Diabetic Ketoacidosis (DKA) is a serious and life-threatening complication of diabetes mellitus that can occur in dogs and cats. DKA is characterized by hyperglycemia, ketonemia, +/- ketonuria, and metabolic acidosis. Ketone bodies are formed by lipolysis (breakdown) of fat and beta-oxidation when the metabolic demands of the cells are not met by the limited intracellular glucose concentrations. This provides alternative energy sources for cells, which are most important for the brain. The three ketones that are formed include beta-hydroxybutyrate, acetoacetate and acetone. Beta-hydroxybutyrate (BHB) and acetoacetate are anions of moderately strong acids contributing most to the academia (low blood pH). Acetone is the ketone body that can be detected on breath.
In a normal animal, glucose enters the cell (with help of insulin) – undergoes glycolysis to pyruvate within cytosol – pyruvate moves into mitochondria (energy generating organelle in the cell) to enter the TCA cycle and ATP is formed. ATP is the main energy source of the body.
When glucose cannot enter the cell, free fatty acids are broken down (lipolysis) and move into the cell to undergo beta-oxidation (creation of pyruvate). The pyruvate then moves into the mitochondria to enter the TCA cycle (by conversion to Acetyl-CoA first). However, when the TCA cycle is overwhelmed, the Acetyl-CoA is used in ketogenesis to form ketone bodies.
Now to the clinically important stuff…
There are some differences in the historical and exam findings, risk factors and blood results between dogs and cats. Below are some tips on cats followed by dogs.
Historical findings: Polyuria, polydipsia, weight loss, anorexia, vomiting and lethargy.
Physical exam findings: Thin body condition, dehydration, icterus and hepatomegaly.
Risk factors: Mean age 9 years (range 2 years to 16 years). No breed or sex predilections. Concurrent disease in 90% of cats with DKA (CKD, acute pancreatitis, hepatic lipidosis, UTI/other infection and neoplasia most common). Most DKA cats are newly diagnosed diabetics.
CBC findings: Anemia, neutrophilia with left shift and Heinz bodies (thought to be correlated to Beta-hydroxybutyrate concentrations).
Biochemical findings: Hyperglycemia, ketonemia, acidemia, elevated ALT, hypercholesterolemia, azotemia, hyponatremia (pseudo), normokalemia or hyperkalemia, normophosphatemia or hyperphosphatemia and hypomagnesemia. Potassium and phosphorus levels will drop with fluid therapy. Azotemia more common in cats than dogs.
Historical findings: Polyuria, polydipsia, weight loss, anorexia, vomiting and lethargy.
Physical exam findings: Overweight or underweight, dehydration, cranial abdominal organomegaly, heart murmur, mental dullness, abdominal pain, dyspnea, coughing, abnormal lung sounds and cataracts.
Risk factors: Median age 8 years (range 8 months to 16 years). No breed or sex predilections. Concurrent disease in approximately 70% of dogs with DKA (acute pancreatitis, UTI and hyperadrenocorticism most common). 20% have UTI.
CBC findings: 50% of dogs have non-regenerative anemia. Neutrophilia with left shift and thrombocytosis also common.
Biochemical findings: Hyperglycemia, ketonemia, acidemia, elevated ALP (almost all dogs with DKA). Elevated ALT, AST and hypercholesterolemia in approximately half of dogs. Hyponatremia (pseudo), normokalemia or hyperkalemia, normophosphatemia or hyperphosphatemia and hypomagnesemia. Potassium and phosphorus levels will drop with fluid therapy. Hypchloremia and decreased ionized calcium concentrations in approximately 50% of dogs with DKA. Hyperlactatemia in approximately 1/3 of dogs.
BHB is the first ketone body formed but isn’t detected in the ketone sticks. Ketones develop in the blood before the urine so you can use plasma to diagnose for ketones earlier. This can be done on the urine dipsticks that look for ketones so there is no need for additional equipment.
Goal of treatment of DKA in dogs and cats is rehydration, drop glucose, normalizing pH, eliminate ketones, manage electrolyte imbalances and address concurrent diseases or underlying disease.
Treatment includes aggressive fluid therapy (most important), potassium and phosphorus supplementation, insulin therapy and possible bicarbonate administration (rarely needed).
Insulin therapy is also a mainstay of DKA therapy. Two main protocols include regular insulin constant rate infusion (CRI) or regular insulin intermittent intramuscular (IM). The blood glucose (BG) is measured every 2 hours with CRI. BG is measured every hour with IM.
Bicarbonate therapy is described but is only reserved for severely acidemic patients (generally, pH less than 7 after 1 hour of fluid therapy per American Diabetes Association). This is not commonly performed. Risks in humans include cerebral edema, increased ketogenesis, worsening hypokalemia, and paradoxical cerebral acidosis. One protocol is: administer 1/2 to 1/3 of a (0.3 x body weight (kg) x negative base excess) dose over twenty-minute interval every hour.