatment is the danger of overdosing. The dose of insulin for effective control of blood glucose level is only a little lower than the dose that will cause a dangerous hypoglycaemia (low blood glucose level). Hypoglycaemia initially shows as weakness and can rapidly progress to signs of brain dysfunction including convulsions, coma and death (Peterson et al 1994).

 

 

2.           Intensity of welfare impact             

The severity of the welfare impact varies according to whether the diabetes is uncomplicated or complicated (eg ketoacidotic). Cats with the more severe forms, even if successfully treated for these, will usually continue to have welfare problems from the uncomplicated form of diabetes.

Affected cats are likely to feel malaise and discomfort associated with reduced appetite, increased thirst, vomiting, diarrhoea and weakness (Peterson et al 1994).

Cats with diabetes require multiple and repeated veterinary procedures. The condition requires interventions for diagnosis and to check for complications such as urinary tract infections. Treatment of the complicated forms of diabetes requires intensive care. This usually lasts only for a few days before the cat either dies or the condition improves to be classed as uncomplicated diabetes.

Long-term care of most diabetic cats requires insulin injections. The welfare implication of this varies: some cats tolerate injections easily but many come to resent the procedure and for some the injections become intolerable. Frequent monitoring with blood and urine tests are also required to ensure that appropriate treatment is being used and, again, the welfare impact of these interventions will vary according to their frequency and the character of the cat (Casella et al 2005). Over-dosing with insulin may cause episodes of hypoglycaemia which will cause malaise and may require intensive care.

Many cats with diabetes are euthanased because their owners cannot cope either with the necessary time commitment or the costs (Norsworthy 2003).

 

 

3.           Duration of welfare impact

 

Cats with the complicated forms of diabetes mellitus either recover (to live on with uncomplicated diabetes) or die within a few days. In uncomplicated diabetes mellitus, injections of insulin and blood and urine tests used to monitor the condition are required for the remainder of the cat’s life. Many cats will be treated for months or years.

 

4.           Number of animals affected

 

Diabetes mellitus is a common condition in cats. There is evidence that Burmese cats in the UK, Australia and New Zealand are particularly predisposed to the disease (Rand et al 1997, Wade et al 1999, Baral et al 2003, Rand et al 2004). Burmese cats in Australia are considered to be at about a 1 in 50 risk of developing diabetes at any age but around 10% of Burmese cats over the age of eight have diabetes (Baral et al 2003). They are affected about four times more than other cats (Rand et al 2004). There are certain families of Burmese cats in Australia in which around 10% have diabetes (Wade et al 1999).

 

5.           Diagnosis

Some other diseases have similar signs (eg hyperthyroidism and chronic renal disease) and the diagnosis of diabetes mellitus rests on detection of high levels of glucose in blood and urine. Measurement of fructosamine level also be useful for diagnosis and monitoring response to treatment (Link & Rand 2008). Diagnosis of the ketoacidotic form depends on detecting ketones in the blood or urine (Zeugswetter et al 2010).

 

6.           Genetics

 

The predisposition to diabetes in Burmese cats in some parts of the World and the observation that certain families have particularly high prevalence is evidence of a genetic influence (Wade et al 1999). The gene or genes involved have not been determined. It appears that the gene is not sex linked and may be recessive. The gene probably affects the sensitivity of peripheral cells to insulin (Rand et al 2004).

 

7.           How do you know if an animal is a carrier or likely to become affected?

There is no genetic test and there is no way to predict which animals are likely to develop diabetes mellitus in later life (except that this appears to be more likely if close relatives are affected). It is not known if the mutant gene or genes can be carried and passed on to offspring by animals that never develop the disease themselves, although this seems quite likely since it thought to be a recessive condition (Wade et al 1999).

 

8.          Methods and prospects for elimination of the problem

 

As far as we are aware there are no official schemes aimed at reducing the prevalence of diabetes mellitus in Burmese cats. As with other diseases with a suspected genetic influence, recommendations can only be made based on general principles. The disease typically has a late onset, after the age when cats are first bred. Breeding selectively from Burmese cats whose relatives have been free of the disease (and which have good breeding values) is likely to be effective in reducing the number of affected animals (Bell 2010). Breeding values take account of any available genetic information and the presence or absence of diseases both in the individual and its relatives. Progress in reducing the prevalence of diabetes mellitus in Burmese is likely to be facilitated by greater knowledge of the genetics that underlie the disease.

