Will ketone bodies be present in serum and should they be tested?

Ketone Bodies in Serum: Testing Recommendations

Yes, ketone bodies are present in serum and should be tested, with specific measurement of β-hydroxybutyrate (bOHB) being the preferred method for diagnosis and monitoring of diabetic ketoacidosis. 1

Presence of Ketone Bodies in Serum

Ketone bodies are definitely present in serum, with three primary types:

• β-hydroxybutyrate (bOHB) - the predominant ketone body in diabetic ketoacidosis
• Acetoacetate (AcAc)
• Acetone (present in smaller quantities)

Under normal conditions, bOHB and AcAc are present in approximately equimolar amounts (1:1 ratio). However, in conditions like diabetic ketoacidosis (DKA), the ratio shifts significantly toward bOHB, which can rise to as high as 10:1 2.

Testing Recommendations

When to Test Serum Ketones

Serum ketone testing is indicated in:

• Patients with suspected DKA
• Diabetic patients with symptoms of illness
• Deteriorating glycemic control
• Patients on SGLT2 inhibitors (who have increased risk of DKA)
• Ketosis-prone individuals during illness

Preferred Testing Method

The 2023 Diabetes Care guidelines strongly recommend:

• Specific measurement of β-hydroxybutyrate (bOHB) in blood for diagnosis of DKA and monitoring during treatment 1
• Blood ketone determinations that rely on the nitroprusside reaction should not be used to monitor treatment of DKA 1

Testing Cutoffs

For diagnosis of DKA, research suggests optimal cut-off values of:

• 6.3 mmol/l of β-hydroxybutyrate
• 1.4 mmol/l of acetoacetate
• 8.0 mmol/l of total ketone body 3

Why bOHB Measurement is Superior

1. Most abundant ketone in DKA: bOHB is the predominant ketone body in DKA, often accounting for 75% or more of total ketones 1

2. Nitroprusside limitations: The traditional nitroprusside method (used in many dipsticks and tablets) only measures acetoacetate and sometimes acetone, but not bOHB 1

3. Misleading results during treatment: During DKA treatment, bOHB is converted to acetoacetate, which can make nitroprusside-based tests falsely suggest worsening ketosis when the patient is actually improving 1

4. Quantitative assessment: Newer bOHB tests provide quantitative results rather than the semiquantitative results of nitroprusside tests 2

Specimen Collection and Stability

For bOHB testing:

• Blood samples can be collected into heparin, EDTA, fluoride, citrate, or oxalate
• Whole blood specimens are stable at 4°C for up to 24 hours
• Serum/plasma specimens are stable for up to 1 week at room temperature, 2 weeks at 4°C, and several weeks at -20°C 1

Pitfalls to Avoid

1. Relying solely on urine ketone testing: While urine ketones have high sensitivity for DKA, they don't measure bOHB and can't be used to monitor treatment progress 1

2. Using nitroprusside-based blood tests for monitoring: These tests may show falsely worsening results during successful treatment as bOHB converts to acetoacetate 1

3. Ignoring ketone testing in type 2 diabetes: Although DKA is most commonly associated with type 1 diabetes, it can occur in type 2 diabetes, especially in patients taking SGLT2 inhibitors 1

4. Missing non-hyperglycemic DKA: Patients on SGLT2 inhibitors may develop DKA without significant hyperglycemia, making ketone testing particularly important 1

In summary, serum ketone bodies are present and should be tested using specific bOHB measurement methods rather than traditional nitroprusside-based tests for accurate diagnosis and monitoring of diabetic ketoacidosis.