Can diabetic ketoacidosis (DKA) cause elevated lactate levels?

Can DKA Cause Elevated Lactate?

Yes, diabetic ketoacidosis (DKA) commonly causes elevated lactate levels, with hyperlactatemia (>2 mmol/L) present in approximately 88% of DKA cases at presentation. 1

Mechanisms of Lactate Elevation in DKA

The elevated lactate in DKA occurs through several pathophysiological mechanisms:

• Increased gluconeogenic precursors: The combination of insulin deficiency and elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) leads to enhanced protein catabolism, increased amino acid flux from muscle, and elevated blood pyruvate and lactate concentrations 2

• Tissue hypoperfusion: Severe dehydration and hypovolemia from osmotic diuresis can cause inadequate tissue perfusion, contributing to anaerobic metabolism and lactate production 3

• Metabolic stress: The hyperglycemic crisis itself creates a metabolic environment that promotes lactate generation 1

Clinical Patterns and Time Course

Lactate elevation in DKA follows two distinct patterns:

• Rapid resolution (72% of cases): Lactate normalizes within 2.6 hours with standard DKA treatment, with an aggregate decay half-life of 2.29 hours 1

• Prolonged elevation (28% of cases): Hyperlactatemia persists beyond 12 hours, more commonly in females with relative anemia (hemoglobin 131 vs 155 g/L) and lower nadir glucose concentrations (5.2 vs 8.0 mmol/L) 1

Important Clinical Distinctions

DKA must be differentiated from pure lactic acidosis, which is a separate cause of high anion-gap metabolic acidosis 3:

• In DKA, the primary acidosis is from ketoacids (β-hydroxybutyrate and acetoacetate), with lactate as a secondary contributor 3
• Pure lactic acidosis presents with normal or mildly elevated glucose and absent or minimal ketonemia 3
• Measurement of blood lactate levels helps distinguish these conditions when the clinical picture is unclear 3

Treatment-Related Lactate Changes

Lactate levels may paradoxically increase during DKA treatment:

• A transient rise in lactate is commonly observed after initiating therapy 4
• In some cases, ketoacidosis is replaced by lactic acidosis during treatment, usually associated with serious underlying disorders and poor prognosis 4
• Refeeding syndrome from insulin therapy can cause rising lactate due to thiamine and phosphate deficiency 5

Clinical Pitfalls to Avoid

Aggressive glucose correction increases risk of prolonged hyperlactatemia:

• Patients whose glucose is corrected to very low levels (nadir <5.2 mmol/L) are at higher risk for persistent lactate elevation 1
• Consider limiting initial hyperglycemia correction to ≥11 mmol/L to reduce this risk 1

Monitor for concurrent lactic acidosis:

• If lactate remains severely elevated despite resolving ketoacidosis, search for alternative causes including sepsis, tissue ischemia, metformin use, or other toxins 3
• Rising lactate during treatment warrants evaluation for complications such as infection, shock, or metabolic derangements 4, 5