 

 


 

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1.           Clinical and pathological effects

 

Diabetes mellitus is the more common of the two types of diabetes. In diabetes mellitus, there is a problem with the uptake of glucose from the blood into cells. Inadequate amounts of glucose enter the cells, denying the body’s tissues their main source of energy. As a consequence, and particularly after meals, blood glucose can reach abnormally high levels and this excess is excreted in the urine (NB: the other type, diabetes insipidus, has a completely different cause and has a similar name only for historical reasons here we use the term 'diabetes' to refer only to diabetes mellitus).

Blood glucose levels and the uptake of glucose by cells is partly regulated by the hormone insulin. Insulin is produced in the pancreas and released into the blood in response to dropping glucose concentration. Diabetes mellitus can be caused either by insulin deficiency (as can occur as a consequence of pancreatic or pituitary disease) or as a result of tissues becoming insensitive to insulin (Feldhahn et al 1999, Rand 1999). This insulin resistant diabetes (known as type ll diabetes in humans) is the commonest form in cats and the usual form to affect Burmese.

It is a progressive disease, more commonly seen in older animals. Most affected cats are over eight years old and the average age is around 12 (Panciera et al 1990, Baral et al 2003). It is more common in neutered animals and in males (Rand et al 2004). Various factors may play a role in its development. Obesity is an important factor in the development of diabetes, as is inactivity (probably because the latter is also linked to obesity (Lederer et al 2003, Rand et al 2004). It is associated with some infections and inflammations, such as occur in dental disease (Rand et al 2004). A high carbohydrate diet may be important also (Rand et al 2004) perhaps because high blood glucose concentration can lead to reduced sensitivity to insulin.

On average, cats with diabetes are six times more resistant to the actions of insulin than normal cats (Rand 2009). In the early stages of type II diabetes the pancreas responds to the high blood glucose levels, that occur as a result of the insulin insensitivity of the tissues, by producing more insulin. However, often by the time the disease is diagnosed the pancreas is exhausted and blood insulin levels may be low.

Diabetes can also occur because of the primary loss of insulin producing cells in the pancreas. This is known as type I diabetes in humans. A similar condition can occur in cats with chronic pancreatitis (Forcada 2008).

Burmese cats are known to be predisposed to diabetes and it is suspected that this is due to a genetic predisposition to one of the forms outlined above. It is thought that it is not likely to be due to chronic pancreatitis as this is not a consistent finding in Burmese cats with diabetes (Lederer et al 2004).

Whatever the cause of elevated blood glucose concentration, permanently high levels cause problems (glucotoxicity - Rand 1999) that make the diabetes escalate. Persistently high blood glucose levels damage insulin producing cells, reducing insulin production and also reducing cell sensitivity to insulin.

Commonly, the disease shows in one of two ways (Peterson et al 1994).

 

1. Uncomplicated diabetes. In this form, the high concentration of blood glucose causes excessive water loss as it is excreted in the urine, due to the osmotic effect of the glucose. Large volumes of dilute urine are produced and the cat drinks excessively to compensate for this fluid loss. There may also be some weight loss, despite the cat eating more than normal, as the cells of the body have to use other sources of energy to compensate for their inability to take in the glucose they need to function from the blood. In some cases, there may be damage to the nervous system that affects locomotion - resulting in affected animals showing a sinking down at the hocks (plantigrade posture) and walking with their hocks on the ground.

2. Ketoacidosis. Cats with diabetes are unable to use glucose as an energy source and use fats as an energy source instead. The metabolism of fatty acids in the liver results in the production of toxic substances called ketones. This affects blood electrolyte (salt) and acidity levels and leads to dehydration, weakness and loss of appetite (Peterson et al 1994). Affected cats may also show breathing problems and vomiting and diarrhoea (Peterson et al 1994). Cats with ketoacidosis are in a critical situation and without treatment they will die and even with treatment, may not survive. Treatment involves hospitalisation, fluid therapy and insulin treatment.

