Which laboratory values change when a patient is developing diabetic ketoacidosis?

Laboratory Abnormalities in Developing Diabetic Ketoacidosis

When a patient is developing DKA, expect hyperglycemia (>250 mg/dL), metabolic acidosis (pH <7.3, bicarbonate <15-18 mEq/L), elevated anion gap (>10-12 mEq/L), positive ketones (especially β-hydroxybutyrate), and electrolyte disturbances including paradoxically elevated or normal serum potassium despite total body depletion. 1

Core Metabolic Derangements

Glucose Abnormalities

• Blood glucose >250 mg/dL is the classic threshold for DKA diagnosis, though approximately 10% of cases present as euglycemic DKA with glucose <200 mg/dL (especially with SGLT2 inhibitor use, pregnancy, reduced oral intake, or recent insulin administration) 1, 2
• Hyperglycemia drives osmotic diuresis leading to profound dehydration and hemoconcentration 1

Acid-Base Disturbances

• Venous pH <7.3 is required for diagnosis (venous pH runs approximately 0.03 units lower than arterial, making venous sampling sufficient for monitoring) 1
• Serum bicarbonate <15-18 mEq/L indicates metabolic acidosis severity 1
• Severity stratification by pH:
  • Mild DKA: pH 7.25-7.30, bicarbonate 15-18 mEq/L 1
  • Moderate DKA: pH 7.00-7.24, bicarbonate 10-15 mEq/L 1
  • Severe DKA: pH <7.00, bicarbonate <10 mEq/L 1

Anion Gap Elevation

• Calculate anion gap as [Na⁺] - ([Cl⁻] + [HCO₃⁻]), which should be >10-12 mEq/L in DKA 1
• The elevated anion gap reflects accumulation of unmeasured ketoacids (β-hydroxybutyrate, acetoacetate) 1

Ketone Body Measurements

Preferred Testing Method

• Blood β-hydroxybutyrate (β-OHB) is the gold standard for diagnosis and monitoring, as it measures the predominant and strongest ketoacid in DKA 1, 2
• Normal fasting β-OHB is <0.5 mmol/L; DKA resolution requires normalization to this level 1

Critical Pitfall to Avoid

• Never rely on urine ketone strips or nitroprusside-based tests for diagnosis or monitoring—these only detect acetoacetate and acetone, completely missing β-OHB 1, 2
• During treatment, β-OHB converts to acetoacetate, making nitroprusside tests paradoxically appear worse even as the patient improves 1

Electrolyte Abnormalities

Potassium Disturbances

• Total body potassium is depleted by 3-5 mEq/kg despite normal or elevated initial serum levels due to extracellular shift from acidosis and insulin deficiency 1
• Hyperkalemia occurs in 32.5% of DKA patients at presentation due to hemoconcentration and transcellular shifts 3
• Hypokalemia occurs in 7.5% initially but develops rapidly during treatment as insulin drives potassium intracellularly 3
• Serum potassium is negatively correlated with estimated glomerular filtration rate (eGFR) 3

Sodium Abnormalities

• Measured serum sodium is typically low due to osmotic dilution from hyperglycemia 1
• Correct sodium for hyperglycemia using: [measured Na (mEq/L)] + [glucose (mg/dL) - 100]/100 × 1.6 1
• Corrected sodium is often elevated due to free water losses from osmotic diuresis 1

Other Electrolyte Changes

• Serum phosphorus, magnesium, and calcium are generally elevated at presentation due to hemoconcentration 3
• Chloride may be elevated, contributing to a hyperchloremic component as ketoacids are cleared 1

Renal Function Markers

• Blood urea nitrogen (BUN) and creatinine are elevated reflecting prerenal azotemia from volume depletion 1
• Estimated GFR is significantly lower in DKA patients compared to diabetic controls, and is an important factor affecting serum potassium levels 3
• Renal function deteriorates significantly when DKA occurs, requiring close monitoring 3

Additional Laboratory Findings

Osmolality

• Serum osmolality is elevated and should be calculated or measured directly 1
• Effective osmolality = 2 × [Na] + [glucose]/18 contributes to altered mental status 1

Complete Blood Count

• Leukocytosis is common even without infection due to stress response 1
• Obtain complete blood count with differential to identify infection as a precipitating cause 1

Urinalysis

• Glucosuria (4+) and ketonuria (4+) are typically present 4
• Persistent glucosuria and ketonuria despite serum glucose below renal threshold can indicate ongoing ketoacidosis, especially in euglycemic DKA 4

Monitoring Frequency During Active DKA

• Check electrolytes, glucose, BUN, creatinine, osmolality, and venous pH every 2-4 hours during treatment 1
• Monitor β-hydroxybutyrate every 2-4 hours alongside other parameters, as ketone clearance lags behind glucose normalization 1
• Venous pH and anion gap adequately track acidosis resolution without requiring repeated arterial blood gases 1

Resolution Criteria

DKA is resolved only when ALL of the following are met:

• Glucose <200 mg/dL 1
• Serum bicarbonate ≥18 mEq/L 1
• Venous pH >7.3 1
• Anion gap ≤12 mEq/L 1
• β-hydroxybutyrate normalized to <0.5 mmol/L 1

Special Considerations

Mixed Acid-Base Disorders

• Approximately 23% of DKA cases present with diabetic ketoalkalosis (pH >7.4) due to concurrent metabolic alkalosis and/or respiratory alkalosis 5
• These patients still have elevated anion gap metabolic acidosis and may have severe ketoacidosis (β-OHB ≥3 mmol/L) requiring full DKA treatment despite alkalemic pH 5

Differential Diagnosis Clues

• Alcoholic ketoacidosis presents with normal to mildly elevated glucose (rarely >250 mg/dL) or frank hypoglycemia, distinguishing it from DKA 6
• Starvation ketosis has serum bicarbonate typically ≥18 mEq/L and less severe acidosis than DKA 2