Closing the anion gap: contribution of D-lactate to diabetic ketoacidosis

Clin Chim Acta. 2011 Jan 30;412(3-4):286-91. doi: 10.1016/j.cca.2010.10.020. Epub 2010 Oct 29.


Background: A high anion gap in diabetic ketoacidosis (DKA) suggests that some unmeasured anions must contribute to the generation of the anion gap. We investigated the contribution of D-lactate to the anion gap in DKA.

Methods: Diabetic patients with and without DKA and high anion gap were recruited. Plasma D-lactate was quantified by HPLC. Plasma methylglyoxal was assayed by liquid chromatography-tandem mass spectrometry.

Results: The plasma fasting glucose, β-hydroxybutyrate, and blood HbA1c levels were highly elevated in DKA. Plasma anion gap was significantly increased in DKA (20.59±6.37) compared to either the diabetic (7.50±1.88) or the control group (6.53±1.75) (p<0.001, respectively). Moreover, plasma D-lactate levels were markedly increased in DKA (3.82±2.50 mmol/l) compared to the diabetic (0.47±0.55 mmol/l) or the control group (0.25±0.35 mmol/l) (p<0.001, respectively). Regression analysis demonstrated that D-lactate was associated with acidosis and anion gap (r=0.686, p<0.001).

Conclusions: Plasma D-lactate levels are highly elevated and associated with metabolic acidosis and the high anion gap in DKA. Laboratory monitoring of d-lactate will provide valuable information for assessment of patients with DKA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Bicarbonates / blood
  • Blood Glucose / metabolism
  • Diabetic Ketoacidosis / blood*
  • Female
  • Humans
  • Lactic Acid / blood*
  • Male
  • Middle Aged
  • Pyruvaldehyde / blood


  • Bicarbonates
  • Blood Glucose
  • Lactic Acid
  • Pyruvaldehyde
  • 3-Hydroxybutyric Acid