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Diabetic Ketoacidosis (DKA)

By Erika F. Brutsaert, MD, Assistant Professor;Attending Physician, Albert Einstein College of Medicine;Montefiore Medical Center

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Diabetic ketoacidosis is an acute metabolic complication of diabetes characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia causes an osmotic diuresis with significant fluid and electrolyte loss. DKA occurs mostly in type 1 diabetes mellitus (DM). It causes nausea, vomiting, and abdominal pain and can progress to cerebral edema, coma, and death. DKA is diagnosed by detection of hyperketonemia and anion gap metabolic acidosis in the presence of hyperglycemia. Treatment involves volume expansion, insulin replacement, and prevention of hypokalemia.

(See also Diabetes Mellitus.)

Diabetic ketoacidosis (DKA) is most common among patients with type 1 diabetes mellitus and develops when insulin levels are insufficient to meet the body’s basic metabolic requirements. DKA is the first manifestation of type 1 DM in a minority of patients. Insulin deficiency can be absolute (eg, during lapses in the administration of exogenous insulin) or relative (eg, when usual insulin doses do not meet metabolic needs during physiologic stress).

Common physiologic stresses that can trigger DKA include

Some drugs implicated in causing DKA include

  • Corticosteroids

  • Thiazide diuretics

  • Sympathomimetics

  • Sodium-glucose co-transporter 2 (SGLT-2) inhibitors

DKA is less common in type 2 diabetes mellitus, but it may occur in situations of unusual physiologic stress. Ketosis-prone type 2 diabetes is a variant of type 2 diabetes, which is sometimes seen in obese individuals, often of African (including African-American or Afro-Caribbean) origin. People with ketosis-prone diabetes (also referred to as Flatbush diabetes) can have significant impairment of beta cell function with hyperglycemia, and are therefore more likely to develop DKA in the setting of significant hyperglycemia. SGLT-2 inhibitors have been implicated in causing DKA in both type 1 and type 2 DM.


Insulin deficiency causes the body to metabolize triglycerides and amino acids instead of glucose for energy. Serum levels of glycerol and free fatty acids (FFAs) rise because of unrestrained lipolysis, as does alanine because of muscle catabolism. Glycerol and alanine provide substrate for hepatic gluconeogenesis, which is stimulated by the excess of glucagon that accompanies insulin deficiency.

Glucagon also stimulates mitochondrial conversion of FFAs into ketones. Insulin normally blocks ketogenesis by inhibiting the transport of FFA derivatives into the mitochondrial matrix, but ketogenesis proceeds in the absence of insulin. The major ketoacids produced, acetoacetic acid and beta-hydroxybutyric acid, are strong organic acids that create metabolic acidosis. Acetone derived from the metabolism of acetoacetic acid accumulates in serum and is slowly disposed of by respiration.

Hyperglycemia due to insulin deficiency causes an osmotic diuresis that leads to marked urinary losses of water and electrolytes. Urinary excretion of ketones obligates additional losses of sodium and potassium. Serum sodium may fall due to natriuresis or rise due to excretion of large volumes of free water. Potassium is also lost in large quantities, sometimes > 300 mEq/24 h. Despite a significant total body deficit of potassium, initial serum potassium is typically normal or elevated because of the extracellular migration of potassium in response to acidosis. Potassium levels generally fall further during treatment as insulin therapy drives potassium into cells. If serum potassium is not monitored and replaced as needed, life-threatening hypokalemia may develop.

Symptoms and Signs

Symptoms and signs of diabetic ketoacidosis include symptoms of hyperglycemia with the addition of nausea, vomiting, and—particularly in children—abdominal pain. Lethargy and somnolence are symptoms of more severe decompensation. Patients may be hypotensive and tachycardic due to dehydration and acidosis; they may breathe rapidly and deeply to compensate for acidemia (Kussmaul respirations). They may also have fruity breath due to exhaled acetone. Fever is not a sign of DKA itself and, if present, signifies underlying infection. In the absence of timely treatment, DKA progresses to coma and death.

