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Objective: Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO(3)] and pH) and qualitative nature (the presence of ketonemia/ketonuria). The present study was undertaken to determine whether quantitative measurement of a ketone body anion could be used to diagnose DKA., Research Design and Methods: A retrospective review of records from hospitalized diabetic patients was undertaken to determine the concentration of serum beta-hydroxybutyrate (betaOHB) that corresponds to a HCO(3) level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission betaOHB and HCO(3) values were recorded from 466 encounters, 129 in children and 337 in adults., Results: A HCO(3) level of 18 mEq/l corresponded with betaOHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold betaOHB values to define DKA, there was substantial discordance (approximately > or = 20%) between betaOHB and conventional diagnostic criteria using HCO(3), pH, and glucose. In patients with DKA, there was no correlation between HCO(3) and glucose levels on admission and a significant but weak correlation between betaOHB and glucose levels (P < 0.001)., Conclusions: Where available, serum betaOHB levels > or = 3.0 and > or = 3.8 mmol/l in children and adults, respectively, in the presence of uncontrolled diabetes can be used to diagnose DKA and may be superior to the serum HCO(3) level for that purpose. The marked variability in the relationship between betaOHB and HCO(3) is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis.