What labs should be drawn to diagnose diabetic ketoacidosis (DKA)?

Laboratory Evaluation for Diabetic Ketoacidosis (DKA)

Draw plasma glucose, serum electrolytes with calculated anion gap, serum bicarbonate, blood urea nitrogen/creatinine, arterial or venous blood gas, serum beta-hydroxybutyrate (β-OHB), urinalysis with urine ketones, complete blood count with differential, and electrocardiogram immediately upon presentation. 1, 2

Essential Initial Laboratory Tests

Core Diagnostic Parameters

The diagnosis of DKA requires three specific laboratory findings that must all be present 1, 2:

• Plasma glucose >250 mg/dL (though euglycemic DKA can occur, particularly with SGLT2 inhibitor use) 1, 2, 3
• Arterial pH <7.3 or venous pH <7.3 (venous pH is typically 0.03 units lower than arterial and is sufficient for diagnosis) 1, 2, 4
• Serum bicarbonate <15 mEq/L 1, 2
• Moderate ketonuria or ketonemia (preferably measured as β-OHB) 1, 2

Metabolic Panel Components

Order a complete metabolic panel that includes 1, 2:

• Serum sodium - must be corrected for hyperglycemia using the formula: measured Na (mEq/L) + [glucose (mg/dL) - 100]/100 × 1.6 2
• Serum potassium - critical before starting insulin therapy; if <3.3 mEq/L, delay insulin and replace potassium aggressively first 2
• Serum chloride - needed to calculate anion gap 1, 2
• Blood urea nitrogen and creatinine - assess renal function and hydration status 1, 2
• Serum osmolality - helps differentiate from hyperosmolar hyperglycemic state 1, 2

Anion Gap Calculation

Calculate the anion gap using the formula: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), which should be >10-12 mEq/L in DKA 2. This confirms the presence of high anion gap metabolic acidosis, a hallmark of DKA 1, 5.

Ketone Measurement: Critical Distinction

Preferred Method

Measure serum beta-hydroxybutyrate (β-OHB) directly - this is the gold standard for both diagnosis and monitoring of DKA 1, 2, 4. β-OHB is the predominant ketone body in DKA and provides the most accurate assessment 1.

Methods to Avoid

Do not rely on nitroprusside-based tests (urine ketones or serum ketone dipsticks) for diagnosis or monitoring 1, 2. These tests only measure acetoacetate and acetone, completely missing β-OHB 1. During treatment, β-OHB converts to acetoacetate, which paradoxically makes nitroprusside tests appear worse even as the patient improves 2, 4.

If β-OHB measurement is unavailable, positive nitroprusside-based ketone tests combined with hyperglycemia and metabolic acidosis can confirm DKA, but should not be used for treatment monitoring 1.

Additional Essential Tests

Blood Gas Analysis

• Arterial or venous blood gas - venous pH is adequate for initial diagnosis and subsequent monitoring 1, 2, 4
• After initial diagnosis, repeat arterial blood gases are generally unnecessary; venous pH and anion gap adequately monitor acidosis resolution 2, 4

Infection Workup

If infection is suspected as a precipitating factor, obtain 1, 2:

• Blood cultures
• Urine cultures
• Throat cultures
• Chest X-ray (if respiratory symptoms present) 1

Additional Markers

• Complete blood count with differential - leukocytosis is common even without infection 1, 2
• Electrocardiogram - assess for cardiac complications and monitor for hyperkalemia or hypokalemia changes 1, 2
• HbA1c - helps determine if this represents poorly controlled chronic diabetes or an acute event in a well-controlled patient 1

Monitoring During Treatment

Draw blood every 2-4 hours during active treatment to measure 2, 4:

• Serum electrolytes (sodium, potassium, chloride, bicarbonate)
• Plasma glucose
• Blood urea nitrogen and creatinine
• Serum osmolality
• Venous pH
• Beta-hydroxybutyrate (if available) 2, 4

Continue this frequent monitoring until the patient is stable and DKA has resolved 2, 4.

Resolution Criteria

DKA is considered resolved when all of the following are met 2, 4:

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

Common Pitfalls to Avoid

• Do not rely solely on urine ketones - they are inadequate for diagnosis and misleading for monitoring 1, 2
• Do not overlook euglycemic DKA - particularly in patients on SGLT2 inhibitors, where glucose may be <250 mg/dL despite severe ketoacidosis 1, 3
• Do not start insulin if potassium <3.3 mEq/L - this can precipitate fatal cardiac arrhythmias 2
• Do not repeat arterial blood gases unnecessarily - venous pH suffices after initial diagnosis 2, 4
• Do not ignore mixed acid-base disorders - approximately 23% of DKA cases present with alkalemia (pH >7.4) due to concurrent metabolic or respiratory alkalosis, yet still require full DKA treatment 6