What is diabetic ketoacidosis (DKA)?

Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes characterized by insulin deficiency resulting in hyperglycemia, ketosis, and metabolic acidosis, requiring immediate medical attention to prevent significant morbidity and mortality. 1

Definition and Pathophysiology

• DKA is caused by absolute or relative insulin deficiency combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) leading to hyperglycemia, ketosis, and metabolic acidosis 2, 1
• The insulin deficiency and hormonal imbalance lead to increased hepatic and renal glucose production, impaired peripheral glucose utilization, and release of free fatty acids into circulation 2
• DKA is traditionally diagnosed by the triad of:
  • Hyperglycemia (blood glucose >250 mg/dL)
  • Metabolic acidosis (pH <7.3, serum bicarbonate <18 mEq/L)
  • Elevated ketone bodies in blood or urine 2, 3
• Euglycemic DKA (glucose <200 mg/dL) can occur with SGLT2 inhibitor use, pregnancy, reduced food intake, alcohol use, or liver failure 2, 1

Severity Classification

• DKA is categorized by acidosis severity 2:
  • Mild: venous pH 7.25-7.30, bicarbonate 15-18 mEq/L
  • Moderate: pH 7.00-7.24, bicarbonate 10-<15 mEq/L
  • Severe: pH <7.00, bicarbonate <10 mEq/L 2

Clinical Presentation

• Common symptoms develop over 24 hours and include:
  • Polyuria, polydipsia, polyphagia
  • Weight loss
  • Nausea, vomiting, abdominal pain (specific to DKA)
  • Dehydration, weakness
  • Kussmaul respirations (deep, rapid breathing)
  • Progressive mental status changes from alertness to lethargy and coma 2, 3
• Physical findings may include:
  • Poor skin turgor
  • Tachycardia, hypotension
  • Altered mental status (more severe in higher severity DKA)
  • Up to 25% of patients have emesis that may be coffee-ground in appearance 2
• Patients can be normothermic or hypothermic despite infection being a common precipitating factor 2

Risk Factors

• Type 1 diabetes/absolute insulin deficiency
• Younger age
• Prior history of hyperglycemic crises
• Presence of other diabetes complications or chronic health conditions
• Behavioral health conditions (depression, bipolar disorder, eating disorders)
• Alcohol and/or substance use
• High A1C level
• Social determinants of health 2
• In children and adolescents: single-parent homes, chronic physical/mental health problems in family members, lack of adequate health insurance 2

Diagnosis

• Laboratory assessment should include:
  • Arterial blood gases to assess pH and bicarbonate levels
  • Serum electrolytes with calculated anion gap
  • Serum ketones (preferred) or urine ketones
  • Blood glucose 1, 3
• Additional tests to consider:
  • Electrolytes, phosphate, BUN, creatinine
  • Complete blood count with differential
  • A1C, ECG
  • Amylase, lipase, hepatic transaminases
  • Blood and urine cultures if infection suspected 3

Treatment

• Fluid therapy:

  • Initial fluid therapy with isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour during first hour to expand intravascular volume and restore renal perfusion 2
  • Continued fluid resuscitation based on hemodynamic status 2, 1

• Insulin therapy:

  • Required to correct hyperglycemia and suppress ketogenesis
  • Typically administered as continuous intravenous infusion 1, 4

• Electrolyte replacement:

  • Particular attention to potassium levels, as insulin therapy can cause hypokalemia 2, 4
  • Phosphate replacement may be necessary 2

• Identify and treat precipitating causes:

  • Infection
  • Medication non-adherence
  • New-onset diabetes
  • Other acute illnesses 1, 4

• Close monitoring:

  • Frequent assessment of vital signs, mental status
  • Regular laboratory monitoring of glucose, electrolytes, pH, and anion gap
  • Adjust therapy based on clinical and laboratory parameters 3

Complications and Prognosis

• Overall mortality for children with DKA is 1-3%, though recent reports from tertiary care centers suggest lower rates 2
• Higher risk for morbidity and mortality with severe DKA 2
• Potential complications include cerebral edema, acute respiratory distress syndrome, thromboembolism, and acute kidney injury 5
• Recurrent DKA is associated with higher diabetes morbidity and mortality compared to patients without DKA episodes 2

Prevention

• Public awareness of signs and symptoms of untreated diabetes
• Education about ketone monitoring
• Recognition that insulin omission due to psychological problems or financial constraints is the most common cause of DKA in established diabetes
• 24-hour healthcare team availability
• Encouragement to contact healthcare providers when blood glucose levels are high or during illness 2
• Patients should not stop basal insulin even when not eating 2
• Detailed instructions on insulin dose adjustments during illness or fasting 2

Special Considerations

• Pregnant individuals may present with euglycemic DKA and have up to 2% incidence of DKA with pregestational diabetes 2
• Recurrent DKA is often associated with insulin omission, psychiatric illness (especially depression), and eating disorders 2
• SGLT2 inhibitors modestly increase risk of DKA and euglycemic DKA 3