How is beta-hydroxybutyrate (BHB) level managed?

Management of Beta-Hydroxybutyrate (BHB) Levels

Beta-hydroxybutyrate (BHB) levels should be directly measured rather than using nitroprusside-based tests for diagnosis and monitoring of diabetic ketoacidosis, with levels ≥1.5 mmol/L indicating significant ketosis requiring immediate intervention. 1, 2

Interpretation of BHB Levels

• BHB levels <0.6 mmol/L are considered normal range 2
• BHB levels between 0.6-1.5 mmol/L indicate mild to moderate ketosis, requiring monitoring and possible intervention 2
• BHB levels >1.5 mmol/L, when accompanied by hyperglycemia and acidosis, are diagnostic of diabetic ketoacidosis (DKA) 2
• Caution is needed even with BHB levels ≥0.6 mmol/L in patients with diabetes, as this may indicate early ketosis 2

Clinical Management Based on BHB Levels

For Patients with Diabetes:

• Monitoring recommendations:

  • Measure BHB when blood glucose is persistently elevated (>250 mg/dL) 2
  • Check BHB during illness or when symptoms of ketosis appear 2
  • For patients on SGLT2 inhibitors, regular monitoring is essential due to increased risk of euglycemic DKA 2, 3

• Physical activity considerations:

  • Postpone intense physical activity when BHB ≥1.5 mmol/L due to risk of worsening ketosis 1, 2
  • Exercise caution with moderate activity when BHB levels are ≥0.6 mmol/L 1, 2

• For confirmed DKA (BHB >1.5 mmol/L with hyperglycemia and acidosis):

  • Initiate insulin therapy and fluid resuscitation according to DKA protocols 1, 2
  • Monitor BHB levels during treatment rather than using urine ketone tests 1, 4
  • Continue treatment until BHB levels decrease to <0.6 mmol/L 2

Special Populations:

• Children with glycogen storage disease type I:

  • Monitor BHB levels as they may be mildly or moderately increased relative to free fatty acid levels 1
  • Ensure adequate metabolic control to prevent complications 1

• Patients on SGLT2 inhibitors:

  • Increased vigilance is required as DKA risk increases by 8% with each 0.1-mmol/L increase from baseline BHB 3
  • Monitor BHB levels regularly, especially during illness, regardless of blood glucose levels 2, 3

Testing Methods

• Preferred method: Direct measurement of blood BHB using specific enzymatic assays 1, 2
• Not recommended: Blood or urine ketone determinations that rely on the nitroprusside reaction, as these do not quantify BHB specifically 1
• Point-of-care testing: Bedside monitoring of blood BHB levels using devices like Precision Xtra meter shows good correlation with laboratory methods and can simplify management 4

Pitfalls and Caveats

• Urine ketone tests detect acetoacetate but not BHB, which is the predominant ketone body in DKA, leading to potential false negatives during treatment 1, 5
• BHB levels may be elevated in other conditions besides DKA, including alcoholic ketoacidosis, starvation, and pregnancy 1
• Some drugs like GHB (gamma-hydroxybutyrate) can be confused with BHB but have different clinical implications 1
• Recent research has identified a previously unknown BHB metabolic pathway that generates BHB-amino acids with potential anti-obesity effects, suggesting broader metabolic roles for BHB beyond energy metabolism 6
• In patients with endogenous hyperinsulinemic hypoglycemia, elevated BHB levels (>2700 μmol/L) can still occur, particularly after partial pancreatectomy, and should not rule out recurrence of the condition 7