What laboratory tests confirm diabetic ketoacidosis (DKA) in a patient with a history of diabetes?

Laboratory Confirmation of Diabetic Ketoacidosis

The diagnosis of DKA requires three simultaneous laboratory findings: blood glucose >250 mg/dL (though euglycemic DKA with glucose <250 mg/dL is increasingly recognized), venous pH <7.3, serum bicarbonate <15 mEq/L, and elevated blood β-hydroxybutyrate (the preferred ketone measurement). 1, 2

Essential Diagnostic Laboratory Tests

The American Diabetes Association recommends obtaining the following tests immediately when DKA is suspected 3, 4:

Core Diagnostic Parameters

• Blood glucose: Typically >250 mg/dL in classic DKA, though euglycemic DKA (glucose <250 mg/dL) occurs with SGLT2 inhibitors, pregnancy, reduced caloric intake, or ketogenic diets 1, 2, 5
• Venous pH: Must be <7.3 for diagnosis (venous sampling is sufficient; arterial puncture is unnecessary) 1, 2
• Serum bicarbonate: Must be <15 mEq/L to meet DKA criteria 1, 4
• Blood β-hydroxybutyrate (β-OHB): The preferred and most accurate ketone measurement for both diagnosis and monitoring; levels ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults confirm DKA 3, 1, 6

Critical Supporting Tests

• Anion gap: Calculate as [Na⁺] - ([Cl⁻] + [HCO₃⁻]); should be >10-12 mEq/L in DKA to confirm high anion gap metabolic acidosis 1, 4, 2
• Serum electrolytes: Essential for calculating anion gap and corrected sodium (add 1.6 mEq/L for every 100 mg/dL glucose above 100) 3, 4, 2
• Serum potassium: Critical measurement before starting insulin therapy, as insulin drives potassium intracellularly and can cause life-threatening hypokalemia 4, 2
• Blood urea nitrogen and creatinine: Assess renal function and hydration status 3, 4
• Serum osmolality: Evaluate hyperosmolar state 3, 4

Additional Diagnostic Tests

• Complete blood count with differential: Identify infection as precipitating cause 3, 4
• Urinalysis with urine ketone dipstick: Screen for infection and ketonuria, though less reliable than blood ketones 3, 4
• Electrocardiogram: Detect cardiac complications and potassium-related arrhythmias 3, 4
• HbA1c: Distinguish acute decompensation in well-controlled diabetes from chronic poor control 3, 4
• Bacterial cultures (blood, urine, throat): Obtain if infection suspected 3, 1

Severity Classification Based on Laboratory Values

Once DKA is confirmed, severity is classified as follows 1, 4:

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert mental status
• Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy/lethargic
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, stuporous or comatose (requires intensive monitoring)

Critical Pitfalls to Avoid

Never use nitroprusside-based ketone tests (urine or serum) for diagnosis or monitoring DKA treatment. These tests only measure acetoacetate and acetone, completely missing β-hydroxybutyrate—the predominant ketoacid in DKA. During treatment, β-hydroxybutyrate converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves 3, 1.

Do not delay insulin therapy if initial potassium is <3.3 mEq/L—instead, aggressively replace potassium first to prevent fatal cardiac arrhythmias 4, 2.

Do not dismiss DKA if glucose is <250 mg/dL. Euglycemic DKA is increasingly common with SGLT2 inhibitors and requires the same diagnostic approach focusing on acidosis and ketones 2, 5, 7.

Do not assume normal temperature rules out infection—patients with DKA can be normothermic or even hypothermic despite serious infection, and hypothermia is a poor prognostic sign 3, 4.

Monitoring During Treatment

Repeat laboratory tests every 2-4 hours during treatment 1, 4:

• Electrolytes, glucose, BUN, creatinine
• Venous pH (arterial blood gases are unnecessary after initial diagnosis; venous pH is typically 0.03 units lower than arterial) 1, 2
• β-hydroxybutyrate (continues until normalized, even after urine ketones clear)
• Anion gap

Resolution Criteria

DKA is resolved when all of the following are present 1, 4, 2:

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

Note that ketonemia clears more slowly than hyperglycemia, so β-hydroxybutyrate may remain elevated even after other parameters normalize 1, 2.

Differential Diagnosis Considerations

Distinguish DKA from other causes of high anion gap metabolic acidosis 3, 2:

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