What is the relationship between beta-hydroxybutyrate (BOH) levels and Diabetic Ketoacidosis (DKA)?

Beta-Hydroxybutyrate (BOH) and Diabetic Ketoacidosis (DKA)

Blood beta-hydroxybutyrate (BOH) is the primary and most clinically significant ketone body in DKA, serving as the most accurate diagnostic marker and monitoring parameter for DKA resolution with levels ≥3.8 mmol/L in adults being diagnostic and <1.5 mmol/L indicating resolution.

Relationship Between BOH and DKA

Pathophysiological Role

• BOH is the strongest and most prevalent ketoacid in DKA, produced during insulin deficiency when the body shifts to fat metabolism 1
• BOH represents the direct measure of the pathophysiologic derangement in DKA, unlike the nonspecific measurements of blood pH and bicarbonate 2
• During ketoacidosis, BOH accounts for approximately 75% of total ketones, making it the predominant ketone body 1

Diagnostic Value

• Blood BOH testing is superior to urine ketone testing for diagnosing and monitoring DKA 1
• BOH levels ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults are considered diagnostic for DKA in the presence of uncontrolled diabetes 1
• A BOH value of 5.3 mmol/L has been shown to predict DKA with optimal accuracy (90.6% correct classification) 2
• BOH demonstrates strong discrimination for DKA with an area under the curve of 0.95 2

Monitoring DKA Treatment

Advantages of BOH Monitoring

• Direct measurement of BOH in blood is the preferred method for monitoring DKA resolution 3
• The nitroprusside method (traditional urine ketone testing) only measures acetoacetic acid and acetone, not BOH 3
• During DKA treatment, BOH converts to acetoacetic acid, which may falsely suggest worsening ketosis if using nitroprusside methods 3

Treatment Response Assessment

• BOH normalizes earlier than ketonuria in all cases, making it a more timely indicator of treatment response 4
• BOH correlates well with bicarbonate (r=-0.24139; P=0.0161) and pH (r=-0.56419; P<0.0001) 4
• As many as 10% of patients may still have ketonuria when blood ketone levels have already normalized (<0.5 mmol/L) 4

Resolution Criteria

BOH as Resolution Marker

• A BOH value of <1.5 mmol/L can be used to define resolution of DKA, with a sensitivity of 83% and specificity of 87% 5
• Traditional DKA resolution criteria include:
  • Glucose <200 mg/dL
  • Serum bicarbonate ≥18 mEq/L
  • Venous pH ≥7.3 3, 1

Clinical Application

• BOH measurement is an easy, practical, and reliable monitoring method in DKA and may be used to adjust insulin treatment 4
• Home monitoring supplies for BOH should be provided to patients at risk for DKA, including those with type 1 diabetes, history of DKA, and patients treated with SGLT2 inhibitors 1

Special Considerations

SGLT2 Inhibitor Users

• SGLT2 inhibitor users should measure BOH at any sign of illness regardless of glucose levels due to risk of euglycemic ketoacidosis 1
• Each 0.1 mmol/L increase in baseline BOH increases DKA risk by 18% 1

Monitoring Recommendations

• Regular BOH monitoring is recommended for high-risk individuals, including those with type 1 diabetes, pregnant women, and patients taking SGLT2 inhibitors 1
• Consider continuous ketone monitoring for high-risk patients, especially those with type 1 diabetes, pregnancy, on SGLT2 inhibitors, with recurrent DKA, or on low carbohydrate diets 1

By understanding the central role of BOH in DKA, clinicians can more accurately diagnose, monitor, and determine resolution of this potentially life-threatening condition.