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==Introduction==
==Description==
The clinical syndrome described by the term '''diabetes mellitus''' results from intolerance to glucose. It is a chronic disease caused by an absolute or relative deficiency of insulin and, although all body systems are ultimately affected, it is primarily a disorder of carbohydrate metabolism. The approximate incidence of the disease is 13 cases/10,000 dogs years at risk<ref name="one">Fall T, Hamlin HH, Hedhammar A, Kämpe O, Egenvall A. '''Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution.''' ''J Vet Intern Med. 2007 Nov-Dec;21(6):1209-16.''</ref>.
The clinical syndrome described by the term '''diabetes mellitus''' results from intolerance to glucose. It is a chronic disease caused by an absolute or relative deficiency of insulin and, although all body systems are ultimately affected, it is primarily a disorder of carbohydrate metabolism. The approximate incidence of the disease is 13 cases/10,000 dogs years at risk<ref name="one">Fall T, Hamlin HH, Hedhammar A, Kämpe O, Egenvall A. '''Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution.''' ''J Vet Intern Med. 2007 Nov-Dec;21(6):1209-16.''</ref>.
===Aetiology===
===Aetiology===
[[Image:Diabetes Mellitus Type IV hypersensitivity.jpg|right|thumb|150px|Diabetes Mellitus-Brian Catchpole RVC 2008]]
[[Image:Diabetes Mellitus Type IV hypersensitivity.jpg|right|thumb|150px|Diabetes Mellitus-Brian Catchpole RVC 2008]]
[[Insulin]] is produced in the beta cells of the pancreatic islets of Langerhans and is released into the circulation to act on specific cell-surface receptors. Its release is stimulated by rising blood glucose concentration and it is principally insulin which is responsible for the post-prandial cellular glucose uptake and storage observed in humans and dogs. Several hormones (including corticosteroids, progesterone, oestrogen, growth hormone, glucagon and catecholamines) have an antagonistic effect to insulin and cause the blood glucose concentration to increase. Interruptions at any stage in this pathway may produce the clinical syndrome of diabetes mellitus, including:
*Failure to produce insulin resulting in an '''absolute deficiency''' - This may be due to [[Pancreas, Endocrine - Degenerative Pathology|degenerative changes in the beta cells]] or it may occur with severe exocrine pancreatic disease that disrupts the islets of Langerhans. The major example of the latter disease process is [[Pancreatitis|pancreatitis]] and, in cases of this diesase, diabetes mellitus is often found concurrently with [[Exocrine Pancreatic Insufficiency|exocrine pancreatic insufficiency]]. Degeneration of the beta cells, whether it involves the immune system or not, results in '''type 1''' diabetes mellitus and miniature Poodles, Dachshunds and terriers appear to be predisposed to this condition. In humans, it is speculated that immune responses directed at certain pathogens (notably coxsackie virus B1) may cross-react with antigens expressed on the surface of beta cells resulting in immune-mediated destruction of these cells. Whether type 1 diabetes mellitus is associated with a similar misdirected immune response is not yet clear in small animals with several studies giving conflicting results as to the presence of autoantibodies directed at the beta cells at the point at which the disease is first diagnosed. The pathogenesis would be via [[Type IV Hypersensitivity|Type IV hypersensitivity]]. The CTLs react as if all the beta cells in the pancreas are infected by a virus, as it wrongly detects a self antigen presented by the MHC class I on the surface of the cell as foreign. Autoreactive CD8+ CTLs are inadvertently activated, destroying the beta cells, thus preventing the secretion of insulin and causing diabetes type 1 (see diagram).
Cats may suffer from '''islet amyloidosis''' in which the protein amylin is deposited in the tissue and has directly cytotoxic effects on the beta cells. Amylin is a protein which is produced normally in the beta cells at the same rate as insulin and has synergistic effects on many aspects of metabolism. In situations where the synthesis of insulin is increased due to insulin resistance (see below), amylin is also produced in excess and it then forms aggregates that are deposited in the pancreatic tissue.
