What are the diagnostic criteria for diabetic ketoacidosis in a patient with diabetes?

Diagnosis of Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three of the following criteria are simultaneously present: hyperglycemia (plasma glucose >250 mg/dL), metabolic acidosis (arterial or venous pH <7.3 AND serum bicarbonate <18 mEq/L), and ketosis (positive serum or urine ketones, preferably measured as blood β-hydroxybutyrate). 1, 2

Core Diagnostic Criteria

All three components must be present to confirm DKA:

• Hyperglycemia: Plasma glucose >250 mg/dL 1, 2, 3
• Metabolic acidosis: Arterial pH <7.3 AND serum bicarbonate <18 mEq/L 1, 2, 3
• Ketosis: Positive ketones in blood or urine 1, 2

The simultaneous presence of all three criteria is mandatory—meeting only one or two does not establish the diagnosis. 2

Essential Initial Laboratory Workup

When DKA is suspected, obtain the following tests immediately:

• Plasma glucose 2
• Arterial or venous blood gas for pH and bicarbonate 2
• Serum electrolytes with calculated anion gap (anion gap = [Na⁺] - [Cl⁻ + HCO₃⁻]; should be >10 mEq/L in DKA) 2, 3
• Blood β-hydroxybutyrate (preferred ketone measurement) 2, 3
• Blood urea nitrogen and creatinine 2
• Serum osmolality 2
• Complete blood count with differential 2
• Urinalysis 2
• Electrocardiogram 2

Critical Ketone Measurement: β-Hydroxybutyrate

Blood β-hydroxybutyrate (β-OHB) measurement is the preferred method for diagnosing and monitoring DKA, not nitroprusside-based urine or serum tests. 1, 2, 3

• β-OHB is the predominant ketone body in DKA and the strongest acid; nitroprusside-based tests (urine dipsticks, serum tablets) only detect acetoacetate and acetone, completely missing β-OHB. 2, 3
• Normal fasting β-OHB is <0.5 mmol/L; elevated levels confirm ketosis. 3
• During treatment, β-OHB converts to acetoacetate, which paradoxically makes nitroprusside tests appear worse even as the patient improves—a critical pitfall. 2, 3

Severity Classification

DKA severity is stratified based on the degree of acidosis and mental status:

• Mild DKA: Arterial pH 7.25–7.30, bicarbonate 15–18 mEq/L, anion gap >10 mEq/L, alert mental status 2, 3
• Moderate DKA: Arterial pH 7.00–7.24, bicarbonate 10–<15 mEq/L, anion gap >12 mEq/L, alert to drowsy mental status 2, 3
• Severe DKA: Arterial pH <7.00, bicarbonate <10 mEq/L, anion gap >12 mEq/L, stupor or coma 2, 3

Severe DKA is associated with higher morbidity and mortality and often requires intensive monitoring, including central venous and intra-arterial pressure monitoring. 3

Euglycemic Diabetic Ketoacidosis (eDKA)

Approximately 10% of DKA presentations are euglycemic, defined by plasma glucose <200 mg/dL despite meeting the other DKA criteria. 1, 2

• For eDKA, diagnosis requires either documented hyperglycemia at any point or a prior history of diabetes, in addition to metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L) and elevated β-hydroxybutyrate. 1, 2
• Common precipitating factors for eDKA include:
  • SGLT2 inhibitor therapy (most frequent modern cause) 1, 2
  • Reduced caloric intake or prolonged fasting 1, 2
  • Pregnancy 1, 2, 4
  • Alcohol consumption 1, 2, 4
  • Chronic liver disease 1, 2, 4

Recognition of eDKA is crucial—if only the serum glucose level is considered while ignoring ketone levels and acid-base status, the diagnosis will be missed. 5, 4

Differential Diagnosis

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

• Alcoholic ketoacidosis (AKA): Clinical history of alcohol use, glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic, less severe acidosis than DKA 2
• Starvation ketosis: Serum bicarbonate typically ≥18 mEq/L, less severe acidosis, prolonged fasting history 2
• Lactic acidosis: Elevated blood lactate 2
• Toxic ingestions: Salicylates, methanol, ethylene glycol 2

Resolution Criteria

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

• Glucose <200 mg/dL 2, 3
• Serum bicarbonate ≥18 mEq/L 2, 3
• Venous pH >7.3 2, 3
• Anion gap ≤12 mEq/L 3

Continue monitoring β-hydroxybutyrate until it normalizes (<0.5 mmol/L), as ketone clearance typically takes longer than glucose normalization. 2, 3

Common Diagnostic Pitfalls to Avoid

• Do not rely on urine ketones or nitroprusside-based tests for diagnosis or monitoring—they miss β-OHB and can falsely suggest worsening ketosis during treatment. 2, 3
• Do not dismiss the diagnosis in patients with normal or mildly elevated glucose—always check ketones and acid-base status in diabetic patients presenting with metabolic acidosis. 1, 5, 4
• After initial diagnosis, venous pH and anion gap adequately monitor acidosis resolution—repeated arterial blood gases are generally unnecessary. 2, 3