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,
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).