Acute cerebral edema, a complication in about 1% of DKA patients, occurs primarily in children and less often in adolescents and young adults. Headache and fluctuating level of consciousness herald this complication in some patients, but respiratory arrest is the initial manifestation in others. The cause is not well understood but may be related to too-rapid reductions in serum osmolality or to brain ischemia. It is most likely to occur in children < 5 yr when DKA is the initial manifestation of diabetes mellitus. Children with the highest BUN and lowest Paco2 at presentation appear to be at greatest risk. Delays in correction of hyponatremia and the use of bicarbonate during DKA treatment are additional risk factors.


  • Arterial pH

  • Serum ketones

  • Calculation of anion gap

In patients suspected of having diabetic ketoacidosis, serum electrolytes, BUN and creatinine, glucose, ketones, and osmolarity should be measured. Urine should be tested for ketones. Patients who appear significantly ill and those with positive ketones should have arterial blood gas measurement.

DKA is diagnosed by an arterial pH < 7.30 with an anion gap > 12 (see The Anion Gap) and serum ketones in the presence of hyperglycemia. A presumptive diagnosis can be made when urine glucose and ketones are strongly positive. Urine test strips and some assays for serum ketones may underestimate the degree of ketosis because they detect acetoacetic acid and not beta-hydroxybutyric acid, which is usually the predominant ketoacid.

Symptoms and signs of a triggering illness should be pursued with appropriate studies (eg, cultures, imaging studies). Adults should have an ECG to screen for acute myocardial infarction and to help determine the significance of abnormalities in serum potassium.

Other laboratory abnormalities include hyponatremia, elevated serum creatinine, and elevated plasma osmolality. Hyperglycemia may cause dilutional hyponatremia, so measured serum sodium is corrected by adding 1.6 mEq/L for each 100 mg/dL elevation of serum glucose over 100 mg/dL. To illustrate, for a patient with serum sodium of 124 mEq/L and glucose of 600 mg/dL, add 1.6 ([600 100]/100) = 8 mEq/L to 124 for a corrected serum sodium of 132 mEq/L. As acidosis is corrected, serum potassium drops. An initial potassium level <4.5 mEq/L indicates marked potassium depletion and requires immediate potassium supplementation.

Serum amylase and lipase are often elevated, even in the absence of pancreatitis (which may be present in patients with alcoholic ketoacidosis and in those with coexisting hypertriglyceridemia).


Overall mortality rates for diabetic ketoacidosis are < 1%; however, mortality is higher in the elderly and in patients with other life-threatening illnesses. Shock or coma on admission indicates a worse prognosis. Main causes of death are circulatory collapse, hypokalemia, and infection. Among children with cerebral edema, about 57% recover completely, 21% survive with neurologic sequelae, and 21% die.


  • IV 0.9% saline

  • Correction of any hypokalemia

  • IV insulin (as long as serum potassium is 3.3 mEq/L)

  • Rarely IV sodium bicarbonate (if pH < 7 after 1 h of treatment)

The most urgent goals for treating diabetic ketoacidosis are rapid intravascular volume repletion, correction of hyperglycemia and acidosis, and prevention of hypokalemia (1). Identification of precipitating factors is also important. Treatment should occur in intensive care settings because clinical and laboratory assessments are initially needed every hour or every other hour with appropriate adjustments in treatment.

Volume repletion

Intravascular volume should be restored rapidly to raise blood pressure and ensure glomerular perfusion; once intravascular volume is restored, remaining total body water deficits are corrected more slowly, typically over about 24 h. Initial volume repletion in adults is typically achieved with rapid IV infusion of 1 to 3 L of 0.9% saline solution, followed by saline infusions at 1 L/h or faster as needed to raise blood pressure, correct hyperglycemia, and keep urine flow adequate. Adults with diabetic ketoacidosis typically need a minimum of 3 L of saline over the first 5 h. When blood pressure is stable and urine flow adequate, normal saline is replaced by 0.45% saline. When plasma glucose falls to < 200 mg/dL (11.1 mmol/L), IV fluid should be changed to 5% dextrose in 0.45% saline.

For children, fluid deficits are estimated at 60 to 100 mL/kg body weight. Pediatric maintenance fluids (for ongoing losses) must also be provided. Initial fluid therapy should be 0.9% saline (20 mL/kg) over 1 to 2 h, followed by 0.45% saline once blood pressure is stable and urine output adequate. The remaining fluid deficit should be replaced over 36 h, typically requiring a rate (including maintenance fluids) of about 2 to 4 mL/kg/h, depending on the degree of dehydration.

