What are the clinical uses of Beta-hydroxybutyrate (BHB)?

Clinical Uses of Beta-Hydroxybutyrate (BHB)

Beta-hydroxybutyrate (BHB) is primarily used clinically for the diagnosis and monitoring of diabetic ketoacidosis (DKA), with specific blood BHB measurement being superior to urine ketone testing for both diagnosis and treatment monitoring of DKA. 1

Primary Clinical Applications

1. Diagnosis and Monitoring of Diabetic Ketoacidosis (DKA)

• Diagnostic Use:

  • BHB is the predominant ketone body in DKA and specific measurement in blood is recommended for accurate diagnosis 1
  • Blood BHB measurement is preferred over urine ketone testing as it provides more accurate assessment of ketosis severity 2
  • Diagnostic criteria for DKA includes elevated blood ketones/BHB along with hyperglycemia and acidosis with increased anion gap 1

• Monitoring During Treatment:

  • BHB should be used for monitoring during DKA treatment rather than nitroprusside-based methods 1
  • Resolution of acidosis or reduction in blood BHB is the marker for successful treatment of DKA 1
  • Blood ketone determinations that rely on the nitroprusside reaction should NOT be used to monitor treatment of DKA as they don't measure BHB specifically 1

2. Monitoring High-Risk Individuals for Ketosis

• Recommended for:

  • People with type 1 diabetes 1
  • Individuals with history of DKA 1
  • Patients treated with SGLT2 inhibitors 1
  • Pregnant women with diabetes 2

• When to Monitor:

  • During unexplained hyperglycemia 1
  • When experiencing symptoms of ketosis (abdominal pain, nausea) 1
  • During acute illness or stress 2
  • For SGLT2 inhibitor users: at any sign of illness, regardless of glucose levels 2

Mechanism of Action and Physiological Roles

BHB serves multiple functions beyond being a metabolite:

1. Energy substrate: Provides an efficient alternative fuel source for the brain, heart, and skeletal muscles during fasting or ketosis 3, 4

2. Signaling molecule:

   • Acts as an endogenous inhibitor of histone deacetylases (HDACs) 5
   • Serves as a ligand for cell surface receptors 5
   • Upregulates genes involved in protection against oxidative stress 3

3. Mitochondrial effects:

   • Alters NAD+/NADH and Q/QH2 couples 3
   • Reduces production of mitochondrial reactive oxygen species 3
   • Enhances mitochondrial respiration through Ca²⁺-dependent mechanisms 6

4. Anti-inflammatory properties:

   • Interacts with inflammasomes in immune cells 3
   • Reduces production of inflammatory cytokines 3

Practical Clinical Applications

For Diabetes Management:

1. Home monitoring for high-risk patients:

   • Provide home monitoring supplies for BHB to patients at risk for DKA 1
   • Instruct patients to check BHB during illness, stress, or unexplained hyperglycemia 1
   • Implement sick day rules if ketones are elevated 2

2. SGLT2 inhibitor users:

   • Assess underlying susceptibility to ketosis before prescribing 1
   • Provide education on risks, symptoms, and prevention strategies 1
   • Prescribe home monitoring supplies for BHB 1
   • Reassess susceptibility and education throughout treatment 1

For Emergency/Hospital Settings:

1. DKA diagnosis protocol:

   • Measure blood BHB specifically rather than relying on urine ketones 1
   • Combine with assessment of plasma glucose, arterial blood gases, and anion gap calculation 2
   • Use anion gap ≥12 mEq/L as a reliable alternative marker 2

2. DKA treatment monitoring:

   • Use serial BHB measurements to assess treatment efficacy 1
   • Do NOT use nitroprusside-based ketone tests for treatment monitoring 1

Emerging Research Applications

While not yet standard clinical practice, research suggests potential therapeutic applications:

1. Neurological conditions:

   • Neurodegenerative disorders 4
   • Epilepsy 7, 6
   • Migraine 7

2. Metabolic and cardiovascular conditions:

   • Heart failure 7
   • Diabetes management beyond DKA 7, 4

3. Other conditions:

   • Sepsis-related muscle atrophy 7
   • Inflammatory conditions 3, 4

Common Pitfalls and Caveats

1. Measurement limitations:

   • Urine ketone tests using nitroprusside reaction do not detect BHB 1
   • Blood ketone determinations using nitroprusside reaction should not be used for monitoring DKA treatment 1

2. Physiological ketosis vs. pathological states:

   • Positive urine ketone readings can occur in up to 30% of first morning specimens from pregnant women 1
   • Ketosis can occur during starvation, after hypoglycemia, and in alcoholic ketoacidosis 1

3. SGLT2 inhibitor-associated ketosis:

   • Can present as euglycemic ketoacidosis (normal glucose levels) 1
   • Requires specific monitoring of BHB regardless of glucose levels 2

4. Specimen considerations:

   • For specific BHB determinations, specimen requirements differ among methods 1
   • Whole blood specimens are generally stable at 4°C for up to 24h 1
   • Serum/plasma specimens are stable for up to 1 week at room temperature 1

By understanding these clinical applications and monitoring protocols, healthcare providers can effectively utilize BHB measurement to improve patient outcomes, particularly in the management of diabetic ketoacidosis and prevention of metabolic emergencies.