Diabetes Mellitus (DM) in Dogs

Diabetes Mellitus (DM) in dogs classified as either type I or type II, is a generally treatable condition caused by insulin deficiency.

At diagnosis, most diabetic dogs are suspected of having type I:

• Type I patients, characterized by permanent inability to produce insulin, often require exogenous insulin administration.
• Diabetes Mellitus has a potential immune-mediated cause (though this is not firmly established).
• Diabetogenic drugs, pregnancy, and chronic pancreatitis are also possible causes of canine diabetes mellitus.

Etiology

Diabetes Mellitus (DM) in dogs is caused by β-cell of pancreas. The cause of β-cell loss is likely multifactorial: autoimmunity, genetics, environment, and diseases resulting in insulin antagonism.

Risk Factors

• Some breeds are at higher risk for diabetes, (eg, Australian terriers, Samoyeds, Keeshonds) while others appear resistant to its development
• Females are at increased risk, regardless of neuter status.
• Neutered males are at greater risk than intact males.
• Previous hyperadrenocorticism
• Obesity
• Inactivity
• Cushing’s disease and diabetes mellitus may exist as co-morbidities
• Most dogs are diagnosed >8 years of age. The large age range may reflect different genetic susceptibilities to diabetes mellitus, drug exposures, or presence of disease resulting in insulin antagonism.

Pathophysiology

Insulin deficiency results in hyperglycemia by causing:

• Uninhibited hepatic glucose production.
• Impaired entry of glucose into tissues.
• Accelerated protein and lipid catabolism.

Persistent hyperglycemia results in glucosuria when the renal tubular threshold for glucose excretion >180–220 mg/dL.

• Increased proteolysis leads to muscle wasting and poor wound healing.
• As the accelerated lipid catabolism persists, hepatic lipidosis develops and ketoacidosis can result secondary to enhanced ketone body production.
• Endothelial damage and immunosuppression ultimately occur.

System Involved

• As an immunosuppressive disorder, diabetes mellitus can affect many systems; urinary tract and kidney infections, and other bacterial infections may result.
• Because of chronic hyperglycemia, uncontrolled diabetes mellitus can result in cataracts.

Clinical Signs

• Polyuria, Polydipsia (PuPd)
• Polyphagia
• Weight loss
• Owners occasionally report acute blindness secondary to cataract formation.
• There are no classic findings in nonketotic or healthy diabetic dogs.
• While many diabetes mellitus patients are overweight, others may be thin and muscle wasted.
• Some have cataracts and anterior uveitis on ocular examination.

Diabetic neuropathy

• It is less commonly seen in dogs than in cats.
• Furthermore, clinical signs in dogs differ from those in cats.
• Primary clinical findings in cats are plantigrade posturing, subtle muscular weakness, neurologic deficits, and muscle atrophy; those in dogs include chronic and progressive hindlimb weakness that can also involve the forelimbs.
• This degree of weakness varies from mild paraparesis to more severe involvement with tetraparesis and tetraplegia
• Other signs include knuckling, hyporeflexia, muscle atrophy, and weakness.

Diagnosis

• Diagnosis is based on signs and history, as well as documentation of persistent hyperglycemia and glucosuria.
• Stress hyperglycemia may occur in hyper-excitable dogs.
• Lower frequency than cats.
• If diabetes mellitus is suspected, measurement of serum fructosamine should be considered.

Laboratory Findings & Imaging

There is no consistent pattern of laboratory or imaging abnormalities among diabetic dogs. Findings depend on patient, disease severity, and comorbidities.

Common laboratory abnormalities are a direct result of insulin deficiency

• Hyperglycemia
• Hypertriglyceridemia
• ALP and ALT elevations
• Less common abnormalities are not consistently observed and may reflect co-morbid conditions.
• Hematologic and biochemical changes may include mild anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, hyperketonemia, and mild increases in serum ALT and ALP.
• If dealing with a DKA patient, electrolyte abnormalities, azotemia, and/or acidosis may also be noted on the biochemistry panel.
• Ketonuria and evidence of urinary tract disease (pyuria, hematuria, bacteriuria) may be present on urinalysis.
• Abdominal imaging may reveal nonspecific hepatic changes.
• Evidence for concurrent diseases (eg, pancreatitis, renal failure) may be detected with abdominal imaging.

Differential Diagnosis

• Hyperadrenocorticism (HAC) is the most common differential for diabetes mellitus.
• Chronic kidney disease, a common cause of polyuria, polydipsia, and weight loss, is seldom associated with hyperglycemia or glucosuria.
• Pheochromocytoma and pancreatitis infrequently cause hyperglycemia, polyuria, and polydipsia.

Treatment

Intermediate and long-acting insulins are used for long-term management of diabetes mellitus (DM).

• Intermediate-Acting Insulin
  • Neutral protamine Hagedorn (NPH)
  • Purified porcine insulin zinc
  • Protamine zinc insulin (PZIR)
• Longer-Acting Insulins
  • Glargine insulin
  • Detemir insulin

Administration

• All intermediate acting insulins should be started at a dose of 0.5 U/kg q12h.
• Longer-acting insulins should also be started at 0.5 U/kg.

Dogs almost always require twice-daily insulin. Some cats receiving longer-acting insulins may be treated effectively with once-daily injections, but most cats require twice-daily injections, even when treated with longer-acting insulins.

Contraindications & Precautions

Insulin can cause hypoglycemia if the dose is too high, a cat or dog has transient diabetes mellitus and no longer requires insulin, the patient did not eat its entire meal but received a full dose of insulin, or the patient exercised excessively without gradual adjustment of diet and insulin.

Glipizide

The sulfonylurea glipizide, which stimulates insulin secretion from pancreatic beta cells, is the oral hypoglycemic most studied in diabetic cats. Potential side effects of glipizide include vomiting shortly after administration, hypoglycemia, increased serum hepatic enzyme activities, and icterus.

• 2.5mg per cat PO q12h for 2 weeks
• If adverse side effects are not observed by the end of 2 weeks and the cat is still hyperglycemic, the dose is increased to 5 mg/cat PO q12h.
• If blood glucose concentration remains above 300 to 400 mg/dL after 4 weeks, treatment is discontinued and insulin is administered.

Additional Treatment

Activity

• Exercise promotes weight loss in obese patients and increases glucose transport and glycogen synthesis.
• Moderate consistent exercise is recommended at fixed times and patients should be conditioned to exercise gradually.
• Intense exercise, especially when blood glucose may be low, should be avoided.

Nutrition

• Caloric intake should be timed at 12-hour intervals, at a fixed time every day, just prior to insulin injections.
• The amount of food fed at each meal should also be fixed. In dogs, a diet high in insoluble fiber promotes weight loss, gradual carbohydrate absorption, decreased postprandial blood glucose fluctuations, and increased insulin sensitivity
• Complex carbohydrates and a fixed protein and restricted fat content also contribute to gradual carbohydrate absorption and decreased postprandial blood glucose fluctuations as well as weight loss.