Diabetes mellitus in dogs (Proceedings)


The endocrine pancreas is comprised of groups of cells (islets of Langerhans) scattered throughout the acinar parenchyma of the gland in a ratio of approximately 90% acinar cells (exocrine function) to 10% of islet cells (endocrine function). The pancreas is a boomerang-shaped organ comprised of two "wings" (duodenal and omental) in the cranial right quadrant of the abdomen.

The endocrine pancreas is comprised of groups of cells (islets of Langerhans) scattered throughout the acinar parenchyma of the gland in a ratio of approximately 90% acinar cells (exocrine function) to 10% of islet cells (endocrine function). The pancreas is a boomerang-shaped organ comprised of two "wings" (duodenal and omental) in the cranial right quadrant of the abdomen.

The islets contain 4 types of cells which synthesize different hormones. The most numerous cells are the beta cells which produce insulin. The alpha cells produce glucagons; the D cells produce somatostatin and the PP cells produce pancreatic polypeptide. The venous drainage from the pancreas is via the hepatic portal vein, thus the liver is the recipient of the major physiologic effects of these hormones.

Normal physiology

After a meal, glucose and other nutrients are absorbed from the GI tract and into the circulation. During this process, insulin is secreted by the beta cells of the pancreas. Other stimuli of insulin secretion include: increased concentration of amino acids and GI hormones During this phase insulin produces the movement of glucose into the target cells (via insulin-specific receptors) for metabolism of energy and storage of glycogen and fat. The net physiologic effect of insulin is to lower blood glucose, store fat into adipose tissue and synthesize proteins. Simultaneously, glucagon is secreted by the alpha islet cells in response to increased amino acid concentration. Glucagon is a potent insulin antagonist, by stimulating glucogenolysis and gluconeogenesis, with a net effect being an increase in blood glucose concentration. This bi-hormonal effect of both insulin and glucagons prevents hypoglycemia when a dog or cat ingests a meal that is high in protein and low in carbohydrate.

This increase in blood glucose concentration produces a negative feedback effect upon the pancreatic alpha cells shutting off further secretion of glucagon. Insulin is required for the glucose to enter the alpha islet cells in order to inhibit glucagons secretion. This explains why glucagons levels are elevated in diabetic cats and dogs that have and absolute insulin deficiency despite elevated glucose levels. (the "bi-hormonal" hypothesis of diabetes mellitus).

Several hours after eating, during the post-absorptive state, there is a drop blood glucose concentration, causing a reduction in insulin and increase in glucagon secretion. The glucagon stimulates gluconeogenesis with subsequent increase in blood glucose, in order to maintain it in a normal range. The major stimulus for the glucagons secretion is hypoglycemia.

Insulin is the most important hormone that stimulates free fatty acid (FFA) storage in adipose tissue. During prolonged periods of starvation or uncontrolled diabetes mellitus FFA's are mobilized because blood insulin levels are reduced and glucagon levels are increased.

Glucose is the primary source of energy in nervous tissue which can only store glycogen for a few minutes, thus it is essential that blood be maintained in the normal range. If moderate to severe hypoglycemia occurs glucagons and epinephrine are secreted rapidly (the amount of secretion depends upon the rate and magnitude of hypoglycemia). Epinephrine will inhibit insulin secretionand stimulate glycogenolysis which increases blood glucose. In addition STH and glucocorticoids are secreted approximately 30 minutes after glucagon and epinephrine and will inhibit glucose utilization and stimulate gluconeogenesis. These physiologic events are vital to maintain normoglycemia in the brain.

Diabetes mellitus

This common endocrinopathy results from a relative or absolute deficiency of insulin and overproduction of glucagon, resulting in persistent hyperglycemia. Nearly 100% of affected dogs and 50-70% of affected cats are insulin dependent. Its incidence is 2 out of 1000 dogs seen every year and is more common in females (approximately 75% of all cases). Castrated male dogs are at a greater risk than intact male dogs. Diabetes mellitus can occur at any age (< 1 year yo 15 years) but thr peak ages of incidence are 7 to 11 years. The commonly breeds affected include: poodles, dachshunds, keeshounds, cairn terriers, miniature schnauzers, schipperkes, miniature pinschers and English springer spaniels. Breeds that are at a reduced risk to develop diabetes mellitus include: collies, German Shepherds, boxers, Pekinese and cocker spaniels.


Most dogs with diabetes mellitus have Type 1 or insulin-dependent diabeles mellitus (IDDM), as a result of beta islet cell destruction, hypothesized to be an immune-mediated process. IDDM probably depends upon the combination of genetic susceptibility, environmental (pollutants, infection-pancreatitis), followed by persistent immune destruction of the beta islet cells, resulting in severe insulin deficiency, combined with other hormonal factors (hyperglucagonemia, hyperadrenocorticism, excess STH release- increasing insulin resistance).

