D-lactate: a novel contributor to metabolic acidosis and high anion gap in diabetic ketoacidosis.

Diabetic ketoacidosis (DKA),the most common and serious acute complication of diabetes, is characterized by hyperglycemia and severe high–anion-gap metabolic ac-idosis with ketonemia (1). In DKA, the high anion gap is attributed largely to excessive production of blood ketone bodies, and serum ␤-hydroxybutyrate quantification is recommended for the diagnosis and monitoring of DKA (2). However, even counting of all the ketone bodies , including ␤-hydroxybutyrate, does not account for the entire anion gap, suggesting that there are additional sources of anion production in DKA. We recently demonstrated that plasma D-lactate concentrations were greatly increased in DKA compared with the concentrations in diabetic patients or a healthy control group (3). Nevertheless, the clinical value of D-lactate measurement in metabolic acidosis, especially the contribution of D-lactate to the metabolic acidosis and high anion gap in DKA, is not well appreciated. We report here that decreasing D-lactate concentrations are associated with improved clinical situations, whereas increased lac-tate concentrations are associated with the severity of metabolic aci-dosis and high anion gap in patients with DKA. The study included 38 diabetic patients with DKA, 42 diabetic patients without DKA, and 40 healthy controls. The institutional ethics review board of the First Affiliated Hospital of Wenzhou Medical College approved the study, and written informed consent was obtained from all study participants. For patients with DKA, blood samples were collected at the time of admission to the emergency room and following medical treatment after admission, when the patient's condition became stabilized. Plasma methylglyoxal was assayed by LC-MS (3). Plasma D-lactate concentration was determined by an enzymatic assay kit (BioVision Corporation). Other biochemical analyses were performed on automated chemistry analyzers. Concentrations of plasma glucose [mean (SD) 450.45 (201.80) mg/dL], ␤-hydroxybutyrate [58.41 (37.38) mg/dL], and methylglyoxal [75.72 (46.25) ng/mL] were greatly increased compared with the concentrations in diabetic patients without DKA and healthy controls (all P Ͻ 0.001). Interestingly, plasma D-lactate concentrations were markedly increased in diabetic patients with DKA [3.44 (1.99) mmol/L] compared to diabetic patients without DKA [0.48 (0.56) mmol/L] and healthy controls [0.32 (0.30) mmol/L] (P Ͻ 0.001). Increased D-lactate concentrations were greatly reduced following treatment [3.44 (1.99) vs 0.53 (0.35) mmol/L, P Ͻ 0.001]. The reduction of D-lactate concentration was consistent with the changes in and improvement of plasma glucose mmol/L] following treatment (all P Ͻ 0.001). Plasma L-lactate concentrations were also increased in DKA, but to a lesser degree compared to D-lactate concentrations Fig. 1. …