Diagnostic Qualifiers for Diabetic Ketoacidosis (DKA)
DKA is diagnosed when all three of the following criteria are simultaneously present: hyperglycemia (plasma glucose >250 mg/dL), metabolic acidosis (arterial pH <7.3 AND serum bicarbonate <18 mEq/L), and positive ketones in blood or urine. 1
Core Diagnostic Triad
The American Diabetes Association requires all three components to be present concurrently for DKA diagnosis: 1
- Hyperglycemia: Plasma glucose >250 mg/dL 1
- Metabolic acidosis: Arterial pH <7.3 AND serum bicarbonate <18 mEq/L 1
- Ketosis: Positive serum or urine ketones 1
Important Caveat: Euglycemic DKA
- SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA (glucose <250 mg/dL with ketoacidosis), which still requires metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L) and elevated β-hydroxybutyrate for diagnosis 1
- Recent guidelines have de-emphasized the hyperglycemia threshold because of increasing incidence of euglycemic DKA 2
- In euglycemic DKA, the diagnosis relies on the presence of metabolic acidosis and elevated ketones despite glucose <250 mg/dL 1
Severity Stratification
DKA severity is classified based on degree of acidosis, bicarbonate level, anion gap, and mental status: 1
Mild DKA
- Plasma glucose >250 mg/dL 1
- Arterial pH 7.25–7.30 1
- Serum bicarbonate 15–18 mEq/L 1
- Anion gap >10 mEq/L 1, 3
- Mental status: Alert 1
Moderate DKA
- Plasma glucose >250 mg/dL 1
- Arterial pH 7.00–7.24 1
- Serum bicarbonate 10 to <15 mEq/L 1
- Anion gap >12 mEq/L 1, 3
- Mental status: Alert/drowsy 1
Severe DKA
- Plasma glucose >250 mg/dL 1
- Arterial pH <7.00 1
- Serum bicarbonate <10 mEq/L 1
- Anion gap >12 mEq/L 1, 3
- Mental status: Stupor/coma 1
Optimal Ketone Measurement
- Blood β-hydroxybutyrate (βOHB) measurement is the preferred method for diagnosing DKA, not nitroprusside-based tests 1
- Nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, NOT βOHB, which is the predominant ketone in DKA 1
- During treatment, βOHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving 1
- Point-of-care βOHB testing at triage has 98% sensitivity and 85% specificity for DKA diagnosis at the threshold of 1.5 mmol/L 4
Essential Initial Laboratory Workup
When DKA is suspected, obtain: 1
- Plasma glucose 1
- Arterial blood gas (pH, bicarbonate) or venous pH 1
- Serum electrolytes with calculated anion gap 1
- Blood urea nitrogen/creatinine 1
- Serum βOHB (preferred) or serum/urine ketones 1
- Serum osmolality 1
- Complete blood count with differential 1
- Urinalysis 1
- Electrocardiogram 1
Differential Diagnosis Considerations
Alcoholic Ketoacidosis (AKA)
- Distinguished by clinical history of alcohol use with recent cessation 5
- Glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic 1, 5
- High anion gap metabolic acidosis with elevated β-hydroxybutyrate 5
Starvation Ketosis
- Serum bicarbonate usually not lower than 18 mEq/L, distinguishing it from DKA 5, 3
- Less severe acidosis and lower ketone levels compared to DKA 1
Other High Anion Gap Metabolic Acidoses
- DKA must be distinguished from lactic acidosis, salicylate toxicity, methanol or ethylene glycol ingestion, and uremia 3
- The presence of ketones in blood and urine helps differentiate DKA from other causes of anion gap acidosis 3
Resolution Criteria
DKA is considered resolved when all of the following are met: 1
Critical Pitfall: Diabetic Ketoalkalosis
- DKA can present with pH >7.4 (diabetic ketoalkalosis) due to concurrent metabolic alkalosis and/or respiratory alkalosis, yet still have severe ketoacidosis requiring full DKA treatment 6
- In one study, 23.3% of DKA cases presented with pH >7.4, and 34% of these had severe ketoacidosis (βOHB ≥3 mmol/L) 6
- All cases of diabetic ketoalkalosis had increased anion gap metabolic acidosis present despite alkalemic pH 6
- This variant is easily overlooked if clinicians rely solely on pH <7.3 as a diagnostic criterion 6