On the other hand, many feline diabetics can display the feline equivalent of human Type 2 or adult-onset, usually non-insulin dependent diabetes mellitus (NIDDM). Type 2 diabetes mellitus develops from insulin resistance combined with abnormal insulin secretion. Histologically the islet cells of many diabetic cats contain amyloid deposition (similar to humans). Usually the disease is diagnosed much later in its course than its canine counterpart, beta cell function has greatly compromised and approximately 60% of affected cats wind up requiring insulin therapy. Other endocrine disorders can lead to severe insulin resistance in the cat and eventual diabetes mellitus (hyperadrenocorticism-90% of affected cats are diabetic and megesterol therapy-progestin-induced hypersomatotropism).

The relative or absolute deficiency of insulin results in hyperglycemia, because insulin is needed to transport glucose into the tissues. In order to produce cellular energy glcogenolysis and gluconeogenesis are greatly accelerated. Because glucose cannot be transported into the pancreatic alpha cells to inhibit further glucagon secretion, a hyperglucagonemia exists, worsening the hyperglycemia. Furthermore, the lack of the anabolic effect on protein, as the result of insulin deficiency results in an accelerated release of amino acids by the tissues, causing further gluconeogenesis. Tissues that require insulin transport for glucose begin to utilize FFA for energy (these are mobilized due to insulin deficiency which is instrumental in the deposition of FFA into adipose tissue). Although some tissues can directly utilize FFA for energy, the vast majority of FFA enter the liver and are synthesized to ketoacids. If the rate of ketone production exceeds the metabolism, acidosis develops. Combining the hyperglycemia (canine real threshold~ 180 mg/dl) and ketonuria results in an intense osmotic diuresis The osmotic diuresis often results in severe hypokalemia, hyponatremia and dehydration.

Due to the total catabolic effect upon the body, the hypothalamic satiety center fails to respond to the hyperglycemia and polyphagia may develop. Inspite of the excellent appetite, the lack of insulin activity results in a severe catabolic state and weight loss. ("Famine in the midst of plenty").

In order for the severly ill patient that develops profound DKA (diabetic ketoacidosis), STH, glucagon and cortisol usually must play a significant role. Because affected dogs and cats are usually elderly, complicating conditions may be present (UTI, sepsis, hyperadrenocrticism, renal failure/hypertension, pyometra, IBD, neoplasia and cardiovascular disease, hyperthyroidism in cats). Anorexia and vomition in DKA can lead to further dehydration, hypokalemia, pre-renal azotemia and further weakness my be part of the clinical picture. Elevations in the BUN, glucose and dehydration often result in severe hyperosmolality.

Clinical signs

In uncomplicated diadetic dogs and cats the most frequent signs are PU/PD, weight loss despite polyphgia. Dogs may also be presented because of the rapid onset of cataracts (few days~50% of cases). Some patients may appear to be obese but there is marked muscle-wasting; other patients (~50%) are cachectic. Most affected dogs and cats have palpable hepatomegaly upon physical examination. Approximately 10% of cats develop diabetic neuropathy with weakness in the hindquarters and typical plantigrade posture Affected cats have a dull, unkempt haircoat; while approximately 40% of dogs may exhibit seborrhea, pyoderma, hyperkeratosis and patchy alopecia. Although 80% of dogs and 50% of cats may exhibit ketonuria, severe DKA is not present unless, severe vomition, anorexia, dehydration and occasionally shock-like signs occur. Approximately 15% of dogs and one-third of cats may exhibit jaundice in DKA. Other signs may include hypo/hyperthermia abdominal pain and diarrhea.


The diagnosis of uncomplicated diabetes mellitus includes moderate to severe persistent fasting hyperglycemia (>300 mg/dl), glycosuria, accompanied by the salient clinical signs Because cats often have hyperglycemia ( ~250 mg/dl) due to stress (long car ride, just leaving the house if they are indoor cats, waiting in a crowded noisy waiting room, venipuncture/restraint etc.), the clinician should definitely pursue a history of PU/PD, weight loss and weight loss despite polyphagia. A CBC, biochemical profile, urinalysis/culture via cystocentesis and radiographs of thorax/abdomen should be part of the initial data base to document concurrent diseases. Fasting lipemia is frequently encountered in dogs (50%) and hypercholesterolemia is found in >80% of cats and >60% of dogs Liver enzyme. elevations (ALT, SAP, bilrubin-cats) are common in diabetic patients, especially if DKA is present. Patients with DKA have laboratory evidence of metabolic acidosis ( subnormal CO2, HCO3 and pH levels) and pre-renal azotemia (elevations of BUN and creatinine with a urine SG>1.025). Severely ill diabetic dogs and cats will exhibit hyperosmolality (>350 mOsm/kg)


