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

Diagnosing Diabetic Ketoacidosis (DKA)

DKA is diagnosed by the triad of hyperglycemia (blood glucose >250 mg/dL), metabolic acidosis (venous pH <7.3 and serum bicarbonate <15 mEq/L), and elevated blood ketones, preferably measured as β-hydroxybutyrate. 1

Core Diagnostic Criteria

The American Diabetes Association establishes that all three components must be present simultaneously for DKA diagnosis 1, 2:

• Blood glucose >250 mg/dL - though this threshold has been de-emphasized in recent guidelines due to increasing incidence of euglycemic DKA, particularly in patients on SGLT2 inhibitors 2, 3
• Venous pH <7.3 - this reflects the severity of ketoacidosis and is required for diagnosis 1, 2
• Serum bicarbonate <15 mEq/L - indicates metabolic acidosis 1, 2
• Elevated blood β-hydroxybutyrate (β-OHB) - the preferred ketone measurement 1, 2

Essential Laboratory Workup

Upon presentation, immediately obtain 1, 2:

• Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose)
• Venous blood gas (pH, pCO2, bicarbonate)
• Blood β-hydroxybutyrate - this is the gold standard, NOT urine ketones
• Complete blood count with differential
• Urinalysis
• Serum osmolality
• Electrocardiogram
• Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]) - should be >10-12 mEq/L in DKA 1, 2

Severity Classification

DKA severity determines monitoring intensity and prognosis 4, 1:

• Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L, anion gap >10, alert mental status 4, 1
• Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L, anion gap >12, drowsy/lethargic 4, 1
• Severe DKA: pH <7.00, bicarbonate <10 mEq/L, anion gap >12, stuporous or comatose - associated with higher morbidity and mortality, often requiring central venous and intra-arterial pressure monitoring 4, 1

Critical Ketone Measurement Considerations

Use direct blood β-hydroxybutyrate measurement, NOT urine ketones or nitroprusside-based tests 1, 2, 5. This is a crucial diagnostic pitfall:

• The nitroprusside method (used in urine dipsticks and some serum tests) only measures acetoacetate and acetone, completely missing β-OHB, which is the predominant and strongest ketoacid in DKA 1, 2
• During treatment, β-OHB is converted to acetoacetate, which paradoxically makes nitroprusside tests appear worse even as the patient improves 1
• Blood β-OHB can be measured at point-of-care using a meter within minutes 5

Special Diagnostic Considerations

Euglycemic DKA

Do not dismiss DKA possibility because glucose is <250 mg/dL 2, 3:

• SGLT2 inhibitors significantly increase risk of euglycemic DKA (glucose <250 mg/dL with ketoacidosis) 2, 3
• This variant is increasingly common and requires the same diagnostic approach 2

Diabetic Ketoalkalosis

DKA can present with pH >7.3 or bicarbonate >18 mEq/L when complicated by mixed acid-base disorders 6:

• 23% of DKA cases present with pH >7.4 (diabetic ketoalkalosis) due to concurrent metabolic or respiratory alkalosis 6
• These patients still have increased anion gap metabolic acidosis and elevated β-OHB, and 34% have severe ketoacidosis requiring the same treatment as traditional DKA 6
• Always calculate the anion gap and measure β-OHB even when pH appears normal or alkalemic 6

Corrected Sodium Calculation

Correct serum sodium for hyperglycemia using the formula: [measured Na (mEq/L)] + [glucose (mg/dL) - 100]/100 × 1.6 1. This provides a more accurate assessment of true sodium status and guides fluid therapy 1.

Differential Diagnosis

DKA must be distinguished from other causes of high anion gap metabolic acidosis 4:

• Lactic acidosis - measure blood lactate
• Toxic ingestions - salicylate, methanol, ethylene glycol (look for calcium oxalate crystals in urine), paraldehyde (characteristic breath odor)
• Chronic renal failure - typically causes hyperchloremic acidosis
• Metformin use - obtain history and measure lactate

Clinical Presentation

The classical presentation includes 4:

• History: polyuria, polydipsia, weight loss, vomiting, abdominal pain (specific to DKA, not HHS), weakness, altered mental status
• Physical findings: poor skin turgor, Kussmaul respirations (deep, rapid breathing), tachycardia, hypotension, fruity breath odor, altered mental status ranging from alert to comatose 4, 7
• Up to 25% have coffee-ground emesis due to hemorrhagic gastritis 4
• Patients can be normothermic or hypothermic despite infection; hypothermia is a poor prognostic sign 4

Monitoring During Treatment

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

• Electrolytes (sodium, potassium, chloride, bicarbonate)
• Glucose
• Venous pH (arterial blood gases are unnecessary after initial diagnosis) 1
• β-hydroxybutyrate
• Anion gap
• BUN/creatinine
• Serum osmolality

Resolution Criteria

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

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

Ketonemia typically takes longer to clear than hyperglycemia, requiring continued monitoring and insulin therapy even after glucose normalizes 1.

Common Diagnostic Pitfalls to Avoid

• Never rely solely on urine ketones for diagnosis or monitoring - they miss β-OHB and can be falsely negative early in DKA 1, 2
• Do not repeat arterial blood gases unnecessarily - venous pH suffices for monitoring after initial diagnosis 1
• Always consider infection as a precipitating factor - obtain bacterial cultures of urine, blood, and throat if suspected, even though patients may be normothermic 4, 1
• Recognize that DKA occurs in type 2 diabetes - use the same diagnostic criteria 2