How do you diagnose diabetic ketoacidosis (DKA) in a patient?

How to Diagnose Diabetic Ketoacidosis (DKA)

DKA is diagnosed when all three biochemical criteria are present simultaneously: blood glucose >250 mg/dL, venous pH <7.3, and serum bicarbonate <15 mEq/L, along with elevated blood ketones (preferably β-hydroxybutyrate). 1, 2

Core Diagnostic Criteria

You need all three of these parameters present at the same time to diagnose DKA 1, 2:

• Blood glucose >250 mg/dL (though this threshold is less emphasized now due to euglycemic DKA, particularly in patients on SGLT2 inhibitors) 2
• Venous pH <7.3 (reflects severity of ketoacidosis) 3, 1, 2
• Serum bicarbonate <15 mEq/L (indicates metabolic acidosis) 3, 1, 2
• Elevated blood β-hydroxybutyrate (the preferred ketone measurement—not urine ketones) 1, 2

Important caveat: About 23% of DKA cases present with pH >7.4 (diabetic ketoalkalosis) due to mixed acid-base disorders, yet still have severe ketoacidosis requiring full DKA treatment. 4 Don't be fooled by a normal or alkalemic pH if the patient has hyperglycemia, elevated anion gap, and positive ketones.

Essential Laboratory Workup

Order these tests immediately when DKA is suspected 1, 2:

• Complete metabolic panel (sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose) 1
• Venous blood gas (pH, pCO2, bicarbonate)—arterial blood gas is unnecessary for diagnosis or monitoring 1
• Blood β-hydroxybutyrate (gold standard—do NOT rely on urine ketones or nitroprusside tests, as they miss β-hydroxybutyrate, the predominant ketoacid) 1, 2
• Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]) should be >10-12 mEq/L 1, 2
• Complete blood count with differential 1
• Urinalysis 1
• Serum osmolality 1
• Electrocardiogram 1

If infection is suspected as a precipitating factor, obtain bacterial cultures of urine, blood, and throat. 1

Clinical Presentation to Look For

Classic symptoms evolving over <24 hours (though can be longer) 3:

• Polyuria, polydipsia, weight loss 3, 2
• Nausea, vomiting (up to 25% have coffee-ground emesis from hemorrhagic gastritis) 3, 2
• Abdominal pain (specific to DKA, not HHS) 3
• Weakness, severe fatigue 3

Physical examination findings 3, 2:

• Kussmaul respirations (deep, rapid breathing) 3
• Poor skin turgor (dehydration) 3
• Fruity breath odor (acetone) 2
• Tachycardia, hypotension 3
• Altered mental status ranging from full alertness to lethargy or coma 3, 2
• Patients can be normothermic or hypothermic despite infection (hypothermia is a poor prognostic sign) 3

Severity Classification

Once diagnosed, classify severity to guide monitoring intensity 1, 2:

Mild DKA: 1, 2

• pH 7.25-7.30
• Bicarbonate 15-18 mEq/L
• Anion gap >10
• Alert mental status

Moderate DKA: 1, 2

• pH 7.00-7.24
• Bicarbonate 10-15 mEq/L
• Anion gap >12
• Drowsy/lethargic

Severe DKA: 1, 2

• pH <7.00
• Bicarbonate <10 mEq/L
• Anion gap >12
• Stuporous or comatose
• Higher morbidity and mortality, may require central venous and intra-arterial pressure monitoring 1

Critical Diagnostic Pitfalls to Avoid

Do NOT use urine ketones or nitroprusside-based tests for diagnosis or monitoring. 1, 2 These only measure acetoacetate and acetone, completely missing β-hydroxybutyrate (the predominant ketoacid). During treatment, β-hydroxybutyrate converts to acetoacetate, making these tests paradoxically appear worse even as the patient improves. 1

Don't dismiss DKA if glucose is <250 mg/dL. Euglycemic DKA is increasingly common, especially with SGLT2 inhibitor use. 2, 5 If the patient has acidosis, elevated anion gap, and positive β-hydroxybutyrate, treat as DKA regardless of glucose level.

Venous pH is sufficient—you don't need arterial blood gases for diagnosis or monitoring (venous pH is typically 0.03 units lower than arterial). 1, 6

Differential Diagnosis

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

• Lactic acidosis (measure blood lactate) 2
• Toxic ingestions (salicylate, methanol, ethylene glycol—check specific labs and clinical context) 2
• Chronic renal failure 2
• Metformin use 2

Also differentiate from conditions with overlapping symptoms: pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen, and CNS infection. 7