How is euglycemic diabetic ketoacidosis diagnosed and treated in a diabetic patient on an SGL‑2 inhibitor presenting with nausea, vomiting, abdominal pain, tachypnea, and normal or mildly elevated glucose?

Euglycemic Diabetic Ketoacidosis: Diagnosis and Management

In a diabetic patient on an SGLT-2 inhibitor presenting with nausea, vomiting, abdominal pain, tachypnea, and normal or mildly elevated glucose, immediately check venous pH, serum bicarbonate, β-hydroxybutyrate, and anion gap to diagnose euglycemic DKA, then treat with continuous IV insulin infusion plus dextrose-containing fluids until acidosis resolves—not until glucose normalizes. 1, 2, 3

Diagnostic Criteria for Euglycemic DKA

The diagnosis requires three simultaneous findings, with the critical difference being glucose <250 mg/dL instead of the classic >250 mg/dL threshold:

• Metabolic acidosis: Venous pH <7.3 AND serum bicarbonate <18 mEq/L 1, 2
• Elevated ketones: Preferably measured as blood β-hydroxybutyrate (the gold standard), not urine ketones 1, 3
• Normal or mildly elevated glucose: Blood glucose <200-250 mg/dL, despite meeting acidosis criteria 1, 2
• Elevated anion gap: Calculate as [Na⁺] - ([Cl⁻] + [HCO₃⁻]), should be >10-12 mEq/L 1, 3

Approximately 10% of all DKA presentations are euglycemic, and SGLT-2 inhibitors are the most common modern precipitant. 1, 4

Critical Diagnostic Pitfall to Avoid

Never rely on urine ketone dipsticks or nitroprusside-based tests for diagnosis or monitoring. These methods only detect acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant and strongest ketoacid in DKA. 1, 2, 3 During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves. 1, 3

Always order blood β-hydroxybutyrate specifically. 1, 2, 3

Essential Initial Laboratory Workup

When euglycemic DKA is suspected in this clinical scenario, obtain immediately:

• Venous blood gas (pH and bicarbonate—arterial gas is unnecessary after initial diagnosis) 3
• Blood β-hydroxybutyrate (not urine ketones) 1, 2, 3
• Basic metabolic panel with calculated anion gap 1, 2, 3
• Serum osmolality 2, 3
• Complete blood count with differential 2, 3
• Urinalysis (to assess for infection as precipitant) 2, 3
• Blood and urine cultures if infection suspected 3
• Electrocardiogram (to assess for cardiac complications and potassium effects) 1

Severity Classification

Classify severity to guide monitoring intensity:

• Mild: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status 1, 3
• Moderate: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy mental status 1, 3
• Severe: pH <7.00, bicarbonate <10 mEq/L, stupor/coma—requires intensive monitoring 1, 3

Treatment Algorithm for Euglycemic DKA

Step 1: Aggressive Fluid Resuscitation

Begin isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour for the first hour to restore circulatory volume and tissue perfusion. 2, 3 The typical total body water deficit is 6-9 liters, requiring replacement over 24 hours. 3

Monitor closely for fluid overload in patients with renal or cardiac compromise. 5, 3

Step 2: Potassium Management (Critical Before Insulin)

Check serum potassium immediately and manage before starting insulin:

• If K⁺ <3.3 mEq/L: Delay insulin and aggressively replace potassium first to prevent fatal cardiac arrhythmias 3
• If K⁺ 3.3-5.5 mEq/L: Add 20-30 mEq/L potassium to IV fluids (use 2/3 KCl and 1/3 KPO₄) 5, 3
• If K⁺ >5.5 mEq/L: Hold potassium replacement but recheck frequently 3

Total body potassium is depleted by 3-5 mEq/kg despite normal or elevated initial levels, and insulin drives potassium intracellularly, causing rapid decline. 3

Step 3: Continuous IV Insulin Infusion

Start continuous IV regular insulin at 0.1 units/kg/hour (without an initial bolus) once K⁺ ≥3.3 mEq/L. 3 For a 70 kg patient, this equals approximately 7 units/hour.

