Can BHB Levels Distinguish Between Starvation, Diabetic, and Alcoholic Ketosis?
Yes, monitoring beta-hydroxybutyrate (BHB) levels combined with plasma glucose measurements can effectively distinguish between these three forms of ketoacidosis, with glucose being the critical differentiating factor. 1
Diagnostic Algorithm Using BHB and Glucose
Step 1: Measure BHB and Plasma Glucose Simultaneously
BHB measurement is the preferred method for diagnosing and monitoring all forms of ketoacidosis because nitroprusside-based tests (urine dipsticks) fail to detect BHB, which is the predominant ketone body in ketoacidosis. 2, 1
Step 2: Interpret BHB Levels
The following interpretative ranges apply to blood BHB concentrations:
All cases with significant BHB (>250 mg/L) will also have acetone present (>2 mg/dL), so acetone can serve as an initial screening marker to determine when BHB measurement is necessary. 4
Step 3: Use Glucose to Differentiate the Etiology
The plasma glucose concentration is the key distinguishing feature:
Diabetic Ketoacidosis (DKA)
- Plasma glucose >250 mg/dL 2, 1
- BHB typically >250 mg/L 1
- pH <7.3 and bicarbonate <18 mEq/L 1
- Vitreous humor glucose >6.9 mmol/L indicates hyperglycemia prior to death 4
Alcoholic Ketoacidosis (AKA)
- Glucose normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic 2, 1
- BHB can be significantly elevated (5.2-22.5 mmol/L in severe cases) 5
- Clinical history of alcohol abuse with recent cessation 2, 1
- Most patients do not have ethanol detected in blood at presentation 6
Starvation Ketosis
- Glucose normal to mildly elevated (rarely >250 mg/dL) 2, 7
- Serum bicarbonate usually not lower than 18 mEq/L (less severe acidosis than DKA or AKA) 2, 7
- BHB levels typically mild compared to DKA or AKA 8
- Clinical history of prolonged fasting or malnutrition 7, 8
Critical Pitfalls to Avoid
Do Not Use Nitroprusside Methods for Monitoring
Nitroprusside-based tests (urine dipsticks, serum tablets) should never be used to monitor treatment of ketoacidosis. 2, 1 During treatment, BHB converts to acetoacetate, making these tests falsely suggest worsening ketosis when the patient is actually improving. 1
Recognize That Ethanol May Be Present in AKA
Contrary to older beliefs, ethanol is not always low (<10 mg/dL) or absent in cases of AKA. 3 Many patients with alcoholic ketoacidosis have stopped drinking days before presentation, explaining the absence of ethanol. 5, 6
Consider Lactic Acidosis in Active Drinkers
Patients who continued drinking until shortly before admission may have predominant lactic acidosis with only minor BHB elevations, rather than true alcoholic ketoacidosis. 5, 6
Additional Distinguishing Features
Acidosis Severity
- DKA: pH can be <7.0 in severe cases 1
- AKA: Severe acidemia is uncommon; some patients may even be alkalemic due to coexisting respiratory or metabolic alkalosis 5
- Starvation ketosis: Bicarbonate usually ≥18 mEq/L 2, 7
Clinical Context
The clinical history remains essential: DKA occurs in diabetics (type 1 or type 2 on SGLT2 inhibitors), AKA in chronic alcohol abusers with recent decreased intake and poor nutrition, and starvation ketosis in prolonged fasting or malnutrition. 2, 1
Vitreous Humor Glucose (Post-Mortem Cases)
In forensic settings, vitreous humor glucose >6.9 mmol/L distinguishes DKA from other causes of ketoacidosis. 4