Management of the diabetic dog or cat is usually a rewarding experience for the clinician. Occasionally, treatment of affected patients is wrought with complications and frustration. In the uncomplicated diabetic dog, the clinician must realize that the tight glycemic controls mandatory for humans is not overly necessary in dogs. Firstly, dogs don't live as long as humans and the catastrophic complications seen in poorly regulated human diabetics are rarely encountered in dogs (microangiopathy of the retina and glomerulus, atherosclerosis, gangrene etc.). For the dog that is still eating and drinking, intensive therapy and hospitalization is not necessary. The treatment of choice for such patients is porcine lente insulin. This agent has been available in the UK and Europe for nearly a decade (Caninsulin, Intervet) and is finally available in the USA (Vetsulin U-40, Intervet). The theory behind the preference of using pork derived insulin in the canine is that that the amino acid sequence for insulin in both species are identical, thus the chances for the development of ant-insulin antibodies and insulin "allergies" should be minimized (this may be more hypothetical than practical). Lente is a type of insulin that is intermediate in onset and duration (onset of effect-30 min.-2hrs., peak effect-2-10 hrs. and duration-8-20 hrs.). It is administered subcutaneously. When originally approved for use in the dog, Vetsulin was touted as a sid. treatment for canine diabetes mellitus, however in this author's experience many dogs require bid therapy. In addition, Vetsulin is available as a U-40 concentration, however human pharmacies don't carry U-40 syringes. This author prefers to initiate insulin therapy at a dosage of 0.25IU/kg bid to minimize the possibility of the Somogyi effect (rebound hyperglycemia as a result of excessive insulin dosage due to compensatory release of GH, cortisol and epinephrine). Other important therapeutic steps in the management of a non-complicated canine diabetic include: 1) dietary therapy ( a high fiber, low carbohydrate, low fat and relatively high protein diet is effective), 2) weight reduction (obesity results in abnormal glucose tolerance-the high fiber, low calorie diet mentioned above should be beneficial) and 3) exercise (it is obvious that exercise and diet will result in weight loss which will improve the insulin's effectiveness on the cellular receptors).The patient should be fed on a consistent daily basis with 50% of the total caloric intake fed just prior to the am insulin dosage and the remaining 50% fed just prior to the pm insulin administration. Exercise should be gradual and consistent on a daily basis and not overly strenuous (which may produce hypoglycemia). At release, the pet owner should be thoroughly educated about the administration of insulin, how long the insulin remains effective when stored in a refrigerator (approximately 1 month for Vetsulin) and the signs of hypoglycemia (rear leg weakness, irritability, lethargy, tremors, convulsions and coma). The owner should instructed to have source of readily-available sugar (honey or syrup) in case any of the above symptoms become apparent. The diabetic dog should be rechecked approximately 1 week after the initial diagnosis is made and the commencement of insulin therapy. The owner should be questioned about the dog's water intake, urine output and overall health status. A 10 hour serial blood glucose curve is constructed (dog is fed and given insulin at home and a blood glucose level is checked q2h for 5 readings). If the blood glucose curve reveals hyperglycemia (never getting <200 mg/dl during the day), the insulin dose is gradually increased (1-5 units/injection, depending on the severity of the hyperglycemia and the size of the dog). During the first month of insulin regulation, this author prefers to recheck the patient on a weekly basis and perform glucose curves. The dog is considered to be well-regulated when the PU/PD has ceased, weight loss is progressing to a stable value and the dog is enjoying its exercise routine.

Another valuable indicator of glycemic control includes the serum fructosamine level. Fructosamines are glycated proteins which are produced as a result of an irreversible non-enzymatic, insulin-independent binding of glucose to serum proteins and are an indicator of the mean glucose concentration during the biological lifespan of the protein ( 1-3 weeks depending upon the protein ). The degree of glcosylation of the serum proteins is proportional to the blood glucose concentration. Thus, dogs with a higher average blood glucose over the 1-3 week period will have a higher serum fructosamine level. The opposite is true for diabetic dogs with a lower fructosamine level. Serum fructosamine levels give the clinician information about the dog's glycemic control over an extended period of time and are not affected by acute factors which could elevate blood glucose level (stress, excitability etc.). This author prefers to run a serum fructosamine level at 6-8 weeks after commencement of insulin therapy and then 2-4 times/year.

Once the dog is well-regulated and is an intact female, ovariohystecctomy should be performed prior to the next estrus cycle which could greatly increase insulin requirements due to the increased concentrations of estrogens and progestins (which will stimulate the release of GH, a powerful insulin antagonist).


Drazner, FH: Small Animal Endocrinology Churchill Livingstone. 1984.

Drazner, FH: A Case Report of a Dog with Gastrinoma, Resembling the Zollinger-Ellison Syndrome. California Veterinarian. 1978.

Mooney, CT. and Peterson ME (eds) BSAVA Manual of Canine and Feline Endocrinology. BSAVA. 2004.

Monroe, WE: Disease of the Endocrine Pancreas and Pituitary Gland in: Leib MS.and Monroe WE.:(eds.) Practical Small Animal Internal Medicine, WB Saunders. 1997.

Related Videos
dvm360 Live! with Dr. Adam Christman
dvm360 Live! with Dr. Adam Christman
dvm360 Live! with Dr. Adam Christman
© 2023 MJH Life Sciences

All rights reserved.