What are the diagnostic criteria for diabetic ketoacidosis (DKA), including severity stratification and special considerations for euglycemic DKA in patients using sodium‑glucose cotransporter‑2 (SGLT2) inhibitors?

Diagnostic Criteria for Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three criteria are simultaneously present: blood glucose >250 mg/dL, venous pH <7.3 with serum bicarbonate <18 mEq/L, and elevated ketones (preferably blood β-hydroxybutyrate). 1

Core Diagnostic Triad

All three of the following must be present to confirm DKA:

• Hyperglycemia: Blood glucose >250 mg/dL 1, 2
• Metabolic acidosis: Venous pH <7.3 AND serum bicarbonate <18 mEq/L 1, 2
• Ketosis: Moderate ketonuria or ketonemia, preferably measured as blood β-hydroxybutyrate 1, 2

The anion gap should be calculated using [Na⁺] - ([Cl⁻] + [HCO₃⁻]) and will typically be >10-12 mEq/L in DKA. 1

Severity Stratification

DKA severity is classified based on the degree of acidosis and mental status, which directly guides monitoring intensity and treatment location:

Mild DKA

• Venous pH: 7.25-7.30 1, 3
• Serum bicarbonate: 15-18 mEq/L 1, 3
• Anion gap: >10 mEq/L 3
• Mental status: Alert 1, 3

Moderate DKA

• Venous pH: 7.00-7.24 1, 3
• Serum bicarbonate: 10 to <15 mEq/L 1, 3
• Anion gap: >12 mEq/L 3
• Mental status: Alert to drowsy 1, 3

Severe DKA

• Venous pH: <7.00 1, 3
• Serum bicarbonate: <10 mEq/L 1, 3
• Anion gap: >12 mEq/L 3
• Mental status: Stupor or coma 1, 3

Severe DKA requires intensive care monitoring, including central venous and intra-arterial pressure monitoring, with significantly higher morbidity and mortality risk. 1, 3

Essential Laboratory Workup

When DKA is suspected, obtain immediately:

• Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose) 1
• Venous blood gas for pH (arterial pH is not necessary after initial diagnosis) 1
• Blood β-hydroxybutyrate (β-OHB) – this is the gold standard ketone measurement 1, 2
• Anion gap calculation 1
• Serum osmolality 2
• Complete blood count with differential 1, 2
• Urinalysis 1, 2
• Electrocardiogram 2
• Hemoglobin A1C to distinguish acute versus chronic poor control 1
• Bacterial cultures (blood, urine, throat) if infection is suspected 1

Corrected serum sodium should be calculated using: [measured Na (mEq/L)] + [glucose (mg/dL) - 100]/100 × 1.6. 1

Critical Ketone Measurement Considerations

Direct blood β-hydroxybutyrate measurement is mandatory for accurate DKA diagnosis and monitoring – never rely on urine ketone strips or nitroprusside-based tests. 1, 2

• β-OHB is the predominant and strongest ketoacid in DKA 1, 2
• Nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, completely missing β-OHB 1, 2
• During treatment, β-OHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis even as the patient improves 1, 2
• Normal fasting β-OHB is <0.5 mmol/L 1

Euglycemic Diabetic Ketoacidosis (eDKA)

Approximately 10% of DKA presentations are euglycemic, defined by blood glucose <200-250 mg/dL despite meeting acidosis and ketosis criteria. 2, 4

Diagnostic Criteria for eDKA

For euglycemic DKA, diagnosis requires:

• Blood glucose <200-250 mg/dL 2, 4
• Venous pH <7.3 AND serum bicarbonate <18 mEq/L 2
• Elevated blood β-hydroxybutyrate 2
• Either documented hyperglycemia at any prior time OR known history of diabetes 2

Common Precipitating Factors for eDKA

• SGLT2 inhibitor use – the most common modern cause of euglycemic DKA 2, 4, 5
• Reduced caloric intake or prolonged fasting/starvation 2, 4
• Pregnancy 2, 4
• Heavy alcohol consumption 2, 4
• Chronic liver disease 2, 4
• Cocaine abuse 2
• Recent insulin use before presentation 4

Critical Clinical Pitfall

Normal blood glucose levels can masquerade the underlying ketoacidosis, leading to missed or delayed diagnosis. 6, 4 Check blood pH and ketones in all ill diabetic patients regardless of glucose level. 6 Even with euglycemia, the same aggressive treatment with IV fluids and insulin is required, with dextrose added to IV fluids while continuing insulin infusion to clear ketones. 2

Monitoring During Treatment

Blood should be drawn every 2-4 hours to measure:

• Electrolytes (sodium, potassium, chloride) 1
• Glucose 1
• BUN and creatinine 1
• Serum osmolality 1
• Venous pH 1
• Blood β-hydroxybutyrate 1

Venous pH and anion gap adequately monitor acidosis resolution without requiring repeated arterial blood gases. 1 Venous pH is typically 0.03 units lower than arterial pH. 1

Resolution Criteria

DKA is considered resolved when ALL of the following are met:

• Glucose <200 mg/dL 1
• Serum bicarbonate ≥18 mEq/L 1
• Venous pH >7.3 1
• Anion gap ≤12 mEq/L 1
• Blood β-hydroxybutyrate <0.5 mmol/L 1

Ketonemia takes longer to clear than hyperglycemia, requiring continued insulin infusion even after glucose normalizes. 1 Discontinuing insulin prematurely before ketoacidosis resolves leads to recurrence. 1

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis:

• Alcoholic ketoacidosis: Clinical history of alcohol use, glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic, less severe acidosis 2
• Starvation ketosis: Serum bicarbonate typically ≥18 mEq/L, less severe acidosis, prolonged fasting history 1, 2
• Lactic acidosis: Measure blood lactate 1, 2
• Toxic ingestions: Consider salicylates, methanol, ethylene glycol 1, 2
• Chronic renal failure: More commonly produces hyperchloremic acidosis 1, 2