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The most common causes of diabetes in cats are obesity, pancreatitis, and most frequently, amyloidosis of the pancreatic beta cells. There appears to be very little gender predisposition to this disease in cats, although it is slightly more common in males than females. As with dogs, the onset of diabetes in cats occurs most often in middle age.

In addition, stress, obesity, and administration of corticosteroids or progestogens may increase the severity of clinical signs.

Diabetes mellitus can be secondary to severe inflammation or neoplasia of exocrine pancreatic tissue, which leads to loss of islet function. In these cases, diabetes is also complicated by exocrine pancreatic insufficiency. Diabetes mellitus can also occur when there is either overproduction of counteracting hormones or insulin resistance. Excessive growth hormone production can be seen in intact, cycling females. Progesterone produced during the luteal phase of the estrous cycle induces the production of growth hormone by the mammary gland, which counteracts the action of insulin.

There are many pathogenic mechanisms responsible for decreased insulin production and secretion, but they are usually related to destruction of islet cells. While dogs tend to develop diabetes mellitus secondary to either immune destruction of the pancreatic beta cells or severe pancreatitis, cats tend to develop diabetes mellitus secondary to pancreatitis or amyloidosis.

Chronic relapsing pancreatitis with progressive loss of both exocrine and endocrine cells and their replacement by fibrous connective tissue results in diabetes mellitus. The pancreas becomes firm and multinodular and often contains scattered areas of hemorrhage and necrosis. As the disease progresses, a thin, fibrous band of tissue near the duodenum and stomach may be all that remains of the pancreas.

Selective infiltration of islets with amyloid, glycogen, and collagen with destruction of islet cells has been reported in diabetic cats. The numbers of beta cells decrease, and the cells become vacuolated. In chronic cases, the islets are difficult to find.

Obesity also predisposes cats to insulin resistance. In obese cats, tissue receptors have decreased insulin sensitivity. This leads to a greater demand for insulin, which can result in exhaustion of the islets of Langerhans.