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==Description==
==Description==
The clinical syndrome described by 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.
*Occurs in most species, most commonly in dog and cat
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. 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:
*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 after severe exocrine pancreatic disease that also disrupts the islets of Langerhans. The major example of the latter disease is pancreatitis and diabetes mellitus is often found 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.
*Presence of '''specific antibodies''' in the blood that reduce the effective concentration of insulin - This is a form of immune-mediated disease that has no apparent initiating factor.
*Presence of high concentrations of '''hormones that are antagonistic to insulin''' - This occurs with many endocrine diseases that result in elevated levels of particular hormones. Examples include [[Canine Hyperadrenocorticism - Cushing's Disease|hyperadrenocorticism]] (due to corticosteroids), [[Acromegaly|acromegaly]] (due to growth hormone) and phaeochromocytoma (due to catecholamines). Pregnancy is maintained by high blood concentrations of progesterone in small animals and this may cause '''gestational''' or type 3 diabetes. A similar phenomenon may occur during dioestrus. Iatrogenic diabetes mellitus may be induced when high doses of corticosteroids or megoestrol acetate (a synthetic progestagen) are administered. Even when the antagonisitic factor is withdrawn, the signs may remain if the islets of Langerhans are in a state of '''islet cell exhaustion''', a form of degeneration that results from chronic hyperstimulation.
*Failure of peripheral tissues to respond to insulin, resulting in '''resistance''' - This is the cause of '''type 2''' diabetes mellitus which is described most commonly in obese cats. As above, chronic hyperstimulation of the beta cells may result in islet cell exhaustion and insulin insufficiency.
*Other factors are likely to be involved in the aetiopathogenesis of the disease, including stress, infection and genetic factors.
The deficiency or insufficiency of insulin means that peripheral tissues are not able to utilise glucose as an energetic substrate.
==Signalment==
*Predisposed to [[Pancreas - Inflammatory Pathology|pancreatitis]] and may also have [[Exocrine Pancreatic Insufficiency|pancreatic insufficiency]]
*Predisposed to [[Pancreas - Inflammatory Pathology|pancreatitis]] and may also have [[Exocrine Pancreatic Insufficiency|pancreatic insufficiency]]
*Persistent [[Glucagonoma|increase in glucagon]] may cause hyperglycaemia
*Persistent [[Glucagonoma|increase in glucagon]] may cause hyperglycaemia
*More common in mature dogs, twice as common in females than in males
*More common in mature dogs, twice as common in females than in males
==Diagnosis==
==Diagnosis==
The diagnosis of diabetes mellitus may be challenging, especially in collapsed animals presenting with diabetic ketoacidosis.
===Clinical signs===
===Clinical signs===
The following signs are common in unstabilised dogs and cats with type 1 diabetes mellitus:
*Polyuria
*'''Polyuria''' and '''polydipsia''' because the blood glucose concentration excedes the renal threshold for reabsorption in the proximal convoluted tubules.
*Polydypsia
*'''Polyphagia''' in the face of '''weight loss''' because peripheral tissues are not able to utilise blood glucose and body reserves of carbohydrate, fat and protein are degraded to meet the metabolic energy requirement. This pair of clinical signs are sometimes romantically described as resembling 'starvation in the face of plenty'.
*'''Muscle wasting''' occurs in advanced cases when body protein reserves are mobilised.
*'''Hepatomegaly''' results from increased storage of glucose as glycogen in hepatocytes. Individual hepatocytes shown signs of hydropic change or 'cloudy swelling' as they accrue increasing amounts of glycogen.
*Muscle wasting (but some animals may present obese)
*'''Cataracts''' develop as the metabolism of the lens is altered to compensate for hypergycaemia. Glucose is usually degraded to water and carbon dioxide via the conventional Ebden-Meyerhoff pathway but, when this pathway is saturated, it is also converted to fructose and sorbitol by the enzyme system aldose reductase. This sorbitol and fructose leave the lens slowly and their presence leads to the osmotic movement of water into the lens, producing a cataract.
*Hepatomegaly
Older cats may present with type II diabetes mellitus and these animals are often '''obese'''.
*Cataracts (dogs)
Animals with unstable diabetes mellitus may progress into diabetic ketoacidosis, a state that requires emergency treatment. Such animals often show:
**Dehydration
*'''Dehydration'''
**Depression
*'''Depression''' and coma
**Inappetance
*'''Inappetance'''
**Vomiting
*'''Vomiting''' and diarrhoea
**Diarrhoea
*'''Ketotic breath'''
Many of these clinical signs are underlain by the reduced cardiac output that occurs with DKA due to the renal loss of water and sodium. Blood pressure and peripheral perfusion are therefore reduced, leading to eventual circulatory collapse, coma and death
===Diagnostic Imaging===
===Diagnostic Imaging===