Do Patients Have High Anion Gaps in Diabetic Ketoacidosis?
Yes, diabetic ketoacidosis (DKA) characteristically presents with a high anion gap metabolic acidosis, with anion gap values typically >10 mEq/L and often exceeding 12 mEq/L in moderate to severe cases. 1
Diagnostic Criteria for Anion Gap in DKA
The American Diabetes Association establishes that DKA is diagnosed by the presence of hyperglycemia (blood glucose >250 mg/dL), ketosis, and metabolic acidosis with an elevated anion gap >10 mEq/L. 1 The severity classification further specifies:
- Mild DKA: Anion gap >10 mEq/L with bicarbonate 15-18 mEq/L 1
- Moderate DKA: Anion gap >12 mEq/L with bicarbonate 10-15 mEq/L 1
- Severe DKA: Anion gap >12 mEq/L with bicarbonate <10 mEq/L 1
Pathophysiology of the High Anion Gap
The elevated anion gap in DKA results from accumulation of unmeasured anions, primarily ketoacids (beta-hydroxybutyrate and acetoacetate). 2 Recent evidence demonstrates that D-lactate also contributes significantly to the anion gap, with plasma D-lactate levels markedly elevated in DKA (3.82±2.50 mmol/L) compared to diabetic controls (0.47±0.55 mmol/L), and D-lactate correlates strongly with both acidosis and anion gap (r=0.686). 3
Important Clinical Nuances
Mixed Acid-Base Disorders Can Mask the High Anion Gap
A critical pitfall: Not all DKA patients present with acidemia despite having a high anion gap. Recent data shows that 23.3% of DKA cases present with pH >7.4 (diabetic ketoalkalosis), yet all of these cases still had an increased anion gap metabolic acidosis (anion gap ≥16 mmol/L), with 34% having severe ketoacidosis. 4 This occurs when concurrent metabolic alkalosis (47.2% of cases) or respiratory alkalosis (81.1% of cases) masks the underlying high anion gap acidosis. 4
Hyperchloremic Acidosis Can Develop During Treatment
During DKA treatment with intravenous saline, hyperchloremic metabolic acidosis develops in 69.3% of patients (mean onset 6.3 hours), which causes the anion gap to normalize despite persistent acidosis. 5 At 12 hours of treatment, the hyperchloremia group exhibited a low anion gap (mean 12.8 mEq/L) even though acidosis continued based on pH and bicarbonate. 5 Monitor anion gap, blood ketones, and Cl⁻/Na⁺ ratio to differentiate ongoing DKA from treatment-induced hyperchloremic acidosis and avoid unnecessarily prolonged IV therapy. 5
Differential Diagnosis Considerations
DKA must be distinguished from other high anion gap metabolic acidoses, including:
- Lactic acidosis 2
- Toxic ingestions (salicylate, methanol, ethylene glycol, paraldehyde) 2
- Uremic acidosis (though chronic renal failure more typically presents with hyperchloremic rather than high anion gap acidosis) 2
- Starvation ketosis: Serum bicarbonate usually not lower than 18 mEq/L, distinguishing it from DKA 2
- Alcoholic ketoacidosis: Glucose typically <250 mg/dL or even hypoglycemic, unlike DKA's characteristic hyperglycemia >250 mg/dL 6
Clinical Application
When evaluating a patient with suspected DKA, calculate the anion gap using Na⁺ + K⁺ - Cl⁻ - HCO₃⁻ and obtain arterial blood gases to confirm metabolic acidosis. 7 The presence of an elevated anion gap (>10 mEq/L) combined with hyperglycemia >250 mg/dL and positive ketones confirms DKA. 1 However, do not exclude DKA based on normal or alkalemic pH alone—check the anion gap and ketone levels, as mixed acid-base disorders are common. 4