Diagnosing Diabetic Ketoacidosis Without Beta-Hydroxybutyrate Testing
When beta-hydroxybutyrate testing is unavailable, DKA should be diagnosed using a combination of plasma glucose, serum ketones, arterial blood gases, anion gap calculation, and urinary ketones, with an anion gap ≥12 mEq/L being the most reliable alternative marker. 1
Diagnostic Algorithm for DKA Without Beta-Hydroxybutyrate
Initial Laboratory Evaluation:
- Plasma glucose (>250 mg/dL)
- Arterial blood gases (pH <7.30)
- Serum bicarbonate (<18 mEq/L)
- Calculated anion gap (>10-12 mEq/L)
- Urine ketones by dipstick (positive)
- Serum ketones by nitroprusside reaction (positive)
Anion Gap Calculation:
- Formula: [Na⁺] - ([Cl⁻] + [HCO₃⁻])
- DKA typically presents with anion gap >12 mEq/L
- Higher anion gaps (>12) correlate with more severe ketoacidosis 1
Severity Assessment:
- Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L
- Moderate DKA: pH 7.00-7.24, bicarbonate 10-<15 mEq/L
- Severe DKA: pH <7.00, bicarbonate <10 mEq/L 1
Limitations of Traditional Ketone Testing
- Nitroprusside-based methods (urine dipsticks/tablets) only detect acetoacetate and acetone, not beta-hydroxybutyrate 2
- During DKA, the beta-hydroxybutyrate:acetoacetate ratio shifts from 1:1 to as high as 10:1, meaning urine ketones may underestimate total ketosis 2
- During treatment, beta-hydroxybutyrate converts to acetoacetate, which can falsely suggest worsening ketosis if using nitroprusside methods 2
Clinical Presentation Considerations
- Classic symptoms include polyuria, polydipsia, polyphagia, weight loss, vomiting, abdominal pain, dehydration, weakness, and altered mental status 1
- Physical findings may include poor skin turgor, Kussmaul respirations, tachycardia, and hypotension 1
- Up to 25% of DKA patients have emesis, which may be coffee-ground in appearance 1
- Patients may be normothermic or hypothermic despite infection due to peripheral vasodilation 1
Differential Diagnosis
- Starvation ketosis: Mildly elevated glucose (rarely >250 mg/dL), bicarbonate usually not <18 mEq/L
- Alcoholic ketoacidosis: Positive ketones but typically without hyperglycemia
- Other high anion gap acidoses: Lactic acidosis, salicylate/methanol/ethylene glycol ingestion, chronic renal failure 1
Pitfalls to Avoid
- Don't rely solely on urine ketones: They may be falsely negative or underestimate ketosis severity
- Don't dismiss DKA in patients with only mildly elevated glucose: Some patients, especially those taking SGLT2 inhibitors, can develop euglycemic DKA 2
- Don't forget to calculate the anion gap: This is crucial when beta-hydroxybutyrate testing is unavailable
- Don't wait for all classic symptoms: DKA can present atypically, especially in elderly patients
- Don't delay treatment while waiting for complete laboratory results: If clinical suspicion is high, begin treatment
Management Considerations
- Initial fluid therapy with isotonic saline (0.9% NaCl) at 15-20 ml/kg/h during the first hour
- Insulin therapy after initial fluid resuscitation
- Frequent monitoring of glucose, electrolytes, and acid-base status
- Identification and treatment of precipitating factors 1
By following this diagnostic approach when beta-hydroxybutyrate testing is unavailable, clinicians can still accurately diagnose DKA and initiate appropriate treatment to reduce morbidity and mortality associated with this serious complication of diabetes.