Cats may suffer from '''islet amyloidosis''' in which the protein amylin is deposited in the tissue and has directly cytotoxic effects on the beta cells. Amylin is a protein which is produced normally in the beta cells at the same rate as insulin and has synergistic effects on many aspects of metabolism. In situations where the synthesis of insulin is increased due to insulin resistance (see below), amylin is also produced in excess and it then forms aggregates that are deposited in the pancreatic tissue.
Reductions in renal output allow ketone bodies and glucose to increase to ever higher concentrations in the blood. Water moves from the intracellular space to compensate for this high plasma osmolality and the alterations in cellular hydration may result in comas or seizures.
Reductions in renal output allow ketone bodies and glucose to increase to ever higher concentrations in the blood. Water moves from the intracellular space to compensate for this high plasma osmolality and the alterations in cellular hydration may result in comas or seizures.
The combined effects of these metabolic derangements may be life-threatening and urgent medical intervention is required.
The combined effects of these metabolic derangements may be life-threatening and urgent medical intervention is required.
'''[[Diabetic Ketoacidosis]]''' provides a complete review of the condition.
====Chronic Disease====
====Chronic Disease====
Diabetic animals may suffer from '''peripheral neuropathies''' and '''retinopathy''' and they will have some level of '''immunosuppression'''. Affected animals are therefore predisposed to the development of chronic skin and urinary tract infections.
Diabetic animals may suffer from '''peripheral neuropathies''' and '''retinopathy''' and they will have some level of '''immunosuppression'''. Affected animals are therefore predisposed to the development of chronic skin and urinary tract infections.
==Signalment==
==Signalment==
Diabetes mellitus is most common in mature dogs and it is twice as common in females than in males. Miniature Poodles, Dachshunds and terriers may suffer from degenerative changes and type 1 disease. Non-insulin dependent diabetes mellitus is paticularly common in obese indoor cats with low physical activity <ref>Slingerland LI, Fazilova VV, Plantinga EA, Kooistra HS, Beynen AC. '''Indoor confinement and physical inactivity rather than the proportion of dry food are risk factors in the development of feline type 2 diabetes mellitus.''' ''Vet J. 2009 Feb;179(2):247-53. Epub 2007 Oct 26.''</ref>.
Diabetes mellitus is most common in mature dogs and it is twice as common in females than in males. Miniature Poodles, Dachshunds and terriers may suffer from degenerative changes and type 1 disease. Non-insulin dependent diabetes mellitus is paticularly common in obese indoor cats with low physical activity <ref>Slingerland LI, Fazilova VV, Plantinga EA, Kooistra HS, Beynen AC. '''Indoor confinement and physical inactivity rather than the proportion of dry food are risk factors in the development of feline type 2 diabetes mellitus.''' ''Vet J. 2009 Feb;179(2):247-53. Epub 2007 Oct 26.''</ref>.
==Diagnosis==
==Diagnosis==
An '''electrocardiogram''' should be performed in cases of DKA to assess the degree of cardiac compromise caused by hyperkalaemia. Common findings in this condition include bradycardia, reduced R wave amplitude, reduced or absent P waves, spiked T waves, a reduced Q-T interval and an increased P-R interval.
An '''electrocardiogram''' should be performed in cases of DKA to assess the degree of cardiac compromise caused by hyperkalaemia. Common findings in this condition include bradycardia, reduced R wave amplitude, reduced or absent P waves, spiked T waves, a reduced Q-T interval and an increased P-R interval.
==Treatment==
==Treatment==
Animals presenting with DKA are often collapsed, comatose and severely dehydrated. Stabilisation would involve the following aspects of care:
Animals presenting with DKA are often collapsed, comatose and severely dehydrated. Stabilisation would involve the following aspects of care:
*'''Intra-venous fluid therapy''' with a suitable product. The priorities of fluid therapy are to hydrate the animal and prevent further damage due to poor tissue perfusion and to provide sodium which will have been lost with the osmotic diuresis. With the latter aim in mind, 0.9% sodium chloride solution is recommended. Other clinicians prefer to use compound sodium lactate (Hartmann's solution) as it provides some buffering capacity and, because its potassium content is much lower than that of normal plasma, it is unlikely to worsen any hyperkalaemia. Fluid deficits should be replaced over 24 hours and fluids should not be infused at rates much above twice maintenance to prevent cerebral oedema for occurring due to rapid alterations in electrolyte concentrations. It would also be advisable to measure serum electrolyte concentrations regularly to prevent this effect from occurring.
