In a patient with a history of diabetes, suspected of having Diabetic Ketoacidosis (DKA), should ketones be checked in blood or urine to confirm the diagnosis?

DKA Ketone Testing: Blood β-Hydroxybutyrate is Superior to Urine Ketones

For diagnosing DKA in clinical settings, measure blood β-hydroxybutyrate (≥6.3 mmol/L) rather than relying on urine ketones, as urine testing misses the predominant ketone body in DKA and can be misleading. 1, 2, 3

Why Blood β-Hydroxybutyrate is the Gold Standard

The Critical Biochemical Problem with Urine Testing

• β-hydroxybutyrate (βOHB) is the predominant and strongest acid in DKA, comprising the majority of ketone bodies during the acute metabolic crisis 1, 2
• Standard urine dipsticks using the nitroprusside method only detect acetoacetate and acetone—they completely miss βOHB 1, 4
• This creates a dangerous gap: you're measuring the wrong ketone body when the one causing the acidosis goes undetected 1

The Metabolic Shift That Matters

• During DKA, the redox state of hepatic mitochondria shifts dramatically toward βOHB production (away from acetoacetate) due to increased NADH concentrations 1
• Assay methods that don't measure βOHB will underestimate total ketone body concentration and provide misleading clinical information 1

Specific Diagnostic Thresholds

Blood β-Hydroxybutyrate Levels

• Optimal cut-off for DKA diagnosis: ≥6.3 mmol/L 2, 3
• Normal ketone concentrations are <0.5 mmol/L 1
• The threshold of 6.3 mmol/L is substantially higher than the 0.78 mmol/L used for simple ketosis 2

Complete DKA Diagnostic Criteria

The American Diabetes Association requires all three components simultaneously 2:

• Hyperglycemia (typically >250 mg/dL, though can be lower with SGLT2 inhibitors)
• Metabolic acidosis (venous pH <7.3, serum bicarbonate <18 mEq/L, anion gap >10 mEq/L)
• Significant ketonemia (blood βOHB ≥6.3 mmol/L preferred)

When Urine Ketones Have Limited Utility

Screening and Rule-Out Only

• Urine ketones have high sensitivity with high negative predictive value—useful for ruling OUT DKA 1
• If urine ketones are negative in a patient with suspected DKA, the diagnosis is unlikely 1
• However, positive urine ketones are non-specific and require blood confirmation 1

The False Positive Problem

Positive urine ketones occur in multiple non-DKA conditions 1, 5:

• Up to 30% of first morning urine specimens in pregnant women (with or without diabetes)
• Starvation ketosis
• Post-hypoglycemia
• Alcoholic ketoacidosis (without hyperglycemia)

Critical Monitoring Pitfall to Avoid

Never Use Nitroprusside-Based Tests for Treatment Monitoring

Blood ketone determinations using the nitroprusside reaction should NOT be used to monitor DKA treatment 1, 2

Here's why this is dangerous:

• As DKA treatment succeeds and βOHB falls (the actual improvement), acetoacetate and acetone may paradoxically INCREASE 1
• Nitroprusside-based tests will show worsening ketones even as the patient clinically improves 1, 2
• This can mislead clinicians into thinking treatment is failing when it's actually working 2

Practical Clinical Algorithm

Initial Presentation with Suspected DKA

1. Order blood βOHB immediately along with venous pH, serum bicarbonate, blood glucose, and electrolytes 2, 4
2. Urine ketones can be checked simultaneously for rapid screening while awaiting blood results 1
3. If urine ketones are negative, DKA is unlikely—consider alternative diagnoses 1
4. If urine ketones are positive, do not make treatment decisions until blood βOHB results return 1, 2

During Treatment Monitoring

• Monitor blood βOHB every 2-4 hours to assess treatment response 4
• Expect ketonemia to clear more slowly than hyperglycemia 2
• DKA resolution criteria: glucose <200 mg/dL, bicarbonate ≥18 mEq/L, pH >7.3, and normalized ketones 2, 4

Special Consideration: SGLT2 Inhibitor-Associated DKA

• SGLT2 inhibitors cause euglycemic DKA where glucose may be normal or only mildly elevated 1, 2, 4
• In these cases, blood βOHB measurement becomes absolutely essential since the typical hyperglycemia clue is absent 2
• Maintain high suspicion even with borderline glucose values if metabolic acidosis and elevated βOHB are present 2

Home Monitoring for At-Risk Patients

Who Should Monitor Ketones at Home

Individuals prone to ketosis should check ketones with unexplained hyperglycemia or symptoms (abdominal pain, nausea) 1:

• Type 1 diabetes
• History of DKA
• Patients on SGLT2 inhibitors

Blood vs. Urine for Home Use

• Blood ketone testing at home reduces emergency department visits and hospitalizations by almost half compared to urine testing in children with type 1 diabetes 1
• Patients are more likely to actually perform testing when using blood meters versus urine dipsticks 1