Correction of hyperglycemia and acidosis

Hyperglycemia is corrected by giving regular insulin 0.1 unit/kg IV bolus initially, followed by continuous IV infusion of 0.1 unit/kg/h in 0.9% saline solution. Insulin should be withheld until serum potassium is 3.3 mEq/L (see Hyperosmolar Hyperglycemic State (HHS) : Treatment). Insulin adsorption onto IV tubing can lead to inconsistent effects, which can be minimized by preflushing the IV tubing with insulin solution. If plasma glucose does not fall by 50 to 75 mg/dL (2.8 to 4.2 mmol/L) in the first hour, insulin doses should be doubled. Children should be given a continuous IV insulin infusion of 0.1 unit/kg/h or higher with or without a bolus.

Ketones should begin to clear within hours if insulin is given in sufficient doses. However, clearance of ketones may appear to lag because of conversion of beta-hydroxybutyrate to acetoacetate (which is the “ketone” measured in most hospital laboratories) as acidosis resolves. Serum pH and bicarbonate levels should also quickly improve, but restoration of a normal serum bicarbonate level may take 24 h. Rapid correction of pH by bicarbonate administration may be considered if pH remains < 7 after about an hour of initial fluid resuscitation, but bicarbonate is associated with development of acute cerebral edema (primarily in children) and should not be used routinely. If used, only modest pH elevation should be attempted (target pH of about 7.1), with doses of 50 to 100 mEq over 30 to 60 min, followed by repeat measurement of arterial pH and serum potassium.

When plasma glucose becomes < 200 mg/dL (< 11.1 mmol/L) in adults, 5% dextrose should be added to IV fluids to reduce the risk of hypoglycemia. Insulin dosage can then be reduced to 0.02 to 0.05 unit/kg/h, but the continuous IV infusion of regular insulin should be maintained until the anion gap has narrowed and blood and urine are consistently negative for ketones. Insulin replacement may then be switched to regular insulin 5 to 10 units sc q 4 to 6 h. When the patient is stable and able to eat, a typical split-mixed or basal-bolus insulin regimen is begun. IV insulin should be continued for 1 to 4 h after the initial dose of sc insulin is given. Children should continue to receive 0.05 unit/kg/h insulin infusion until sc insulin is initiated and pH is > 7.3.

Hypokalemia prevention

Hypokalemia prevention requires replacement of 20 to 30 mEq potassium in each liter of IV fluid to keep serum potassium between 4 and 5 mEq/L. If serum potassium is < 3.3 mEq/L, insulin should be withheld and potassium given at 40 mEq/h until serum potassium is 3.3 mEq/L; if serum potassium is > 5 mEq/L, Potassium supplementation can be withheld.

Initially normal or elevated serum potassium measurements may reflect shifts from intracellular stores in response to acidemia and belie the true potassium deficits that almost all patients with diabetic ketoacidosis have. Insulin replacement rapidly shifts potassium into cells, so levels should be checked hourly or every other hour in the initial stages of treatment.

Other measures

Hypophosphatemia often develops during treatment of DKA, but phosphate repletion is of unclear benefit in most cases. If indicated (eg, if rhabdomyolysis, hemolysis, or neurologic deterioration occurs), potassium phosphate, 1 to 2 mmol/kg of phosphate, can be infused over 6 to 12 h. If potassium phosphate is given, the serum calcium level usually decreases and should be monitored.

Treatment of suspected cerebral edema is hyperventilation, corticosteroids, and mannitol, but these measures are often ineffective after the onset of respiratory arrest.

Treatment reference

Key Points

  • Acute physiologic stressors (eg, infections, myocardial infarction) can trigger acidosis, moderate glucose elevation, dehydration, and severe potassium loss in patients with type 1 diabetes.

  • Acute cerebral edema is a rare (about 1%) but lethal complication, primarily in children and less often in adolescents and young adults.

  • Diagnose by an arterial pH < 7.30, with an anion gap > 12 and serum ketones in the presence of hyperglycemia.

  • Acidosis typically corrects with IV fluid and insulin; consider bicarbonate only if marked acidosis (pH < 7) persists after 1 hr of therapy.

  • Withhold insulin until serum potassium is 3.3 mEq/L