What is the pathophysiology and management of euglycemic diabetic ketoacidosis (DKA)?

Euglycemic Diabetic Ketoacidosis: Pathophysiology and Management

Euglycemic diabetic ketoacidosis (DKA) is a serious metabolic emergency characterized by ketoacidosis and relatively normal blood glucose levels (<250 mg/dL), requiring the same urgent treatment approach as traditional DKA despite the absence of significant hyperglycemia. 1

Pathophysiology

Euglycemic DKA develops through several key mechanisms:

1. Relative or absolute carbohydrate deficit - The primary pathophysiological mechanism involves insufficient carbohydrate availability despite continued ketogenesis 2

2. Insulin deficiency with elevated counter-regulatory hormones - Despite lower glucose levels, there remains:

   • Insufficient insulin to suppress lipolysis and ketogenesis
   • Elevated glucagon/insulin ratio promoting ketone body production
   • Continued hepatic ketogenesis despite lower glucose levels 1, 2

3. Common precipitating factors:

   • SGLT2 inhibitor use (increasing incidence)
   • Pregnancy
   • Fasting or severe caloric restriction
   • Ketogenic/low-carbohydrate diets
   • Recent insulin use
   • Alcohol consumption
   • Chronic liver disease
   • Glycogen storage disorders
   • Bariatric surgery
   • Insulin pump failure 1, 3, 2

Diagnostic Approach

Euglycemic DKA is often missed due to the absence of significant hyperglycemia. Diagnosis requires:

1. Laboratory findings:

   • Blood glucose <250 mg/dL
   • Metabolic acidosis (arterial pH <7.3, serum bicarbonate <18 mEq/L)
   • Elevated anion gap
   • Positive serum ketones (β-hydroxybutyrate measurement preferred over nitroprusside method) 4, 1

2. Clinical presentation:

   • Similar to traditional DKA: nausea, vomiting, abdominal pain, dehydration
   • May have tachycardia, Kussmaul respirations
   • Mental status changes possible despite euglycemia 2

Management Approach

Management follows similar principles to traditional DKA with important modifications:

1. Fluid resuscitation:

   • Aggressive IV fluid replacement with isotonic solutions
   • Critical difference: Include dextrose-containing fluids early in treatment 4, 2

2. Insulin therapy:

   • Continuous IV insulin remains the standard of care for moderate to severe cases
   • Important modification: Administer dextrose simultaneously with insulin to prevent hypoglycemia while treating ketoacidosis
   • Consider delaying insulin infusion until glucose levels are >250 mg/dL if starting with very low glucose 4, 3

3. Electrolyte replacement:

   • Careful potassium monitoring and replacement
   • Monitor and replace phosphate as needed, especially with cardiac dysfunction, anemia, or respiratory depression 4

4. Monitoring and transition:

   • Monitor blood glucose every 1-2 hours
   • Check electrolytes, pH, and ketones every 2-4 hours
   • Critical step: Successful transition from IV to subcutaneous insulin requires administration of basal insulin 2-4 hours before stopping IV insulin to prevent recurrence of ketoacidosis 4

5. Resolution criteria:

   • Glucose <200 mg/dL
   • Serum bicarbonate ≥18 mEq/L
   • Venous pH >7.3 4

Special Considerations

1. Bicarbonate therapy:

   • Generally not recommended unless pH <6.9 4
   • Studies have shown no difference in resolution of acidosis or time to discharge with bicarbonate use 4

2. Mild euglycemic DKA:

   • May be treated with subcutaneous insulin in emergency department or step-down units
   • Requires adequate fluid replacement and frequent monitoring 4

3. Identifying and treating underlying causes:

   • Discontinue SGLT2 inhibitors if applicable
   • Treat infections or other precipitating factors
   • Modify dietary factors (especially if ketogenic diet-related) 3, 2

Common Pitfalls to Avoid

1. Delayed diagnosis due to normal or near-normal glucose levels
2. Inadequate dextrose administration during insulin treatment
3. Premature discontinuation of insulin before ketoacidosis resolves
4. Failure to transition properly from IV to subcutaneous insulin
5. Missing underlying precipitating factors that require specific treatment

The key to successful management of euglycemic DKA is maintaining a high index of suspicion in at-risk patients with acidosis, even when glucose levels are normal, and providing prompt treatment with appropriate modifications to standard DKA protocols.