What is euglycemic diabetic ketoacidosis (DKA)?

Euglycemic Diabetic Ketoacidosis (DKA)

Euglycemic DKA is a serious, life-threatening condition characterized by metabolic acidosis and ketosis with normal or near-normal blood glucose levels (less than 200 mg/dL), requiring the same urgent treatment as traditional DKA despite the absence of significant hyperglycemia. 1

Definition and Diagnostic Criteria

Euglycemic DKA is defined by:

• Blood glucose levels <200 mg/dL (11.1 mmol/L)
• Arterial pH <7.3
• Serum bicarbonate <15 mEq/L
• Presence of ketonemia or ketonuria 1, 2

This variant represents approximately 10% of all DKA cases and requires a high index of suspicion as the normal glucose levels can mask the underlying ketoacidosis. 1

Pathophysiology

Euglycemic DKA occurs due to:

• Insulin deficiency (absolute or relative)
• Elevated counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone)
• Carbohydrate deficit state while maintaining near-normal glucose levels 3

The key difference from traditional DKA is that various factors prevent significant hyperglycemia while still allowing ketogenesis to occur.

Risk Factors and Precipitating Conditions

Euglycemic DKA is associated with:

1. SGLT2 inhibitor use - These medications increase urinary glucose excretion, maintaining lower blood glucose levels while not preventing ketosis 1, 4

   • Risk factors in patients on SGLT2 inhibitors include:
     • Very low-carbohydrate diets
     • Prolonged fasting
     • Dehydration
     • Excessive alcohol intake
     • Autoimmunity 1

2. Pregnancy - Pregnant women with diabetes are at higher risk of euglycemic DKA due to:

   • Altered metabolism
   • Increased insulin resistance
   • Risk of hyperemesis causing decreased oral intake 1, 2

3. Other precipitating factors:

   • Recent insulin use with insufficient carbohydrate intake
   • Decreased caloric intake or starvation
   • Heavy alcohol consumption
   • Chronic liver disease
   • Glycogen storage disorders
   • Acute illness (infections, pancreatitis)
   • Surgery 3, 5, 6

Clinical Presentation

Patients with euglycemic DKA present with:

• Classic DKA symptoms: polyuria, polydipsia, nausea, vomiting, abdominal pain
• Signs of dehydration
• Kussmaul respirations (deep, rapid breathing)
• Mental status changes ranging from alertness to lethargy
• Metabolic acidosis
• Ketonemia/ketonuria
• Blood glucose <200 mg/dL 2, 3

Diagnostic Challenges

Euglycemic DKA is frequently missed or diagnosed late because:

• Normal blood glucose levels mask the underlying ketoacidosis
• Providers may not check for ketones when glucose levels are normal
• Symptoms may be attributed to other causes 5, 7

Management

Despite the euglycemia, management follows the same principles as traditional DKA:

1. Intravenous fluids - Correct dehydration with isotonic saline
2. Insulin therapy - IV insulin infusion is required despite normal glucose levels
   • Continue insulin until ketoacidosis resolves (not just until glucose normalizes)
   • Monitor glucose closely to prevent hypoglycemia
3. Electrolyte replacement - Particularly potassium
4. Identify and treat precipitating factors
5. Discontinue SGLT2 inhibitors if applicable 2, 7

DKA is considered resolved when:

• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap normalized 2

Special Considerations

SGLT2 Inhibitor-Associated Euglycemic DKA

If a patient on SGLT2 inhibitors (like empagliflozin) presents with signs of metabolic acidosis:

• Assess for ketoacidosis regardless of blood glucose levels
• Discontinue the SGLT2 inhibitor
• Initiate prompt treatment with insulin, fluids, and carbohydrates 4

The FDA warns that ketoacidosis associated with SGLT2 inhibitors may present with blood glucose levels below 250 mg/dL. 4

Prevention in High-Risk Patients

For patients on SGLT2 inhibitors:

• Consider temporarily discontinuing the medication during periods of acute illness, surgery, or prolonged fasting
• Monitor for ketones during these high-risk periods
• Maintain adequate hydration and carbohydrate intake 4

For pregnant patients with diabetes:

• Maintain vigilant monitoring
• Seek immediate medical attention for any signs of illness 1

Key Clinical Pitfalls

1. Delayed diagnosis due to normal glucose levels
2. Inadequate treatment duration - stopping insulin too early when glucose normalizes
3. Failure to identify precipitating factors
4. Not considering euglycemic DKA in patients on SGLT2 inhibitors with symptoms of acidosis

Conclusion

Euglycemic DKA represents a diagnostic challenge requiring high clinical suspicion. Despite normal glucose levels, it remains a medical emergency requiring the same aggressive treatment as traditional DKA to prevent significant morbidity and mortality.