*'''Intra-venous fluid therapy''' with a suitable product. The priorities of fluid therapy are to hydrate the animal and prevent further damage due to poor tissue perfusion and to provide sodium which will have been lost with the osmotic diuresis. With the latter aim in mind, 0.9% sodium chloride solution is recommended. Other clinicians prefer to use compound sodium lactate (Hartmann's solution) as it provides some buffering capacity and, because its potassium content is much lower than that of normal plasma, it is unlikely to worsen any hyperkalaemia. Fluid deficits should be replaced over 24 hours and fluids should not be infused at rates much above twice maintenance to prevent cerebral oedema for occurring due to rapid alterations in electrolyte concentrations. It would also be advisable to measure serum electrolyte concentrations regularly to prevent this effect from occurring.
*'''Insulin''' should be provided to reverse the metabolic changes that have resulted in the crisis. Since the administration of insulin may also have marked consequences for electrolyte status, it is best to administer it gradually as an infusion of soluble insulin. The insulin solution (made up in 0.9% sodium chloride) should be administered through a separate fluid line to that used for conventional fluids and the solution should be run through this line to saturate the bindings sites along the plastic with insulin molecules. Blood glucose concentration should be measured every regularly. Alternatively, intermittent injections of insulin may be used at hourly intervals while also measuring the blood glucose concentration.
*'''Insulin''' should be provided to reverse the metabolic changes that have resulted in the crisis. Since the administration of insulin may also have marked consequences for electrolyte status, it is best to administer it gradually as an infusion of soluble insulin. The insulin solution (made up in 0.9% sodium chloride) should be administered through a separate fluid line to that used for conventional fluids and the solution should be run through this line to saturate the bindings sites along the plastic with insulin molecules. Blood glucose concentration should be measured regularly. Alternatively, intermittent injections of insulin may be used at hourly intervals while also measuring the blood glucose concentration.
It is important that insulin is not administered too quickly because it causes both potassium and phosphate to move intracellularly with glucose. This can result in rebound hypoglycaemia, hypokalaemia, hypophosphataemia and hypomagnesaemia because the total body levels of these cations will probably have been reduced by the enforced osmotic diuresis). Severe hypophosphataemia may result in the development of haemolytic anaemia. Potassium may need to be supplemented from the outset and the rate at which insulin is administered should be reduced if the animal is hypokalaemic on presentation. Other electrolytes should only be supplemented after their serum levels have been measured.
It is important that insulin is not administered too quickly because it causes both potassium and phosphate to move intracellularly with glucose. This can result in rebound hypoglycaemia, hypokalaemia, hypophosphataemia and hypomagnesaemia because the total body levels of these cations will probably have been reduced by the enforced osmotic diuresis). Severe hypophosphataemia may result in the development of haemolytic anaemia. Potassium may need to be supplemented from the outset and the rate at which insulin is administered should be reduced if the animal is hypokalaemic on presentation. Other electrolytes should only be supplemented after their serum levels have been measured.
*'''Infections''' occur frequently, either as a cause or effect of DKA. Broad spectrum bactericidal antibiotics are generally recommended in all cases.
*'''Infections''' occur frequently, either as a cause or effect of DKA. Broad spectrum bactericidal antibiotics are generally recommended in all cases.
==Prognosis==
==Prognosis==
The overall prognosis for animals with diabetes mellitus is dependent on multiple factors but the '''median survival time from diagnosis is two years in dogs''' with a relatively higher mortality in the six months following diagnosis<ref name="one">Fall T, Hamlin HH, Hedhammar A, Kämpe O, Egenvall A. '''Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution.''' ''J Vet Intern Med. 2007 Nov-Dec;21(6):1209-16.''</ref>. The quality of life of animals with diabetes mellitus should be monitored by both owners and veterinary surgeons.
