Can DKA Elevate Procalcitonin?
Yes, diabetic ketoacidosis (DKA) can elevate procalcitonin levels even in the absence of bacterial infection, but the degree of elevation is typically modest compared to when infection is present. 1, 2
Understanding Procalcitonin Elevation in DKA
Baseline Elevation Without Infection
In DKA patients without proven bacterial infection, median procalcitonin levels are approximately 0.52 ng/mL, which is above the traditional normal range but substantially lower than in infected patients. 1
DKA itself can trigger a systemic inflammatory response syndrome (SIRS), leading to modest procalcitonin elevation through the release of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) even without infection. 3
The metabolic derangements of DKA—including severe acidosis, dehydration, and stress hormone excess—create an inflammatory milieu that can independently stimulate procalcitonin production. 4, 3
Procalcitonin in DKA With Infection
When bacterial infection is present in DKA, procalcitonin levels are significantly higher, with median values around 3.58 ng/mL, demonstrating a clear distinction from non-infected DKA. 1
A procalcitonin cutoff of 1.44 ng/mL provides optimal diagnostic performance for distinguishing infected from non-infected DKA, with 90% sensitivity and 76% specificity (AUC 0.87). 1
All patients with both procalcitonin >1.44 ng/mL AND fever had proven bacterial infection, while no afebrile patient with procalcitonin <1.44 ng/mL had documented infection. 1
Clinical Algorithm for Interpreting Procalcitonin in DKA
High Probability of Infection
- Procalcitonin >1.44 ng/mL + fever (>38°C): 100% positive predictive value for bacterial infection; initiate empiric antibiotics immediately. 1
Intermediate Probability
- Procalcitonin >1.44 ng/mL without fever OR fever without elevated procalcitonin: 46% of these patients have proven infection; consider empiric antibiotics while awaiting cultures, especially if other clinical signs suggest infection. 1
Low Probability of Infection
- Procalcitonin <1.44 ng/mL + afebrile: No documented infections in this group; withhold antibiotics unless clinical deterioration occurs. 1
Alternative Marker: Procalcitonin-to-Lactate Ratio
- A procalcitonin-to-lactic acid ratio (PLR) >0.438 combined with leukocyte count >10×10⁹/L provides additional diagnostic value for infection in DKA, regardless of diabetes type. 2
Important Caveats
Traditional infection markers (WBC count, neutrophil count, neutrophil-to-lymphocyte ratio) do NOT reliably distinguish infected from non-infected DKA at admission, as DKA itself causes leukocytosis through stress hormone release. 1
C-reactive protein (CRP) is elevated in severe DKA without infection and correlates with pro-inflammatory cytokines, making it unreliable for infection diagnosis in this context. 3
Hypothermia (<36°C) does NOT differentiate infected from non-infected DKA, contrary to its utility in other septic conditions. 1
Approximately 50% of DKA cases are triggered by bacterial infections (urinary tract infections and pneumonia being most common), making infection detection critical for appropriate antibiotic stewardship. 5
Practical Pitfall to Avoid
Do not reflexively start antibiotics based solely on modest procalcitonin elevation (0.5–1.4 ng/mL) in DKA patients without fever or other infection signs, as this represents the inflammatory response to DKA itself rather than bacterial infection. 1 Conversely, do not withhold antibiotics when procalcitonin is >1.44 ng/mL with fever, as this combination has 100% specificity for proven infection. 1