Pathology

Diabetes mellitus is a metabolic disorder that comes from the reduction of insulin available for normal function of many cells in the body. The unavailability of insulin can be a result of degenerative changes in Beta cells of the pancreatic islets, reduced effectiveness of the hormone because of the formation of antiinsulin antibodies or inactive complexes, damage to Beta cells from immune-mediated islet cytotoxicity, or inappropriate secretion of hormones by neoplasms in other endocrine organs. The most used classification scheme to human diabetes mellitus is Type 1 and Type 2. Type 1 DM is characterized by a pancreatic Beta-cell autoimmunity, insulin deficiency and disease onset in childhood. On the other hand, the Type 2 DM is associated with obesity and is characterized by insulin resistance and onset during adulthood.

As the canine DM is a disease of insulin deficiency, it is regarded as most similar to human Type 1 DM. The spontaneous cases of diabetes are most likely to occur in mature dogs and in females approximately twice as often as males.

In dogs, the Langerhans islets are often destroyed because of inflammation of the exocrine pancreas. The replacement of both endocrine and exocrine pancreatic cells by fibrous connective tissue due to a chronic relapsing pancreatitis is a frequent cause of diabetes mellitus. In these dogs, the pancreas becomes firm, multinodular, and has scattered areas of hemorrhage and necrosis after a recent relapse (picture 1).

Picture 1. Pancreas of a diabetic dog at necropsy
Department of Veterinary Pathology - UFRGS

In the animal with DM, hepatomegaly occurs as a result of fatty degeneration. The lipids accumulate in the liver as the result of increased lipid mobilization, and the hepatocytes injured by ketonemia have decreased usage of lipids (picture 2).

Picture 2. Necropsy of a dog with diabetes mellitus
Department of Veterinary Pathology - UFRGS

In poorly controlled diabetic dogs, cataracts are often seen. The formation of cataract in the diabetic patient is related to the unique sorbitol pathway by which glucose is metabolized in the lens. Glucose is converted, by the enzyme aldose reductase, to sorbitol and subsequently to fructose by sorbitol dehydrogenase. These sugar alcohols accumulate within the lens and result in an intracellular accumulation of solute and hypertonicity. This accumulation causes a hydropic degeneration of the lenticular fibers. Later, macromolecular aggregation or precipitation of normally translucent lenticular proteins develops, accompanied by disruption of lenticular fibers and formation of interfibrillar clefts. The result is diffuse, often bilateral lens opacity observed in animals with chronic DM (picture 3). 

Picture 3. Cataracts
Department of Veterinary Pathology - UFRGS

Other extra pancreatic lesions found in animals with a poorly controlled DM, such as chronic renal disease, blindness, and gangrene, are the result of microangiophaty characterized by thickening of the capillary basement membrane. These dogs develop nodular or diffuse glomeruloesclerosis (picture 4) characterized by PAS-positive fibrillar deposits of glycoprotein, which occasionally form spherical nodules in the glomerular capillary tufts. Other renal lesions include accumulation of glycogen within cells of the loop of Henle and distal convoluted tubule.

Picture 4. Diffuse glomeruloesclerosis in the kidneys
Department of Veterinary Pathology - UFRGS