What are the normal urine and blood beta‑hydroxybutyrate levels, and how should elevated ketones be evaluated and managed in a patient with severe hyperglycemia (hemoglobin A1c >14%)?

Normal Ketone Levels and Management in Severe Hyperglycemia

Normal Reference Values

Blood beta-hydroxybutyrate <0.5 mmol/L is considered normal, with levels 0.5-1.5 mmol/L indicating mild ketosis requiring intervention, and ≥1.5 mmol/L demanding immediate medical attention. 1

• Blood testing is strongly preferred over urine testing because urine dipsticks only detect acetoacetate and miss beta-hydroxybutyrate (the predominant ketone body), significantly underestimating total ketone concentration 1, 2, 3
• Up to 30% of first morning urine specimens show positive ketones even in healthy individuals, making urine testing unreliable for clinical decision-making 1, 2
• Ketone bodies are normally present in blood and urine but usually below detection limits of routine testing 2

Evaluation in Severe Hyperglycemia (HbA1c >14%)

Immediate Assessment Required

When blood glucose >250 mg/dL is present, immediately check blood beta-hydroxybutyrate, electrolytes, and arterial blood gas to distinguish between diabetic ketoacidosis and benign starvation ketosis. 1, 3

• DKA diagnostic criteria require ALL of the following: plasma glucose >250 mg/dL, arterial pH <7.30, serum bicarbonate <15 mEq/L, positive ketones, and anion gap >10 mEq/L 1
• Research shows that in patients with severe hyperglycemia (blood glucose ≥13.9 mmol/L), 22.4% had acute diabetic complications, with blood beta-hydroxybutyrate correlating positively with blood glucose (r=0.34, P<0.001) 4
• Serum beta-hydroxybutyrate ≥3.0 mmol/L in children and ≥3.8 mmol/L in adults can diagnose DKA in the presence of uncontrolled diabetes 5

Key Diagnostic Thresholds

Blood beta-hydroxybutyrate action thresholds:

• <0.5 mmol/L: No intervention needed 1
• 0.5-1.5 mmol/L: Initiate sick-day rules (increase fluids, monitor glucose and ketones every 3-4 hours, consider additional rapid-acting insulin) 1, 2
• ≥1.5 mmol/L: Seek immediate medical attention 1

Differential Diagnosis Considerations

Starvation ketosis presents with normal or low blood glucose, serum bicarbonate usually ≥18 mEq/L, and blood ketones 0.3-4 mmol/L, whereas DKA shows glucose >250 mg/dL with bicarbonate <15 mEq/L 1

• Research demonstrates that 73% of poorly controlled diabetics had elevated beta-hydroxybutyrate, but only 43% showed ketonuria, confirming that urine testing misses significant ketonemia 6
• When urine ketones are negative, 10% of patients still have blood beta-hydroxybutyrate ≥0.3 mmol/L; conversely, when urine ketones are positive (+ to +++), 22.62% have blood beta-hydroxybutyrate <0.3 mmol/L 4

Management Algorithm for Elevated Ketones with Severe Hyperglycemia

High-Risk Features Requiring Immediate Evaluation:

• Known type 1 diabetes 1
• History of prior DKA 1
• Currently on SGLT2 inhibitors (which can cause euglycemic DKA with glucose <250 mg/dL despite severe ketoacidosis) 1
• Presence of abdominal pain, Kussmaul respirations, or altered mental status 1

Management Steps:

For blood beta-hydroxybutyrate 0.5-1.5 mmol/L:

• Increase oral fluid intake to prevent dehydration 2
• Monitor blood glucose and ketone levels every 3-4 hours 2
• Consider additional short or rapid-acting insulin if ketone levels increase 2
• For normal blood glucose but elevated ketones, consume carbohydrates along with insulin to suppress ketone production 2

For blood beta-hydroxybutyrate ≥1.5 mmol/L or worsening symptoms:

• Immediate medical attention required 1
• Complete DKA workup including arterial blood gas, electrolytes, and anion gap 1

Critical Pitfalls to Avoid

• Never rely on urine ketone testing alone for clinical decision-making in diabetic patients with severe hyperglycemia, as it significantly underestimates ketosis 1, 2, 3
• False-positive urine ketones occur with sulfhydryl drugs like captopril 2, 3
• False-negative urine ketones occur with prolonged air exposure of test strips or highly acidic urine 2, 3
• SGLT2 inhibitors decrease the hyperglycemia typically accompanying DKA, making diagnosis more challenging and requiring lower glucose thresholds for suspicion 1
• Research shows blood beta-hydroxybutyrate testing reduces emergency department visits, hospitalization frequency, and time to recovery from DKA compared to urine testing 7