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Can Serum β-Hydroxybutyrate Be Used to Diagnose Diabetic Ketoacidosis?

¹ Division of Endocrinology, Diabetes, Nutrition, and Metabolism, Mayo Clinic, Rochester, Minnesota
² Division of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota
³ Division of Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota
⁴ Division of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
⁵ Mayo Clinic, Jacksonville, Florida

Address correspondence and reprint requests to John M. Miles, MD, Endocrine Research Unit, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail: miles.john{at}mayo.edu

OBJECTIVE—Current criteria for the diagnosis of diabetic ketoacidosis (DKA) are limited by their nonspecificity (serum bicarbonate [HCO₃] 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 β-hydroxybutyrate (βOHB) that corresponds to a HCO₃ level of 18 mEq/l, the threshold value for diagnosis in recently published consensus criteria. Simultaneous admission βOHB and HCO₃ values were recorded from 466 encounters, 129 in children and 337 in adults.

RESULTS—A HCO₃ level of 18 mEq/l corresponded with βOHB levels of 3.0 and 3.8 mmol/l in children and adults, respectively. With the use of these threshold βOHB values to define DKA, there was substantial discordance (20%) between βOHB and conventional diagnostic criteria using HCO₃, pH, and glucose. In patients with DKA, there was no correlation between HCO₃ and glucose levels on admission and a significant but weak correlation between βOHB and glucose levels (P < 0.001).

CONCLUSIONS—Where available, serum βOHB levels 3.0 and 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 HCO₃ level for that purpose. The marked variability in the relationship between βOHB and HCO₃ is probably due to the presence of other acid-base disturbances, especially hyperchloremic, nonanion gap acidosis.

Abbreviations: AcAc, acetoacetate • βOHB, β-hydroxybutyrate • DKA, diabetic ketoacidosis • HCO₃, bicarbonate • HHS, hyperglycemic hyperosmolar syndrome • POC, point-of-care • ROC, receiver operating characteristic

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