(A third form, hyperosmotic non-ketotic diabetes mellitus occurs less commonly. This is also very serious. It is characterised by extreme dehydration with very high blood levels of glucose, sodium and urea. This syndrome often happens in cats that have concurrent heart or kidney disease. Brain function is affected leading to coma and death).

Cats with diabetes are prone to developing urinary tract infections due to the dilute sugar-rich urine (Mayer-Roenne et al 2007). They may also be more likely to develop heart disease and failure but the cause of this link has not been established (Little & Gettinby 2008).

Treatment of uncomplicated diabetes in cats usually involves injections of insulin every 12 to 24 hours. It is quite common, after starting insulin treatment, for cats to enter a period of remission that lasts from a week to over a year when they do not require insulin treatment (and at this time, become at risk of insulin overdose – see below). This is because the initial insulin treatment relieves the glucotoxicity and enables the surviving insulin-producing cells in the pancreas to increase production and also reduces tissue insulin resistance (Rand 2009). However, the need for insulin treatment usually returns as the underlying disease progresses (Rand 1999).

A major concern in using insulin treatment is the danger of overdosing. The dose needed for effective control of the blood glucose level is only a little lower than the dose that will cause dangerously low blood glucose level. This hypoglycaemia initially shows as weakness and can rapidly progress to brain dysfunction including convulsions, coma and death (Peterson et al 1994).

 

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2.               Intensity of welfare impact

The welfare impacts depend on the severity of the disease - whether it is the uncomplicated form or if it has progressed to the ketoacidosis or hyperosmolar nonketotic diabetes mellitus forms. Affected cats are likely to feel malaise and discomfort associated with reduced appetite, increased thirst, vomiting, diarrhoea and weakness (Peterson et al 1994).

Cats with diabetes require multiple and repeated veterinary procedures. The condition requires interventions for diagnosis and to check for complications such as urinary tract infections. Treatment of the complicated forms of diabetes requires intensive care. This usually lasts only for a few days before the cat either dies or the condition improves to be classed as uncomplicated diabetes.

 

Long-term care of most diabetic cats requires insulin injections. The welfare implication of this varies: some cats tolerate injections easily but many come to resent the procedure and for some the injections become intolerable. Frequent monitoring with blood and urine tests are also required to ensure that appropriate treatment is being used and, again, the welfare impact of these interventions will vary according to their frequency and the character of the cat (Casella et al 2005). Over-treatment with insulin may cause episodes of hypoglycaemia which will cause malaise and may require intensive care.

Many cats with diabetes are euthanased because their owners cannot cope either with the necessary time commitment or the costs (Norsworthy 2003).

 

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3.           Duration of welfare impact

 

Cats with the complicated forms of diabetes mellitus may respond to treatment and recover (to live on for a period with uncomplicated diabetes) or they may die within a few days. The duration of the welfare effects of complicated diabetes mellitus are thus in the order of days or weeks. Cats may live with uncomplicated diabetes mellitus for years depending on the circumstances and response to treatment. Diabetes mellitus reduces life expectancy (Little & Gettinby 2008). It is reported that cats live, on average around 1-2 years with diabetes but this figure excludes those that die soon after diagnosis due to complications and it is common for some cats to survive for many years (Goossens et al 1998, Little & Gettinby 2008).

 

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4.           Number of animals affected

Diabetes mellitus is a common condition in cats. It has been suggested that it affects between 1 in 80 and 1 in 230 cats in the USA and Australia (Rand et al 1997, Baral et al 2003, Prahl et al 2003, McCann et al 2007). The incidence of diabetes may indeed have increased, as earlier reports indicated that it was much less common. Prahl et al (2003) suggested it was seen in around 1 in 1250 cats in 1970. Environmental factors such as activity levels, diet and obesity may be relevant to this change in prevalence but genetic factors may be involved also.

There is evidence that Burmese cats in the UK, Australia and New Zealand are predisposed to the disease (Rand et al 1997, Wade et al 1999, Baral et al 2003, Rand et al 2004). However, this seems not to be the case in the USA population (Panciera et al 1990). This may reflect genetic differences between these populations as there has been little inter-breeding between USA and other populations in recent decades (http://www.fabcats.org/breeders/inherited_disorders/burmese.php).

