What is Euglycemic Diabetic Ketoacidosis (euDKA)?

Euglycemic Diabetic Ketoacidosis (euDKA)

Euglycemic diabetic ketoacidosis (euDKA) is a life-threatening metabolic emergency characterized by ketoacidosis with normal or near-normal blood glucose levels (<200 mg/dL), requiring immediate recognition and treatment despite the absence of marked hyperglycemia. 1

Definition and Diagnostic Criteria

Euglycemic DKA is defined as:

• Plasma glucose <200 mg/dL (11.1 mmol/L)
• Metabolic acidosis (arterial pH <7.3, serum bicarbonate <15 mEq/L)
• Presence of ketones in blood or urine
• History of diabetes or insulin deficiency 1, 2

Unlike classic DKA which presents with significant hyperglycemia (>250 mg/dL), euDKA can be easily overlooked due to the absence of marked hyperglycemia, leading to delayed diagnosis and treatment.

Pathophysiology

The underlying mechanism of euDKA involves:

• Insulin deficiency (absolute or relative)
• Elevated counterregulatory hormones (glucagon, catecholamines, cortisol)
• Lipolysis and unrestrained hepatic fatty acid oxidation leading to ketone body production
• Relative carbohydrate deficit that maintains near-normal glucose levels while promoting ketosis 1, 3

Risk Factors and Precipitating Factors

Common precipitating factors include:

1. Medication-related:

   • SGLT2 inhibitor use (most common pharmacologic cause) 1, 4, 5, 6
   • Abrupt insulin discontinuation or dose reduction 4

2. Physiological states:

   • Pregnancy (up to 2% of pregnancies with pregestational diabetes) 1
   • Reduced caloric intake or starvation 1, 6

3. Dietary factors:

   • Very low-carbohydrate or ketogenic diets 1, 7
   • Prolonged fasting 1

4. Other conditions:

   • Alcohol consumption 1, 3
   • Liver disease 3
   • Acute illness, particularly infections 5

Clinical Presentation

Patients with euDKA may present with:

• Nausea and vomiting
• Abdominal pain
• Dehydration
• Weakness
• Tachycardia
• Kussmaul respirations (deep, rapid breathing)
• Altered mental status (ranging from mild confusion to coma)
• Normal or only slightly elevated blood glucose (<200 mg/dL) 1, 2

The subtle presentation without marked hyperglycemia can lead to delayed recognition, increasing the risk of morbidity and mortality.

Management

Despite normal glucose levels, management of euDKA follows similar principles to classic DKA:

1. Immediate interventions:

   • Intravenous fluids (including dextrose-containing fluids when glucose is <200 mg/dL)
   • Intravenous insulin therapy
   • Electrolyte monitoring and replacement (particularly potassium)
   • Treatment of underlying precipitating factors 2, 6

2. Monitoring:

   • Hourly vital signs and neurological status
   • Blood glucose every 1-2 hours
   • Electrolytes, BUN, creatinine, and venous pH every 2-4 hours
   • Fluid input/output 2

3. Resolution criteria:

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

Prevention and Patient Education

For patients at risk of euDKA:

• SGLT2 inhibitor users:

  • Temporarily discontinue SGLT2 inhibitors during acute illness, surgery, or reduced oral intake
  • Monitor for symptoms of ketoacidosis even with normal glucose levels
  • Check ketones when symptomatic, regardless of glucose level 1

• All diabetes patients:

  • Never stop basal insulin, even when not eating
  • Follow sick-day management protocols
  • Seek immediate medical attention for persistent vomiting, inability to maintain hydration, or altered mental status 1

Clinical Pitfalls

1. Delayed diagnosis due to normal glucose levels leading clinicians to overlook ketoacidosis
2. Inadequate monitoring of patients on SGLT2 inhibitors during periods of stress or illness
3. Failure to recognize euDKA in pregnant patients with diabetes
4. Inappropriate management by focusing solely on glucose levels rather than addressing ketoacidosis

Special Considerations

• Pregnancy: Pregnant patients are at higher risk for euDKA and require immediate attention due to significant risk of feto-maternal harm 1
• SGLT2 inhibitor users: Consider euDKA in any patient on these medications presenting with nausea, vomiting, or malaise, regardless of glucose level 4, 5, 6
• Ketogenic diet followers: Those following very low-carbohydrate diets may develop euDKA, particularly if they have undiagnosed diabetes 7

Early recognition and prompt treatment of euDKA are essential to prevent complications and reduce mortality, especially since the absence of marked hyperglycemia can mask this serious condition.