What is diabetic ketoacidosis (DKA)?

Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis is a life-threatening complication of diabetes characterized by the triad of hyperglycemia, ketosis, and metabolic acidosis resulting from absolute or relative insulin deficiency combined with elevated counterregulatory hormones. 1, 2

Pathophysiology

• DKA results from a reduction in effective insulin action coupled with increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) 1
• The insulin deficiency and hormonal imbalance lead to:
  • Increased hepatic and renal glucose production 1
  • Impaired glucose utilization in peripheral tissues 1
  • Release of free fatty acids from adipose tissue (lipolysis) 1
  • Unrestrained hepatic fatty acid oxidation producing ketone bodies (β-hydroxybutyrate and acetoacetate) 1
• The hyperglycemia causes osmotic diuresis, leading to significant fluid losses (typically 6-9 liters in adults) and electrolyte depletion 3, 4

Clinical Presentation

• Classical symptoms include polyuria, polydipsia, and polyphagia 4
• Other common symptoms include nausea, vomiting, abdominal pain, weight loss, severe fatigue, and dyspnea 5
• Physical examination may reveal signs of dehydration, Kussmaul respirations (deep, rapid breathing), and a fruity odor of the breath due to acetone 2
• Mental status can range from alert to lethargy and coma in severe cases 1

Diagnostic Criteria

DKA is generally categorized by the severity of acidosis: 1

• Mild DKA: venous pH ≥7.3 and bicarbonate ≥15 mmol/l
• Moderate DKA: pH ≥7.2 with bicarbonate ≥10 mmol/l
• Severe DKA: pH <7.1 and bicarbonate <5 mmol/l

Laboratory findings include: 2, 5

• Hyperglycemia (blood glucose >250 mg/dL), though euglycemic DKA can occur 6
• Metabolic acidosis (pH <7.3, serum bicarbonate <18 mEq/L)
• Elevated anion gap (>10 mEq/L)
• Presence of ketones in blood (preferred) or urine 2
• Electrolyte abnormalities (typically hyponatremia, hypokalemia) 3

Management

1. Fluid Replacement: 1, 2

   • Begin with isotonic saline at 15-20 ml/kg/hour in the first hour
   • Continue fluid resuscitation based on hemodynamic status and electrolyte levels

2. Insulin Therapy: 1, 2

   • For moderate to severe DKA: continuous intravenous regular insulin (0.1 units/kg/hour)
   • For mild DKA: subcutaneous or intramuscular insulin may be effective
   • Target glucose decline of 50-75 mg/dl per hour

3. Electrolyte Replacement: 1, 3

   • Potassium replacement when levels fall below normal or when acidosis begins to resolve
   • Consider phosphate replacement in patients with cardiac dysfunction, anemia, or respiratory depression

4. Monitoring: 1

   • Check blood glucose every 1-2 hours
   • Monitor electrolytes, blood urea nitrogen, creatinine, and venous pH every 2-4 hours
   • Follow ketone levels to monitor resolution of ketoacidosis

5. Bicarbonate Therapy: 1, 2

   • Generally not recommended, even with severe acidosis
   • May be beneficial only in patients with pH <6.9

Special Considerations

• Euglycemic DKA: Can occur with SGLT2 inhibitor use, pregnancy, reduced food intake, or alcohol use 2, 6
• Cerebral Edema: More common in children; requires careful monitoring and gradual correction of glucose and electrolytes 1
• Recurrent DKA: Often due to insulin omission; associated with higher morbidity and mortality; may indicate underlying psychological issues 1

Prevention

Prevention strategies include: 1, 7

• Patient education about signs and symptoms of early DKA
• Regular monitoring of blood glucose and ketones during illness
• 24-hour availability of healthcare team for guidance
• Addressing psychological and financial barriers to insulin adherence
• Ensuring uninterrupted access to insulin and diabetes supplies

Prognosis

• Mortality rate in DKA is approximately 1-5% in experienced centers 1, 8
• Risk factors for poor outcomes include advanced age, presence of coma, hypotension, and severe acidosis 1, 8
• With prompt recognition and appropriate treatment, most patients recover completely 7