Changes

===Aetiology===

===Aetiology===

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 gluconeogenesis 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:

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 gluconeogenesis 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 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.   

*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 - Dog and Cat|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.   

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.

*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 '''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), [[Hypersomatotrophism - 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 and 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.

*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), [[Hypersomatotrophism - 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 and 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.