What is diabetic ketoalkalosis (DKA) and is it a recognized medical condition?

Diabetic Ketoalkalosis: A Real but Uncommon Variant of DKA

Diabetic ketoalkalosis is a real clinical entity, representing an alkalemic variant of diabetic ketoacidosis (DKA) that occurs in approximately 23% of DKA cases due to concurrent mixed acid-base disorders. 1

What is Diabetic Ketoalkalosis?

Diabetic ketoalkalosis is characterized by:

• Hyperglycemia (>250 mg/dL)
• Increased anion gap (≥16 mmol/L)
• Positive beta-hydroxybutyrate (ketosis)
• Alkalotic pH (>7.4) rather than the acidotic pH typically seen in classic DKA 1

This condition represents a diagnostic challenge because it doesn't meet the traditional criteria for DKA (pH ≤7.3 or bicarbonate ≤18 mmol/L) established by the American Diabetes Association, potentially leading to delayed diagnosis and treatment. 2, 3

Pathophysiology

The alkalotic pH in diabetic ketoalkalosis results from mixed acid-base disorders that overcome the primary metabolic acidosis of ketone production:

• Primary ketoacidosis: Always present (increased anion gap metabolic acidosis)
• Concurrent disorders that lead to alkalemia:
  • Metabolic alkalosis (present in 47.2% of cases) - often from vomiting or diuretic use
  • Respiratory alkalosis (present in 81.1% of cases) - from hyperventilation, pain, or anxiety
  • Rarely, respiratory acidosis (11.3% of cases) 1

Clinical Significance

Despite the alkalotic pH, diabetic ketoalkalosis requires the same urgent treatment as traditional DKA because:

• 34% of patients with ketoalkalosis have severe ketoacidosis (beta-hydroxybutyrate ≥3 mmol/L) 1
• The underlying metabolic derangements are the same as in classic DKA
• The condition can rapidly progress to acidemia once fluid resuscitation dilutes the compensatory mechanisms 4

Diagnosis

Diagnosis requires a high index of suspicion in patients with:

• Hyperglycemia >250 mg/dL
• Normal or alkalotic pH (>7.4)
• Bicarbonate >20 mEq/L
• Positive serum ketones or elevated beta-hydroxybutyrate
• Increased anion gap 1, 4

Management

Management follows the same principles as traditional DKA:

1. Fluid resuscitation: Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour initially 3
2. Insulin therapy: Continuous IV infusion at 0.1 U/kg/hour without bolus 3
3. Electrolyte replacement: Particularly potassium when levels fall below 5.5 mEq/L 3
4. Frequent monitoring: Vital signs, mental status, blood glucose, electrolytes, pH, and anion gap 3
5. Identification and treatment of precipitating factors: Most commonly infections, new-onset diabetes, or insulin non-adherence 5

Clinical Pitfalls

• Delayed diagnosis: The alkalotic pH may lead clinicians to overlook the underlying ketoacidosis
• Undertreatment: Without recognition of the condition, patients may not receive appropriate DKA management
• Rapid deterioration: As fluid resuscitation progresses, the compensatory alkalosis may resolve, unmasking severe acidosis 4

Prevention

Prevention strategies mirror those for traditional DKA:

• Patient education about insulin adherence
• Sick-day management protocols
• Regular follow-up care
• Early intervention during intercurrent illness 3

The recognition of diabetic ketoalkalosis highlights the importance of comprehensive acid-base assessment in diabetic patients with hyperglycemia, even when pH appears normal or alkalotic. Clinicians should maintain a high index of suspicion and not rely solely on pH or bicarbonate levels to rule out ketoacidosis in hyperglycemic patients.