If glucose does not fall by 50 mg/dL in the first hour, double the insulin infusion rate hourly until achieving a steady decline of 50-75 mg/dL per hour. 5, 3

Step 4: Add Dextrose Early (The Critical Difference in Euglycemic DKA)

This is where euglycemic DKA management diverges from classic DKA:

When blood glucose falls to 200-250 mg/dL (or is already at this level on presentation), immediately add 5-10% dextrose to IV fluids while continuing the insulin infusion. 2, 3 In euglycemic DKA, you may need to add dextrose from the start if glucose is already <250 mg/dL. 1, 6, 7

Never stop insulin when glucose normalizes. Ketoacidosis takes longer to resolve than hyperglycemia, and premature insulin cessation causes recurrence. 3 Both insulin and glucose are required to clear ketones—insulin alone cannot resolve ketosis without adequate carbohydrate substrate. 3

Step 5: Monitor Every 2-4 Hours

Check the following every 2-4 hours during treatment:

• Blood glucose 3
• Electrolytes (especially potassium) 3
• Venous pH and bicarbonate 3
• Blood β-hydroxybutyrate 3
• Anion gap 3

Venous pH adequately monitors acidosis resolution after initial diagnosis—repeated arterial blood gases are unnecessary. 3

Step 6: Resolution Criteria

DKA is resolved when ALL of the following are met:

• Glucose <200 mg/dL 3
• Venous pH >7.3 3
• Serum bicarbonate ≥18 mEq/L 3
• Anion gap ≤12 mEq/L 3

Do not base resolution on glucose levels alone in euglycemic DKA. 1, 8

Step 7: Transition to Subcutaneous Insulin

Administer basal subcutaneous insulin (NPH, detemir, glargine, or degludec) 2-4 hours before stopping the IV insulin infusion to prevent rebound hyperglycemia and recurrent ketoacidosis. 2, 3 Estimate the basal dose by averaging the IV insulin rate over the preceding 12 hours. 3

Ensure the patient is stable before transition: glucose stable for ≥4-6 hours, normal anion gap, resolved acidosis, hemodynamic stability, and a defined nutrition plan. 3

Special Considerations and Common Pitfalls

Bicarbonate Therapy

Do not administer bicarbonate unless pH <6.9. Routine bicarbonate therapy provides no benefit in acidosis resolution time or hospital length of stay. 3

SGLT-2 Inhibitor Management

Discontinue the SGLT-2 inhibitor immediately and do not restart it. 1, 4 SGLT-2 inhibitors cause euglycemic DKA through noninsulin-dependent glucose clearance, hyperglucagonemia, and volume depletion. 4

The absence of significant hyperglycemia delays recognition by both patients and providers, making this a diagnostic emergency. 9, 4

Precipitating Factors to Address

Beyond SGLT-2 inhibitors, other precipitants include:

• Reduced caloric intake or prolonged fasting 1, 7
• Pregnancy 1
• Alcohol consumption 1
• Acute illness or infection 2, 9
• Insulin omission or pump failure 2, 9

Identify and treat the underlying precipitating cause to prevent recurrence. 3

Monitoring for Complications

Watch for cerebral edema, especially with overly aggressive fluid resuscitation. 3 Monitor mental status continuously to rapidly identify changes indicating iatrogenic complications. 5

Hypokalemia occurs in approximately 50% of patients during treatment, and severe hypokalemia (<2.5 mEq/L) is linked to higher in-hospital mortality. 3

Discharge Planning

Before discharge:

• Discontinue SGLT-2 inhibitor permanently 4
• Identify outpatient diabetes care provider 3
• Provide education on DKA recognition, prevention, and sick-day management 3
• Verify all medication prescriptions are filled and reviewed 3
• Arrange follow-up appointment before discharge 3
• Transmit comprehensive discharge summary to primary care clinician 3