Pathogenesis of feline diabetes mellitus.

Cats are one of the few species that develop a form of diabetes mellitus that is clinically and histologically analogous to human type 2 diabetes mellitus. Figure 9 summarizes the etiologic factors thought to be involved in the development of feline and human type 2 diabetes. The main metabolic characteristics of type 2 diabetes mellitus are impaired insulin secretion and resistance to the action of insulin in its target tissues. Impaired beta cell function occurs before histologic changes become evident. The characteristic histologic finding in cats with type 2 diabetes is deposition of amyloid in pancreatic islets. Amyloid deposition occurs before the onset of clinical signs, but does not seem to be the primary defect. Pancreatic amyloid is derived form the recently discovered pancreatic hormone amylin. Amylin is synthesized in pancreatic beta cells, and is co-stored and co-secreted with insulin. Amylin has been postulated to be involved in the pathogenesis of feline diabetes mellitus both through its metabolic effects, which include inhibition of insulin secretion and induction of insulin resistance, and via progressive amyloid deposition and beta cell degeneration. Increased amylin concentration has been documented intracellularly in cats with impaired glucose tolerance and in the plasma of diabetic cats, and supports the hypothesis that amylin is involved in the pathogenesis of type 2 diabetes. Obesity is a common finding in diabetic felines and is a contributing factor to the insulin resistance present in type 2 diabetes. Clinical signs of diabetes develop once total insulin secretion decreases to 20% to 25% of normal levels. Many diabetic cats have been treated successfully with oral hypoglycemics, but 50% to 70% of diabetic cats are insulin dependent. Based on histologic evidence, this is the result of extensive amyloid deposition and subsequent beta cell degeneration, rather than autoimmune destruction of pancreatic beta cells associated with type 1 diabetes. Alternative ways of treating type 2 diabetes currently are being investigated. Amylin antagonists recently have been proposed as a novel treatment to reverse the deleterious effects of excessive amylin concentrations. The gastrointestinal hormone glucagon-like peptide-1 may also prove useful in treating diabetic cats, because of its stimulatory effect on insulin secretion and synthesis, and the absence of significant hypoglycemic effect.