Diabetes Mellitus

The most important disease of the endocrine pancreas is diabetes mellitus (DM), which has been documented in many domestic species but is particularly prevalent in dogs and cats. DM causes an array of laboratory changes, including fasting hyperglycemia and glucosuria.

Glucose regulation

In the normal animal, insulin release following a meal causes the excess carbohydrate not required for immediate cellular metabolism to be stored as glycogen, mainly in the liver, but also in muscles. This action prevents marked increases in blood glucose following a meal. Additional excess carbohydrate and fat are stored in adipose tissues. Insulin promotes cellular uptake of amino acids and their conversion into protein, and inhibits the breakdown of existing cellular proteins.

When insulin is not being released (i.e. between meals), its effects are reversed through the action of glucagon. Glucagon is released from the alpha cells of the islets of Langerhans in response to low blood glucose, ensuring that blood glucose levels remain stabilized and hypoglycemia does not develop. In the short term, epinephrine release also protects against hypoglycemia. Over longer periods, growth hormone and cortisol decrease glucose utilization by most cells, and cells convert to fat utilization to prevent hypoglycemia. Progesterone promotes growth hormone release from mammary gland epithelium, therefore, sexually intact female animals can develop progesterone-related hyperglycemia at certain times of the estrus cycle and during pregnancy. Preclinical DM can become clinical, or diabetic animals receiving treatment can become difficult to regulate at these times.

DM is caused by lack of insulin (type 1) or insulin resistance by target tissues (type 2). Type 1 DM results from hypoplasia or destruction of pancreatic β cells and is more common in dogs. Type 2 DM results from decreased insulin production and a poor tissue response to insulin, and is more common in cats. The pathogenesis of type 2 DM in cats is not completely understood, but amyloid deposition in pancreatic islets may play a role. Animals with type 1 DM generally respond well to insulin therapy, and animals with type 2 disease may respond well, partially, or not at all to insulin therapy. The insulin effectiveness in diabetic cats can change over time or change back and forth.

The classic signs of DM are polyuria, polydipsia, polyphagia, and weight loss. Urinary tract infection is often present and there may be a lack of local leukocyte response to the infection, i.e. no pyuria detected on urine sediment examination. Affected animals are not necessarily ill, although protein catabolism can lead to weakness and lethargy. In the absence of insulin, excessive formation of ketone bodies from fats leads to ketosis and acidosis. Ketoacidotic diabetic animals are very ill with marked lethargy, anorexia, and vomiting. Volume contraction may lead to azotemia and concurrent diseases are possible, particularly given the older age of diabetic animals. Pancreatitis is one of the most common diseases to accompany or predispose to DM.

CBC findings

The CBC is usually within reference limits in diabetic animals unless the animal is dehydrated, as reflected in elevated hematocrit and total protein, or concurrent infection is present, as reflected in an inflammatory leukogram. Hypertriglyceridemia due to disturbed lipid metabolism, renders the plasma and serum lipemic which interferes with refractometric protein determination. Hypercholesterolemia, also from disturbed lipid metabolism, is not associated with visible lipemia, but artificially increases the protein reading by refractometry.

Biochemical panel and urinalysis findings

Serum biochemical findings depend on the duration and severity of illness. Uncomplicated diabetics have fasting hyperglycemia, hypercholesterolemia, and elevations in hepatic enzyme activities (due to hepatic lipidosis). Osmotic diuresis results in renal sodium and chloride losses causing hyponatremia and hypochloremia. In addition, hyperglycemia causes intracellular fluid to be drawn into the extracellular/intravascular fluid (plasma), which exacerbates the hyponatremia and hypochloremia. Ketonuria, if present, also promotes renal excretion of sodium. Serum potassium is variable although total body potassium is often decreased. Close monitoring of serum potassium is recommended when insulin therapy is instituted since insulin promotes potassium movement into cells from the ECF; insulin has a similar effect on serum phosphorus.

Hyperglycemia leads to glucosuria when the renal threshold for glucose reabsorption is exceeded. Glucosuria occurs when serum glucose is >10 mmol/L (>180 mg/dL) in the dog and horse, >15 mmol/L (>280 mg/dL) in the cat, and >5.6 mmol/L (>100 mg/dL) in cattle. Severe hyperosmolality of >350-400 mOsm/kg can seriously complicate treatment of the diabetic patient. Ketonuria may occur as a result of fat degradation given the inability to utilize carbohydrates.

Complications of diabetes mellitus

Diabetic ketoacidosis is a potential serious complication of DM that results from the accumulation of ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone) formed from oxidation of free fatty acids. Excessive production of ketone bodies may occur in uncontrolled DM, resulting in their accumulation in the circulation (called ketonemia) and the development of ketosis. Ketone bodies are organic acids and their accumulation causes a high anion gap metabolic acidosis.

Diabetic hyperosmolar hyperglycemic state (HHS) is an uncommon complication of DM in dogs and cats. This syndrome is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketosis. As hyperosmolality becomes more severe, the patient may become comatose due to water being drawn out of neurons. Concurrent disorders are common with this syndrome and have a negative impact on the prognosis. These disorders include renal disease, congestive heart failure, infection, pancreatitis, and pulmonary disease. It is believed that concurrent diseases may promote insulin resistance and secretion of other hormones (e.g. catecholamines, cortisol) that exacerbate the hyperglycemia.