How is diabetic ketoacidosis (DKA) diagnosed using beta-hydroxybutyric acid (BHB) levels?

Diagnosing Diabetic Ketoacidosis Using Beta-Hydroxybutyric Acid

Specific measurement of beta-hydroxybutyrate (βOHB) in blood should be used for diagnosis of diabetic ketoacidosis (DKA) with a threshold value of ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults, when combined with hyperglycemia and metabolic acidosis. 1, 2

Diagnostic Criteria for DKA Using βOHB

DKA diagnosis requires the presence of three key elements:

1. Hyperglycemia (blood glucose >250 mg/dL)
2. Metabolic acidosis (increased anion gap, pH <7.3, bicarbonate <15-18 mEq/L)
3. Ketosis (elevated blood ketone bodies)

Why βOHB is Superior for DKA Diagnosis

• βOHB is the predominant ketone body in DKA, accounting for approximately 75% of total ketones 1
• Direct βOHB measurement provides more accurate assessment of ketosis severity than traditional nitroprusside-based methods 1
• βOHB levels correlate strongly with anion gap (r = 0.66) and inversely with bicarbonate (r = -0.69) 3

Diagnostic Thresholds

• Adults: βOHB ≥3.8 mmol/L corresponds to bicarbonate level of 18 mEq/L (traditional DKA threshold) 2
• Children: βOHB ≥3.0 mmol/L corresponds to bicarbonate level of 18 mEq/L 2
• Screening threshold: βOHB ≥0.66 mmol/L has 95% sensitivity and 89.2% specificity for DKA 4
• Diagnostic threshold: βOHB ≥1.0 mmol/L has 85.1% sensitivity and 95.3% specificity for DKA 4

Advantages of βOHB Testing Over Traditional Methods

1. More accurate reflection of ketosis:

   • Nitroprusside-based methods (urine dipsticks/tablets) only detect acetoacetate and acetone, not βOHB 1, 5
   • During DKA, the βOHB:acetoacetate ratio shifts from the normal 1:1 to as high as 10:1 1

2. Earlier detection and monitoring:

   • Point-of-care βOHB testing at triage has 98% sensitivity and 85% specificity for DKA 3
   • βOHB normalizes earlier than ketonuria in all cases (15.5-37.3 hours vs. 18.8-41.7 hours) 6

3. Better for treatment monitoring:

   • During successful DKA treatment, βOHB converts to acetoacetate, which can falsely suggest worsening ketosis if using nitroprusside methods 1
   • Resolution of acidosis or reduction in blood βOHB is the preferred marker for successful DKA treatment 1

Practical Implementation

Specimen Collection and Handling

• Blood samples can be collected into heparin, EDTA, fluoride, citrate, or oxalate tubes 1
• Whole blood specimens are stable at 4°C for up to 24 hours 1
• Serum/plasma specimens are stable for up to 1 week at room temperature, 2 weeks at 4°C 1

Common Pitfalls to Avoid

1. Relying solely on urine ketone testing:

   • Urine ketone tests miss βOHB, potentially underestimating ketosis severity 1, 5
   • False-positive results can occur with highly colored urine 1, 5
   • Up to 30% of first morning urine specimens from pregnant women may show positive ketones without pathology 1

2. Using nitroprusside-based blood ketone tests to monitor DKA treatment:

   • As βOHB converts to acetoacetate during treatment, nitroprusside tests may show falsely worsening ketosis 1

3. Overlooking euglycemic DKA:

   • SGLT2 inhibitors can cause DKA with less pronounced hyperglycemia 1, 5
   • Always check βOHB in patients on SGLT2 inhibitors with symptoms of ketosis, even without marked hyperglycemia 1

Special Considerations

• SGLT2 inhibitor users: These patients should measure ketones (preferably blood βOHB) at any sign of illness, regardless of glucose levels 1
• Pregnant women: May have physiologic ketonuria, especially in morning specimens 1
• Alcoholic ketoacidosis: Will have positive ketone readings but typically without hyperglycemia 1

By directly measuring βOHB, clinicians can more accurately diagnose DKA, initiate appropriate treatment earlier, and better monitor treatment response compared to traditional nitroprusside-based ketone testing methods.