Feline diabetes mellitus (Proceedings)


Feline diabetes mellitus (Proceedings)

Nov 01, 2010


Diabetes mellitus (DM) can be defined as a group of metabolic diseases characterized by hyperglycemia, which results from defects in insulin secretion, insulin action, or both. DM can occur because of disease affecting the endocrine pancreas and other endocrinopathies such as acromegaly.

Diabetes mellitus in cats is one of the most frequently identified endocrinopathies in cats with incidence rates of 1 in 100 to 1in 400 reported (Panciera et.al. 1990, Rand JS et.al. 1997). Based upon islet histopathology, risk factors, and clinic course of disease, cats seem to develop a form of DM that is most closely related to type-2 DM in humans. Type-1 DM is caused by immune-mediated destruction of beta cells by antibody and T cells, which seems to be a much less common occurrence in cats. Type-2 diabetes is characterized by beta cell dysfunction leading to inadequate insulin secretion and impaired insulin action or insulin resistance.

Insulin resistance is a condition in which a "normal" amount of secreted insulin produces a subnormal response. In an insulin resistant state more insulin has to be secreted to produce the same glucose lowering effect as compared to a "normal" amount. Diabetic cats have been found to be about six times less sensitive to insulin than healthy cats (Feldhahan JR, et.al.1999). In humans there is evidence that inheritance plays a large role in insulin resistance, but it is increased by environmental or lifestyle factors. This is likely similar in cats. In support of there being a genetic bases of disease in cats, in Australia Burmese cats are over-represented accounting for approximately 20% of diabetic cats (Rand JS et.al. 1997). Obesity in cats as in humans seems to play a role in the development of the insulin resistant state. In one study cats that were allowed to become obese demonstrated a 52% decrease in tissue sensitivity to insulin. Also normal weight cats with initial lower insulin sensitivities had a greater risk of developing impaired glucose tolerance as they became obese (Appleton DJ et.al. 2001). Persistent decreased insulin sensitivity/insulin resistance results in hyperglycemia, which in turn leads to excessive production of insulin and beta cell dysfunction and exhaustion. In humans and rats, exercise has been shown to increase insulin sensitivity and lack of exercise impairs insulin action and can add to insulin resistance. Not all cats with DM are or have been obese, however. Diet may also be a factor in the development of DM in cats. Many commercial cat foods contain high levels of highly digestible carbohydrates. Diets high in refined carbohydrates can produce a greater postprandial increase in glucose and insulin secretion. In cats it is thought that these high carbohydrate diets lead to life-long increased demand for insulin secretion and resultant beta cell exhaustion.

Beta-cell dysfunction in humans occurs in stages as beta cell failure progresses: glucose desensitization, beta-cell exhaustion, and glucose toxicity. Some of these stages have been identified in cats. In health insulin secretion occurs in two phases. This first phase is a rapid release of insulin from preformed granules in the beta-cell occurring within a few minutes of ingestion, and the second phase after then first and lasts until normoglycemia is restored. In the affected cat, in response to an intravenous glucose bolus, the first phase of insulin secretion is markedly reduced and the second phase is delayed and exaggerated. As glucose intolerance progresses the second phase of insulin secretion is lost: beta-cell exhaustion. With persistent hyperglycemia glucose toxicity occurs. The mechanism by which glucose toxicity suppresses insulin secretion is unclear. Glucose toxicity leads to irreversible changes that permanently affect the cells ability to produce insulin. The cells with a functional reserve try to compensate and may become hyperfunctioning. It is thought that this increases their susceptibility to glucose toxicity and increases the likelihood of permanent DM (permanent insulin-dependent state). Sulphonylureas, oral hypoglycemic drugs, act by stimulating beta cells to increase insulin secretion and as such may actually increase exhaustion of remaining beta cells. Histopathologic changes seen in glucose toxicity include glycogen deposition and cell death. The degree of severity of glucose toxicity depends on the degree and duration of hyperglycemia (Link KRJ, et.al. 1996).

The most consistent histopathologic finding in cats with DM is islet amyloidosis. More than 80% of diabetic cats have been shown to have islet amyloidosis; although not all cats with islet amyloidosis have DM. Amyloid is derived from the hormone amylin, which is secreted with insulin from beta cells. Amyloid fibrils have been shown to be toxic to beta cells, Amyloid deposition likely contributes to beta cell loss, insulin deficiency, and the progression of DM in cats.

Transient diabetes or diabetic remission is reported to occur 20 up to 84% of adequately treated cats (Feldman and Nelson 2004; Roomp K, et, al. 2009). These cats present with clinical signs and laboratory findings of DM, but clinical signs and blood glucose levels return to normal weeks to a few months after initiating treatment and achieving good diabetic control. Remission may last months to years but may be only weeks in some cats. It is suspected that these cats have subclinical disease and become clinical when illness places extra demands on the pancreas (increased insulin resistance) or when given drugs like glucocorticoids or progesterone or prior to the onset of clinical diabetes. It seems that remission is more likely with early treatment and intensive monitoring to obtain good glycemic control (Roomp K et.al. 2009).