How is euglycemic diabetic ketoacidosis (DKA) diagnosed and treated?

Diagnosis of Euglycemic Diabetic Ketoacidosis

Euglycemic DKA is diagnosed when blood glucose is <250 mg/dL (often <200 mg/dL) in the presence of metabolic acidosis (pH <7.3, bicarbonate <15-18 mEq/L), elevated anion gap (>10-12 mEq/L), and positive ketones—particularly elevated β-hydroxybutyrate. 1, 2, 3

Core Diagnostic Criteria

The diagnosis requires all three components of the "DKA triad" but with euglycemia rather than typical hyperglycemia:

• Blood glucose <250 mg/dL (and often substantially lower, with cases reported as low as 75 mg/dL) 3, 4, 5
• Metabolic acidosis: venous pH <7.3 and serum bicarbonate <15-18 mEq/L 1, 2
• Elevated ketones: positive serum or urine ketones, with β-hydroxybutyrate measurement preferred 1, 2
• Anion gap >10-12 mEq/L: calculated as [Na+] - ([Cl-] + [HCO3-]) 1, 2

Essential Laboratory Evaluation

Obtain these tests immediately when euglycemic DKA is suspected:

• Venous blood gas for pH and bicarbonate (arterial not required after initial assessment) 6, 2
• Complete metabolic panel including electrolytes, BUN, creatinine, and calculated anion gap 2, 7
• Direct β-hydroxybutyrate measurement in blood—this is the preferred test, not nitroprusside-based urine ketones 1, 2
• Serum osmolality and corrected sodium (add 1.6 mEq/L for every 100 mg/dL glucose above 100) 1, 2
• Urinalysis with ketones 1, 7
• Complete blood count and cultures if infection suspected 1, 7

Critical Diagnostic Pitfall

Do not rely on urine ketones or nitroprusside-based tests for diagnosis or monitoring. These methods only detect acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant ketone in DKA. 1, 2 During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves. 1, 2

High-Risk Clinical Scenarios for Euglycemic DKA

Maintain high clinical suspicion in these settings:

• SGLT2 inhibitor use (empagliflozin, canagliflozin, dapagliflozin)—the most common modern cause 4, 5, 8
• Recent insulin administration prior to presentation (57% of cases) 5, 8
• Starvation or poor oral intake with baseline insulin use (29% of cases) 3, 5, 8
• Pregnancy 1, 8
• Chronic liver disease 8
• Alcohol use 1, 8
• Latent autoimmune diabetes in adults (LADA) on SGLT2 inhibitors 4

Differential Diagnosis

Rule out other causes of high anion gap metabolic acidosis with ketosis:

• Starvation ketosis: bicarbonate usually not <18 mEq/L, mild glucose elevation only 1
• Alcoholic ketoacidosis: glucose ranges from mildly elevated to hypoglycemic, clinical history of alcohol use 1
• Other causes of high anion gap acidosis: lactic acidosis, toxic ingestions, uremia 8

Severity Classification

Once diagnosed, classify severity by pH and bicarbonate:

• Mild: pH 7.25-7.30, bicarbonate 15-18 mEq/L 2
• Moderate: pH 7.00-7.24, bicarbonate 10-15 mEq/L 2
• Severe: pH <7.00, bicarbonate <10 mEq/L (requires intensive monitoring) 2

Treatment Approach for Euglycemic DKA

The key difference from hyperglycemic DKA is that dextrose must be started immediately alongside insulin to prevent severe hypoglycemia:

Fluid Resuscitation

• Begin with isotonic saline at 15-20 mL/kg/hour for the first hour 2, 7
• Add dextrose 5% to fluids from the start when glucose is <250 mg/dL 6, 7

Insulin Therapy

• Start continuous IV regular insulin at 0.1 units/kg/hour (bolus optional) 2, 7
• Continue insulin infusion despite euglycemia until ketoacidosis resolves—ketones take longer to clear than glucose 6, 2
• Target glucose 150-200 mg/dL during treatment 6

Electrolyte Management

• Delay insulin if potassium <3.3 mEq/L—aggressively replace potassium first to prevent fatal arrhythmias 2, 7
• Once potassium ≥3.3 mEq/L, add 20-30 mEq/L potassium to IV fluids to maintain levels 4-5 mEq/L 2, 7

Monitoring During Treatment

• Check glucose every 2-4 hours 7
• Monitor electrolytes, venous pH, and β-hydroxybutyrate every 2-4 hours 6, 2
• Hypoglycemia occurs >3 times more frequently in euglycemic DKA (18.2% vs 4.8% in hyperglycemic DKA) 5

Resolution Criteria

DKA is resolved when all of the following are met:

• Glucose <200 mg/dL 6, 2
• Venous pH >7.3 6, 2
• Serum bicarbonate ≥18 mEq/L 6, 2
• Anion gap ≤12 mEq/L 6, 2

Transition to Subcutaneous Insulin

• Administer basal insulin (glargine or detemir) 2-4 hours BEFORE stopping IV insulin to prevent rebound ketoacidosis 6, 7
• Start multiple-dose subcutaneous regimen combining short/rapid-acting and intermediate/long-acting insulin once patient can eat 6, 7

Key Clinical Pearls

Check blood pH and ketones in any ill diabetic patient regardless of glucose level—euglycemia masks the underlying ketoacidosis and creates a diagnostic dilemma. 3, 8 Euglycemic DKA patients typically have milder acidosis on presentation (higher pH, higher bicarbonate, lower anion gap) but require the same aggressive treatment approach. 5 The mean time on insulin infusion is shorter (13.5 vs 19.4 hours) but hypoglycemia risk is substantially higher. 5