From the Guidelines
The anion gap is typically high in diabetic ketoacidosis (DKA). In DKA, the body produces excessive amounts of ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) due to insulin deficiency and increased counter-regulatory hormones. These ketone bodies are acidic and release hydrogen ions, causing metabolic acidosis. Since these ketoacids contribute unmeasured anions to the blood, they increase the anion gap, which is the difference between measured cations (primarily sodium) and measured anions (chloride and bicarbonate). Normal anion gap is typically 8-12 mEq/L, but in DKA it often exceeds 20 mEq/L, as seen in the diagnostic criteria for DKA, which includes an anion gap of >10 1. The severity of the anion gap elevation generally correlates with the severity of ketoacidosis.
When treating DKA, monitoring the anion gap helps assess response to therapy, as it should gradually normalize with appropriate insulin administration and fluid resuscitation, as recommended in the management protocol for DKA 1. The high anion gap metabolic acidosis in DKA is accompanied by other laboratory abnormalities including hyperglycemia, ketonemia, and often electrolyte disturbances such as hypokalemia (after treatment begins) and hypophosphatemia. It's also important to note that the anion gap can be used to monitor resolution of acidosis, along with venous pH, as repeat arterial blood gases are generally unnecessary 1.
Some key points to consider in the management of DKA include:
- Monitoring anion gap and venous pH to assess response to therapy
- Using the nitroprusside method to measure ketone levels, while keeping in mind that it only measures acetoacetic acid and acetone, and not beta-hydroxybutyrate 1
- Adjusting insulin administration and fluid replacement to maintain adequate plasma insulin levels and normalize anion gap and venous pH
- Considering the use of regular insulin given subcutaneously or intramuscularly every hour for mild DKA, as it is as effective as intravenous administration in lowering blood glucose and ketone bodies 1
From the Research
Anion Gap in Diabetic Ketoacidosis (DKA)
- The anion gap is typically high in diabetic ketoacidosis (DKA) 2, 3, 4, 5.
- A high anion gap in DKA suggests that some unmeasured anions must contribute to the generation of the anion gap 4.
- Studies have shown that plasma D-lactate levels are highly elevated and associated with metabolic acidosis and the high anion gap in DKA 4.
- The anion gap is calculated as the difference between the sum of sodium and potassium ions and the sum of chloride and bicarbonate ions, and a high anion gap indicates the presence of unmeasured anions 5.
- In DKA, the anion gap is often increased due to the accumulation of ketones and other unmeasured anions 2, 3.
- However, it's worth noting that there can be cases where DKA presents with a normal or low anion gap, especially in cases of euglycemic DKA or when there are concurrent acid-base disorders 3, 6.