Diagnosing Diabetic Ketoacidosis (DKA)
DKA is diagnosed when all three 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 present at the same time for diagnosis 1, 2:
- Hyperglycemia: Blood glucose >250 mg/dL 1, 3, 2
- Metabolic acidosis: Venous pH <7.3 AND serum bicarbonate <15-18 mEq/L 1, 3, 2
- Ketosis: Elevated blood ketones (preferably β-hydroxybutyrate) 1, 2
Critical Laboratory Workup
When DKA is suspected, immediately obtain 2:
- Plasma glucose 1
- Arterial or venous blood gas (pH, bicarbonate) 1, 2
- Serum electrolytes with calculated anion gap (>10 mEq/L in mild DKA, >12 mEq/L in moderate/severe) 1
- Blood β-hydroxybutyrate (β-OHB) - this is the preferred ketone measurement 1, 2
- Blood urea nitrogen/creatinine 1
- Serum osmolality 1, 2
- Complete blood count with differential 1, 2
- Urinalysis 1, 2
- Electrocardiogram 1, 2
Ketone Measurement: Critical Technical Point
The American Diabetes Association recommends blood β-hydroxybutyrate (β-OHB) measurement as the preferred method for diagnosing DKA, NOT nitroprusside-based tests. 1
This distinction is crucial because 1, 2:
- Nitroprusside methods (urine dipsticks, serum tablets) only detect acetoacetate and acetone, completely missing β-OHB 1, 2
- β-OHB is the predominant ketone body in DKA 1, 2
- During treatment, β-OHB converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving 1
- Urine ketones can be falsely negative early in DKA 2
Severity Classification
Once diagnosed, stratify DKA severity based on degree of acidosis and mental status 1, 2:
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
- 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
- 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
- Mental status: Stupor/coma 1
Critical Pitfall: Euglycemic DKA
Do not dismiss DKA because glucose is <250 mg/dL. 2 Euglycemic DKA (glucose <250 mg/dL with ketoacidosis) is increasingly common, especially with SGLT2 inhibitors 1, 2. The diagnosis still requires metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L) and elevated β-OHB 1.
SGLT2 inhibitors significantly increase DKA risk and commonly cause euglycemic DKA 1, 2. Cases have even been reported with concurrent hypoglycemia (glucose <70 mg/dL) in patients on these medications 4. Other causes of euglycemic DKA include recent insulin use, decreased caloric intake, heavy alcohol consumption, chronic liver disease, and pregnancy 5, 6.
Additional Diagnostic Consideration: Diabetic Ketoalkalosis
Recent evidence shows that 23% of DKA cases present with pH >7.4 (diabetic ketoalkalosis) due to mixed acid-base disorders 7. These patients still have increased anion gap metabolic acidosis with concurrent metabolic or respiratory alkalosis 7. Importantly, 34% of these alkalemic presentations have severe ketoacidosis (β-OHB ≥3 mmol/L) and require the same treatment as traditional DKA 7.
Differential Diagnosis
Distinguish DKA from other causes of high anion gap metabolic acidosis 1:
- Alcoholic ketoacidosis (AKA): Clinical history of alcohol use, glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic 1
- Starvation ketosis: Less severe acidosis and lower ketone levels 1
- Lactic acidosis 1
- Toxic ingestions 1
Resolution Criteria
DKA is considered resolved when ALL of the following are met 1, 2: