How do you diagnose euglycemic diabetic ketoacidosis (DKA) in a patient with normal or slightly elevated blood glucose levels?

How to Diagnose Euglycemic DKA

Euglycemic DKA is diagnosed when metabolic acidosis (venous pH <7.3, bicarbonate <15 mEq/L) and elevated blood β-hydroxybutyrate are present despite blood glucose <250 mg/dL—the traditional hyperglycemia threshold is no longer required for DKA diagnosis. 1, 2

Core Diagnostic Criteria

The diagnosis requires three components present simultaneously, but hyperglycemia has been de-emphasized in recent guidelines 2:

• Metabolic acidosis: Venous pH <7.3 AND serum bicarbonate <15 mEq/L 1, 3
• Ketosis: Elevated blood β-hydroxybutyrate (β-OHB) 1, 3
• Blood glucose: Can be <250 mg/dL (and even <200 mg/dL) in euglycemic DKA 1, 4, 5

The anion gap should be calculated as [Na⁺] - ([Cl⁻] + [HCO₃⁻]), with a result >10-12 mEq/L supporting the diagnosis 1, 6.

Essential Laboratory Workup

Order these tests immediately upon suspicion 1, 3:

• Blood glucose (even if <250 mg/dL, do not rule out DKA) 1, 2
• Venous blood gas for pH and bicarbonate (arterial puncture is unnecessary) 1, 6
• Blood β-hydroxybutyrate (β-OHB) - this is the preferred ketone measurement 1, 3, 6
• Complete metabolic panel including electrolytes, BUN, creatinine, and calculated osmolality 1, 3
• Anion gap calculation 1, 6
• Complete blood count with differential to identify infection as a precipitating cause 1
• Urinalysis (though less reliable than blood ketones) 1
• Electrocardiogram to evaluate cardiac complications and hyperkalemia 1
• HbA1c to distinguish acute decompensation from chronic poor control 1

Critical Ketone Measurement Considerations

Do NOT rely on urine ketones or nitroprusside-based tests for diagnosis. 3, 6

• The nitroprusside method only measures acetoacetate and acetone, completely missing β-OHB, which is the predominant ketone in DKA 3, 6
• Urine ketones can be falsely negative early in DKA 3
• During treatment, β-OHB is converted to acetoacetate, which paradoxically makes nitroprusside tests appear worse even as the patient improves 6
• Direct blood β-OHB measurement is mandatory for both diagnosis and monitoring 3, 6

High-Risk Clinical Scenarios for Euglycemic DKA

Maintain high suspicion in these situations 1, 4, 5:

• SGLT2 inhibitor use (most common cause in current practice) 1, 3, 4, 5
• Pregnancy 4, 5
• Reduced caloric intake or fasting 1, 4, 5
• Ketogenic diets 1
• Recent insulin administration (may lower glucose but not clear ketones without adequate carbohydrate) 4
• Heavy alcohol consumption 4
• Chronic liver disease 4, 5
• Bariatric surgery or gastroparesis 5
• Insulin pump failure 5

Severity Classification Once Diagnosed

Classify severity based on pH and bicarbonate, NOT glucose 1, 3:

• 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/lethargic 1, 3
• Severe: pH <7.00, bicarbonate <10 mEq/L, stuporous or comatose 1, 3, 6

Differential Diagnosis to Exclude

Consider and rule out these alternative causes of high anion gap metabolic acidosis 1, 5:

• Starvation ketosis: Glucose rarely >250 mg/dL and bicarbonate usually not <18 mEq/L 1
• Alcoholic ketoacidosis: Clinical history of alcohol use, glucose ranges from mildly elevated to hypoglycemic 1
• Lactic acidosis: Elevated lactate levels and different clinical context 1
• Toxic ingestions: Salicylates, methanol, ethylene glycol (identified by history and specific toxicology) 1
• Chronic renal failure: Typically causes hyperchloremic acidosis rather than high anion gap 1

Monitoring During Evaluation and Treatment

Once euglycemic DKA is suspected or confirmed 1, 3, 6:

• Repeat labs every 2-4 hours for electrolytes, glucose, BUN, creatinine, venous pH, β-OHB, and anion gap 1, 3, 6
• Avoid repeated arterial blood gases—venous pH (typically 0.03 units lower than arterial) is sufficient for monitoring after initial diagnosis 1, 6
• Potassium levels are essential before starting insulin, as insulin drives potassium intracellularly and can precipitate life-threatening hypokalemia 1

Resolution Criteria

Euglycemic DKA is definitively resolved when ALL of the following are present 1, 3, 6:

• Glucose <200 mg/dL 1, 6
• Venous pH >7.3 1, 3, 6
• Serum bicarbonate ≥18 mEq/L 1, 3, 6
• Anion gap ≤12 mEq/L 1, 3, 6

Note that ketonemia (β-OHB) clears more slowly than hyperglycemia, so β-OHB may remain elevated even after other parameters normalize 1, 6.

Common Diagnostic Pitfalls to Avoid

• Do not dismiss DKA possibility because glucose is <250 mg/dL—euglycemic DKA is increasingly common, especially with SGLT2 inhibitors 1, 3, 2
• Do not rely on urine ketones for diagnosis—they miss β-OHB and can be falsely negative early in DKA 3, 6
• Do not stop monitoring β-OHB when glucose normalizes—ketoacidosis takes longer to resolve than hyperglycemia 1, 6
• Do not use nitroprusside-based ketone tests—they only measure acetoacetate and acetone, not β-OHB 3, 6