Diabetic ketoacidosis (DKA) is a complex metabolic state of hyperglycemia, ketosis, and acidosis. [1, 2] Diabetic ketoacidosis results from untreated absolute or relative deficiency of insulin in type 1 or type 2 diabetes mellitus, respectively.
Hyperglycemia results from impaired glucose uptake because of insulin deficiency and excess glucagon with resultant gluconeogenesis and glycogenolysis. Glucagon excess also increases lipolysis with the formation of ketoacids. Ketone bodies provide alternative usable energy sources in the absence of intracellular glucose. The ketoacids (acetoacetate, beta-hydroxybutyrate, acetone) are products of proteolysis and lipolysis.
Hyperglycemia causes an osmotic diuresis that leads to excessive loss of free water and electrolytes. Resultant hypovolemia leads to tissue hypoperfusion and lactic acidosis.
Ketosis and lactic acidosis produce a metabolic acidosis; however, supplemental bicarbonate is not recommended. Acidosis usually resolves with isotonic fluid volume replenishment and insulin therapy.  A pediatric trial of bicarbonate in severe metabolic acidosis during DKA (pH < 7.15) showed no benefit when compared with placebo.  Indeed, multiple studies suggest that bicarbonate therapy may cause paradoxical intracellular acidosis, worsening tissue perfusion and hypokalemia, and cerebral edema. 
As acidosis corrects, acetoacetate and acetone levels increase in proportion to beta-hydroxybutyrate. As it worsens, the reverse occurs. Routine laboratory testing for ketones measures only the presence of acetoacetate and acetone, not beta-hydroxybutyrate. Therefore, ketosis may appear to be absent in early diabetic ketoacidosis and to worsen as severe diabetic ketoacidosis resolves.
Electrolyte imbalances are the consequences of hyperglycemia, hyperosmolality, and acidosis.
Despite what may be severe total body potassium depletion, apparent serum hyperkalemia is often observed in patients with diabetic ketoacidosis prior to volume resuscitation. Serum hyperkalemia occurs as potassium ions shift from the intracellular to extracellular space because of acidosis from insulin deficiency and decreased renal tubular secretion. Similar decreases in serum phosphate and magnesium concentrations are the result of ion shifts.
Hyponatremia results from a dilutional effect as free water shifts extracellularly because of high serum osmolarity. True serum sodium values can be calculated by adjusting measured sodium levels upward 1.6 mEq/L for every 100 mg/dL increase in serum glucose concentration.
As serum osmolarity increases from hyperglycemia, intracellular osmolality in the brain also increases. Overly rapid correction of serum hyperglycemia and osmolarity may create a large gradient between intracerebral and serum osmolarity. Free water then shifts into the brain and may cause cerebral edema with herniation. Therefore, fluid resuscitation and correction of hyperglycemia should be gradual and closely monitored.
Incidence of type 1 diabetes mellitus is 2 per 1000. The exact incidence of diabetic ketoacidosis is unknown but is estimated to be 4-8 per 1000. Diabetic ketoacidosis occurring at the time of diagnosis of diabetes mellitus is more common in younger children.  In the United States, the rate of diabetic ketoacidosis is about 25% at the time of diagnosis.
Exact incidence is unknown.
Because of an association with human leukocyte antigen (HLA) groups DR3 and DR4 (which occur more commonly in white populations), type 1 diabetes mellitus and diabetic ketoacidosis are more common in white children. The exact racial frequency is unknown.
With current medical therapy, diabetic ketoacidosis has a 2-5% mortality rate. Mortality results from the precipitating underlying cause, which is primarily cerebral edema. Cerebral edema occurs in 0.3-1% of all episodes of diabetic ketoacidosis.
The prognosis is excellent if aggressive fluid and insulin therapy commence in the first few hours of diagnosis.
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