How is glycemic diabetic ketoacidosis diagnosed?

How to Diagnose Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three 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 positive ketones in blood or urine, with blood β-hydroxybutyrate being the preferred measurement method. 1

Core Diagnostic Triad

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

• Hyperglycemia: Plasma glucose >250 mg/dL 2, 1
• Metabolic acidosis: Arterial pH <7.3 AND serum bicarbonate <18 mEq/L 2, 1
• Ketosis: Positive serum or urine ketones, preferably measured as blood β-hydroxybutyrate 1

Critical caveat: Approximately 10% of DKA cases present as euglycemic DKA (glucose <200 mg/dL), which requires either documented hyperglycemia at any point OR a prior history of diabetes, plus the metabolic acidosis and ketosis criteria. 2, 1

Essential Initial Laboratory Workup

When DKA is suspected, immediately obtain:

• Plasma glucose 1
• Arterial or venous blood gas for pH and bicarbonate (venous pH is typically 0.03 units lower than arterial and is adequate for diagnosis) 3
• Serum electrolytes with calculated anion gap using [Na⁺] - ([Cl⁻] + [HCO₃⁻]); anion gap should be >10 mEq/L in DKA 1, 3
• Blood β-hydroxybutyrate (preferred over nitroprusside-based tests) 1, 3
• Blood urea nitrogen and creatinine 1
• Serum osmolality 1
• Complete blood count with differential 1
• Urinalysis 1
• Electrocardiogram 1

Preferred Ketone Measurement Method

Blood β-hydroxybutyrate is the gold standard for diagnosing and monitoring DKA. 1, 3

• β-hydroxybutyrate is the predominant ketone body in DKA and the strongest acid 1
• Normal fasting ketone levels are <0.5 mmol/L 3
• Do NOT rely on nitroprusside-based urine dipsticks or serum tablets because they only detect acetoacetate and acetone, completely missing β-hydroxybutyrate 1, 3
• During treatment, β-hydroxybutyrate converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving 1, 3

Severity Classification

Once DKA is diagnosed, stratify severity based on acidosis degree and mental status:

• Mild DKA: pH 7.25–7.30, bicarbonate 15–18 mEq/L, anion gap >10 mEq/L, alert mental status 1
• Moderate DKA: pH 7.00–7.24, bicarbonate 10 to <15 mEq/L, anion gap >12 mEq/L, alert to drowsy mental status 1
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, anion gap >12 mEq/L, stupor or coma 1, 3

Euglycemic DKA: Special Diagnostic Considerations

Euglycemic DKA is diagnosed when glucose is <200–250 mg/dL but metabolic acidosis and elevated ketones are present. 1

For euglycemic DKA diagnosis, you need:

• Either documented hyperglycemia at any point OR a prior history of diabetes 2, 1
• Metabolic acidosis: pH <7.3 AND bicarbonate <18 mEq/L 1
• Elevated blood β-hydroxybutyrate 1

Common precipitating factors for euglycemic DKA include:

• SGLT2 inhibitor therapy (most frequent modern cause) 2, 1
• Reduced caloric intake or prolonged fasting 2, 1
• Pregnancy 2, 1
• Alcohol consumption 2, 1
• Chronic liver disease 2, 1

Critical Differential Diagnoses

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

• Alcoholic ketoacidosis (AKA): Clinical history of alcohol abuse with recent cessation, glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic, elevated β-hydroxybutyrate 1, 4
• Starvation ketosis: Serum bicarbonate typically ≥18 mEq/L, less severe acidosis than DKA, prolonged fasting history 1
• Lactic acidosis 1
• Toxic ingestions (salicylates, methanol, ethylene glycol) 1

Resolution Criteria

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

• Glucose <200 mg/dL 1, 3
• Serum bicarbonate ≥18 mEq/L 1, 3
• Venous pH >7.3 1, 3
• Anion gap ≤12 mEq/L 3
• β-hydroxybutyrate normalized to <0.5 mmol/L 3

Common Diagnostic Pitfalls to Avoid

• Do not dismiss DKA based on normal glucose levels alone—always check ketones and pH in any diabetic patient with suspected metabolic decompensation 1, 5
• Never use urine ketone strips or nitroprusside tests as your primary diagnostic tool—they miss β-hydroxybutyrate and can be misleading during treatment 1, 3
• Do not assume infection is present based on leukocytosis alone—DKA itself causes elevated white blood cell counts 2
• Remember that patients can be normothermic or hypothermic despite infection—hypothermia is a poor prognostic sign 2