The overall prognosis for animals with diabetes mellitus is dependent on multiple factors but the '''median survival time from diagnosis is two years in dogs''' with a relatively higher mortality in the six months following diagnosis<ref name="one">Fall T, Hamlin HH, Hedhammar A, Kämpe O, Egenvall A. '''Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution.''' ''J Vet Intern Med. 2007 Nov-Dec;21(6):1209-16.''</ref>. The quality of life of animals with diabetes mellitus should be monitored by both owners and veterinary surgeons.
{{Learning
|flashcards = [[Small Animal Abdominal and Metabolic Disorders Q&A 06]]<br>[[Feline Medicine Q&A 15]]
|powerpoints = [[E-Lecture:Canine Diabetes|Canine Diabetes e-lecture]]
|literature search = [http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Diabetes+Mellitus%22&occuring1=title&rowId=2&options2=AND&q2=&occuring2=freetext&rowId=3&options3=AND&q3=&occuring3=freetext&publishedstart=2000&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all&x=54&y=14 Diabetes mellitus publications since 2000]
[http://www.cabdirect.org/search.html?rowId=1&options1=AND&q1=%22Diabetes+Mellitus%22&occuring1=title&rowId=2&options2=AND&q2=dogs&occuring2=od&rowId=3&options3=AND&q3=&occuring3=freetext&x=38&y=9&publishedstart=&publishedend=yyyy&calendarInput=yyyy-mm-dd&la=any&it=any&show=all Diabetes mellitus in dogs publications]
[http://www.cabdirect.org/search.html?q=title%3A%28%22Diabetes+Mellitus%22%29+AND+od%3A%28cats%29 Diabetes mellitus in cats publications]
|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2009/20093017995.pdf ''' Diabetes in cats that require immunosuppressive therapy.''' Schermerhorn, T.; Gething, M.; Jones, B.; Australian Small Animal Veterinary Association, Bondi, Australia, 33rd World Small Animal Veterinary Association Congress, Dublin, Ireland, 20-24 August 2008, 2008, pp 457-458, 5 ref.]
[http://www.cabi.org/cabdirect/FullTextPDF/2007/20073161530.pdf '''Diabetes mellitus in dogs - long term management.''' Kshama, M. A.; Deepti, B. R.; Sudha, G.; Intas Pharmaceuticals Ltd, Ahmedabad, India, Intas Polivet, 2007, 8, 1, pp 117-120, 5 ref.]
[http://www.cabi.org/cabdirect/FullTextPDF/2006/20063240193.pdf '''Recent advances in diabetes mellitus.''' Schermerhorn, T.; The North American Veterinary Conference, Gainesville, USA, The North American Veterinary Conference 2003, Small Animal and Exotics. Orlando, Florida, USA, 18-22 January, 2003, 2003, pp 310-312]
[http://www.cabi.org/cabdirect/FullTextPDF/2005/20053195425.pdf ''' Management of the complicated diabetic.''' Zoran, D. L.; Eastern States Veterinary Association, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Volume 19, Orlando, Florida, USA, 8-12 January, 2005, 2005, pp 329-331, 4 ref.]
|Vetstream = [https://www.vetstream.com/felis/Content/Disease/dis00139.asp Diabetes mellitus]
}}
==References==
==References==
[[Category:Cell Mediated Autoimmune Diseases]][[Category:To Do - Blood]]
{{review}}
[[Category:Liver_-_Degenerative_Pathology]][[Category:Cat]][[Category:Dog]]
[[Category:To_Do_-_James]]
{{OpenPages}}
[[Category:Liver_-_Degenerative_Pathology]][[Category:Pancreatic Diseases - Cat]][[Category:Endocrine Diseases - Cat]][[Category:Neurological Diseases - Cat]][[Category:Immunological Diseases - Cat]][[Category:Liver Diseases - Cat]][[Category:Liver Diseases - Dog]][[Category:Pancreatic Diseases - Dog]][[Category:Endocrine Diseases - Dog]][[Category:Neurological Diseases - Dog]][[Category:Immunological Diseases - Dog]]
[[Category:Cell Mediated Autoimmune Diseases]][[Category:Endocrine System - Pathology]]
[[Category:Expert_Review]]
[[Category:Expert_Review]]