Burmese cats in Australia are considered to have a roughly 1 in 50 risk of developing diabetes at any age but about 10% of Burmese cats over the age of eight have diabetes (Baral et al 2003). Cats of this breed are affected about four times more than other cats (Rand et al 2004). There are certain family lines in Australia in which about 10% have diabetes (Wade et al 1999).



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5.           Diagnosis

 

Some other diseases have similar signs (eg hyperthyroidism and chronic renal disease) and the diagnosis of diabetes mellitus rests on detection of high levels of glucose in blood and urine. Measurement of fructosamine level may also be useful for diagnosis and monitoring response to treatment (Link & Rand 2008). Diagnosis of the ketoacidotic form depends on detecting ketones in the blood or urine (Zeugswetter et al 2010).

Ancillary diagnostic tests are usually recommended to check for complications of diabetes or concurrent diseases (common in older cats). These include bacterial culture of urine samples as urinary infections are common (Mayer-Roenne et al 2007). Monitoring the treatment of diabetes mellitus is essential. This may involve repeated blood and urine tests. Measurement of the 'glucose curve' to track blood glucose level every 2 hours between insulin injections may be helpful in determining appropriate dose regimes for individuals (Casella et al 2005).

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6.           Genetics

It is known that there is a genetic influence on insulin resistance in cats (Rand et al 2004). Clinical diabetes may be triggered by environmental factors (such as nutrition) in animals that have this genetic predisposition.

The predisposition seen in some Burmese cat populations to diabetes, and the greater prevalence in some family lines, indicate that there is a genetic factor (Wade et al 1999). However, very little is known about this. It has been suggested that the pattern of heredity is not sex linked and that a recessive gene may be involved which may act by affecting tissue sensitivity to insulin (Rand et al 2004).

 

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7.           How do you know if an animal is a carrier or likely to become affected?

There is no genetic test and there is no way to predict which animals are likely to develop diabetes mellitus in later life (except that this appears to be more likely if close relatives are affected). It is not known if the mutant gene or genes can be carried and passed on to offspring by animals that never develop the disease themselves, although this seems quite likely since it thought to be a recessive condition (Wade et al 1999).

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8.          Methods and prospects for elimination of the problem

There are no breeding schemes, as far as we are aware, aimed at reducing the prevalence of diabetes mellitus in Burmese cats. As with other diseases with a suspected genetic influence that has not yet been identified, recommendations for reduction of the number of animals affected by the condition can only be made based on general principles. The disease typically has a late onset, after the age when cats are first bred. Breeding selectively from Burmese cats whose relatives have been free of the disease (and which have good breeding values) is likely to be effective in reducing the number of affected animals (Bell 2010).  Breeding values take account of any available genetic information and the presence or absence of diseases both in the individual and its relatives. Progress in reducing the prevalence of diabetes mellitus in Burmese is likely to be facilitated by greater knowledge of the genetics that underlie the disease.

 

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9.          Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

 

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10.          References

Baral R, Rand JS, Catt M and Farrow H (2003) Prevalence of diabetes mellitus in feline private practice. Journal of Veterinary Internal Medicine 17: 433

Bell JS (2010) Genetic testing and genetic counseling in Pet and Breeding Dogs. 35th World Small Animal Veterinary Association World Congress Proceedings. 2-5th June 2010, Geneva, Switzerland. http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=wsava2010&PID=pr56159&O=VIN accessed 2.11.2011

 

Bennett N, Greco DS, Peterson ME, Kirk C, Mathes M and Fettman M (2006) Comparison of a low carbohydrate – low fibre diet and a moderate carbohydrate – low high fibre diet in the management of feline diabetes mellitus. Journal of Feline Medicine and Surgery 8: 73-84

Casella M, Hassig M and Reusch CE (2005) Home-monitoring of blood glucose in cats with diabetes mellitus: evaluation over a 4-month period. Journal of Feline Medicine and Surgery 7: 163-71

Feldhahn JR, Rand JS and Martin G (1999) Insulin sensitivity in normal and diabetic cats. Journal of Feline Medicine and Surgery 1: 107-15

