What are the diagnostic criteria and necessary steps to diagnose Diabetic Ketoacidosis (DKA) in a patient?

Diagnostic Criteria for Diabetic Ketoacidosis (DKA)

To diagnose DKA, you must confirm all three components simultaneously: blood glucose >250 mg/dL (though this threshold is increasingly de-emphasized), venous pH <7.3, serum bicarbonate <15 mEq/L, and elevated blood β-hydroxybutyrate. 1, 2

Core Diagnostic Triad

All three criteria must be present together for DKA diagnosis:

• Hyperglycemia: Blood glucose >250 mg/dL, though recent guidelines have de-emphasized this threshold due to increasing incidence of euglycemic DKA, particularly in patients on SGLT2 inhibitors 1, 3
• Metabolic acidosis: Venous pH <7.3 AND serum bicarbonate <15 mEq/L 1, 2
• Ketosis: Elevated blood β-hydroxybutyrate (β-OHB), which is the preferred and gold standard ketone measurement 1, 4

Critical pitfall: Do NOT rely on urine ketones or nitroprusside-based tests for diagnosis—these only measure acetoacetate and acetone, completely missing β-hydroxybutyrate, which is the predominant and strongest ketoacid in DKA. 1, 4 During treatment, β-OHB converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves. 2

Essential Initial Laboratory Workup

Obtain immediately upon suspicion of DKA:

• Complete metabolic panel: Sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose 1, 2
• Venous blood gas: pH, pCO2, bicarbonate (arterial blood gas is NOT necessary after initial diagnosis) 2
• Blood β-hydroxybutyrate: Direct measurement, not urine ketones 1, 4
• Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), should be >10-12 mEq/L in DKA 1, 2
• Complete blood count with differential 5, 1
• Urinalysis with urine ketones by dipstick (for initial screening only, not for monitoring) 5
• Serum osmolality 5, 1
• Electrocardiogram 5, 1
• HbA1c: Useful to determine if this is an acute episode in a well-controlled patient versus culmination of poor control 5

Additional Testing When Indicated

• Bacterial cultures (blood, urine, throat) and appropriate antibiotics if infection is suspected as precipitating factor 5, 2
• Chest X-ray if respiratory symptoms or infection suspected 5
• Amylase, lipase, hepatic transaminases, troponin, creatine kinase to identify complications or precipitating causes 3

Severity Classification

DKA severity determines monitoring intensity and prognosis:

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, anion gap >10, alert mental status 1, 2
• Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, anion gap >12, drowsy/lethargic mental status 1, 2
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, anion gap >12, stuporous or comatose mental status—associated with higher morbidity and mortality, often requiring central venous and intra-arterial pressure monitoring 1, 2

Critical Differential Diagnosis Considerations

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

• Lactic acidosis: Measure blood lactate 1
• Alcoholic ketoacidosis (AKA): Distinguished by clinical history and plasma glucose that ranges from mildly elevated (rarely >250 mg/dL) to hypoglycemia; serum bicarbonate in starvation ketosis usually not lower than 18 mEq/L 5, 1
• Toxic ingestions: Salicylate, methanol, ethylene glycol, paraldehyde—identified by specific laboratory tests and clinical presentation 5, 1
• Chronic renal failure: More typically hyperchloremic acidosis rather than high anion gap acidosis 5

Clinical Presentation Features to Recognize

History findings: Polyuria, polydipsia, weight loss, vomiting, abdominal pain, weakness, altered mental status 1, 3

Physical examination findings: Poor skin turgor, Kussmaul respirations (deep, rapid breathing), tachycardia, hypotension, fruity breath odor (acetone), altered mental status 1

Important caveat: Patients can be normothermic or even hypothermic despite infection as precipitating factor due to peripheral vasodilation; hypothermia is a poor prognostic sign. 5 Up to 25% may have coffee-ground emesis due to hemorrhagic gastritis. 1

Euglycemic DKA Recognition

Do NOT dismiss DKA possibility because glucose is <250 mg/dL—euglycemic DKA is increasingly common, especially with SGLT2 inhibitors, pregnancy, recent insulin use, decreased caloric intake, or heavy alcohol consumption. 4, 3, 6 The diagnosis still requires metabolic acidosis and elevated ketones even when glucose is normal or only mildly elevated.

Monitoring During Treatment

Once DKA is diagnosed, draw blood every 2-4 hours to measure:

• Electrolytes (sodium, potassium, chloride, bicarbonate) 1, 2
• Glucose 1, 2
• Venous pH (NOT arterial—venous pH typically 0.03 units lower than arterial and suffices for monitoring) 2
• β-hydroxybutyrate 1, 2
• Anion gap 1, 2
• BUN/creatinine 1, 2
• Serum osmolality 1, 2

Resolution Criteria

DKA is resolved when ALL of the following are met:

• Glucose <200 mg/dL 1, 2
• Venous pH >7.3 1, 2
• Serum bicarbonate ≥18 mEq/L 1, 2
• Anion gap ≤12 mEq/L 1, 2

Critical monitoring pitfall: Ketonemia typically takes longer to clear than hyperglycemia—continue monitoring β-hydroxybutyrate and insulin therapy even after glucose normalizes to prevent recurrence. 1, 2