What are the diagnostic criteria and treatment guidelines for Diabetic Ketoacidosis (DKA)?

Diagnostic Criteria for Diabetic Ketoacidosis (DKA)

The American Diabetes Association requires all three components to be present simultaneously for DKA diagnosis: blood glucose >250 mg/dL, venous pH <7.3, and serum bicarbonate <15 mEq/L, with elevated blood ketones (preferably β-hydroxybutyrate). 1, 2

Core Diagnostic Parameters

The diagnosis of DKA mandates the simultaneous presence of three key elements 2:

• Hyperglycemia: Blood glucose >250 mg/dL, though this threshold is increasingly de-emphasized due to euglycemic DKA (particularly with SGLT2 inhibitors) 2, 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 gold standard measurement 1, 2, 3

Essential Laboratory Workup

Upon presentation with suspected DKA, immediately obtain 1, 2:

• Complete metabolic panel including sodium, potassium, chloride, bicarbonate, BUN, creatinine, and glucose 2
• Venous blood gas with pH, pCO2, and bicarbonate 2
• Blood β-hydroxybutyrate (NOT urine ketones or nitroprusside tests) 1, 2, 3
• Complete blood count with differential 2
• Urinalysis 2
• Serum osmolality 2
• Electrocardiogram 2
• Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]), which should be >10-12 mEq/L in DKA 1, 2
• Bacterial cultures (urine, blood, throat) if infection is suspected 1

Severity Classification

DKA severity determines monitoring intensity and prognosis 1, 2:

Mild DKA

• Venous pH: 7.25-7.30 1, 2
• Bicarbonate: 15-18 mEq/L 1, 2
• Anion gap: >10 mEq/L 2
• Mental status: Alert 1, 2

Moderate DKA

• Venous pH: 7.00-7.24 1, 2
• Bicarbonate: 10-15 mEq/L 1, 2
• Anion gap: >12 mEq/L 2
• Mental status: Drowsy/lethargic 1, 2

Severe DKA

• Venous pH: <7.00 1, 2
• Bicarbonate: <10 mEq/L 1, 2
• Anion gap: >12 mEq/L 2
• Mental status: Stuporous or comatose 1, 2
• Associated with higher morbidity and mortality, often requiring intensive monitoring including central venous and intra-arterial pressure monitoring 1

Critical Ketone Measurement Considerations

Direct blood β-hydroxybutyrate (β-OHB) measurement is mandatory—do NOT rely on urine ketones or nitroprusside-based tests. 1, 2, 3

The nitroprusside method has critical limitations 1, 2:

• Only measures acetoacetate and acetone, completely missing β-OHB (the predominant and strongest ketoacid in DKA) 1, 2
• During treatment, β-OHB converts to acetoacetate, paradoxically making nitroprusside tests appear worse even as the patient improves 1
• Can be falsely negative early in DKA 3

Special Diagnostic Considerations

Euglycemic DKA

• Increasingly common, particularly with SGLT2 inhibitors 2, 3
• Do not dismiss DKA possibility when glucose is <250 mg/dL 3
• All other diagnostic criteria (pH, bicarbonate, ketones) must still be met 2

Diabetic Ketoalkalosis

• DKA can present with pH >7.4 due to concurrent metabolic alkalosis and/or respiratory alkalosis 4
• Increased anion gap metabolic acidosis is still present in all cases 4
• 34% of these cases have severe ketoacidosis (β-OHB ≥3 mmol/L) requiring the same treatment as traditional DKA 4

Type 2 Diabetes

• Use identical diagnostic criteria as type 1 diabetes 3
• DKA is less common but can occur, especially with SGLT2 inhibitors 3

Differential Diagnosis

DKA must be distinguished from 2:

• Lactic acidosis: Measure blood lactate 2
• Toxic ingestions: Salicylate, methanol, ethylene glycol—obtain specific laboratory tests 2
• Chronic renal failure: Assess renal function 1
• Alcoholic ketoacidosis: Clinical history and glucose levels typically lower 1
• Starvation ketosis: Bicarbonate levels typically higher 1

Monitoring During Treatment

Draw blood every 2-4 hours to measure 1, 2:

• Electrolytes (sodium, potassium, chloride) 1
• Glucose 1
• Venous pH 1
• β-hydroxybutyrate 1
• Anion gap 1
• BUN/creatinine 1
• Serum osmolality 1

After initial diagnosis, venous pH and anion gap adequately monitor acidosis resolution—repeated arterial blood gases are unnecessary. 1

Resolution Criteria

DKA is resolved when ALL of the following are met 1, 2:

• 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

Ketonemia typically takes longer to clear than hyperglycemia—continue monitoring and insulin therapy even after glucose normalizes. 1, 2

Common Diagnostic Pitfalls to Avoid

• Never rely solely on urine ketones for diagnosis or monitoring, as they miss β-OHB and provide misleading information during treatment 1, 3
• Do not dismiss DKA when glucose is <250 mg/dL, especially in patients on SGLT2 inhibitors 3
• Avoid repeating arterial blood gases unnecessarily after initial diagnosis—venous pH suffices for monitoring 1
• Do not stop monitoring ketones when glucose normalizes, as ketoacidosis resolution lags behind glycemic correction 1, 2