Forcada Y, German AJ, Noble PJM, Steiner JM, Suchodolski JS, Graham P and Blackwood L (2008) Determination of serum fPLI concentrations in cats with diabetes mellitus. Journal of Feline Medicine & Surgery 10: 480-487

Goossens MM, Nelson RW, Feldman EC and Griffey SM (1998) Response to Insulin Treatment and Survival in 104 Cats with Diabetes Mellitus (1985–1995). Journal of Veterinary Internal Medicine 12: 1–6

Lederer R, Rand JS, Hughes I and Fleeman LM (2003) Chronic or recurring medical problems, dental disease, repeated corticosteroid treatment, and lower physical activity are associated with diabetes in Burmese cats. Journal of Veterinary Internal Medicine 17: 433

Lederer R, Rand JS, Hughes IP, Latter M and Wattle O (2004) Pancreatic Histopathology of Diabetic Burmese and Non-Burmese Cats Abstract from Proceeding of the Annual Meeting of the American College of Veterinary Internal Medicine http://www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2004&PID=pr06369&O=VIN accessed 20.10.2011

Little CJL and Gettinby G (2008) Heart failure is common in diabetic cats: findings from a retrospective case-controlled study in first-opinion practice. Journal of Small Animal Practice 49: 17-25

 

Link RK and Rand JS (2008) Changes in blood glucose concentration are associated with relatively rapid changes in circulating fructosamine concentration. Journal of Feline Medicine and Surgery 10: 583-92

Mayer-Roenne B, Goldstein RE and Erb HN (2007) Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease. Journal of Feline Medicine & Surgery 9: 124-132

McCann TM, Simpson KE, Shaw FJ, Butt JA and Gunn-Moore DA (2007) Feline diabetes mellitus in the UK: the prevalence within an insured cat population and a questionnaire-based putative risk factor analysis. Journal of Feline Medicine and Surgery 9: 289-99

Norsworthy GD (2003) Diabetes mellitus – uncomplicated. In: Norsworthy GD, Crystal MA, Grace SF & Tilley LP (eds) The Feline Patient 2nd edition Lippincott Williams & Wilkins, Baltimore 182-5

Panciera DL, Thomas CB, Eicker SW and Atkins CE (1990) Epizoological patterns of diabetes mellitus in cats 333 cases (1980-1986). Journal of the American Veterinary Medical Association 197: 1504-8

Peterson ME, Randolph JF and Mooney CT (1994) Endocrine diseases. In: Sherding RG (ed) The Cat Diseases and Clinical Management 2nd edition Churchill Livingstone, New York 1465-79

Prahl A, Glickman L, Guptill L, Glickman N and Tentrick M (2003) Time trends and risk factors for diabetes mellitus in cats. Journal of Veterinary Internal Medicine 17: 434

Rand J (1999) Current understanding of feline diabetes: Part 1, pathogenesis. Journal of Feline Medicine & Surgery 1: 143-153

Rand JS (2009) Feline diabetes mellitus In: Bonagura JD and Twedt DC (eds) Kirk’s Current Veterinary Therapy XIV Saunders Elsevier, St Louis 199-204

Rand JS, Fleeman LM, Farrow HA, Appleton DJ and Lederer R (2004) Canine and feline diabetes mellitus: nature or nurture? The Journal of Nutrition supplement 134: 2072S-2080S

Rand JS, Bobbermien LM and Hendrikz JK (1997) Over-representation of Burmese cats with diabetes mellitus. Australian Veterinary Journal 75: 402-5

Reusch CE (2006) Update on feline diabetes mellitus Proceeding of World Small Animal Veterinary Association Congress 2006 http://www.felinediabetes.com/reusch.htm accessed 2.11.2011

Wade C, Gething M and Rand JS (1999) Evidence of a genetic basis for diabetes mellitus in Burmese cats. Journal of Veterinary Internal Medicine 13: 269

Zeugswetter F, Handl S, Iben C and Schwendenwein I (2010) Efficacy of plasma ß-hydroxybutyrate concentration as a marker for diabetes mellitus in acutely sick cats. Journal of Feline Medicine & Surgery 12: 300-305

http://www.fabcats.org/breeders/inherited_disorders/burmese.php accessed 20.10.2011

 

 

 

 

© UFAW 2012

 

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