Diagnosing Euglycemic Diabetic Ketoacidosis
Euglycemic DKA is diagnosed when blood glucose is <250 mg/dL (some sources use <200 mg/dL) in the presence of metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L), elevated anion gap (>10-12 mEq/L), and positive serum or urine ketones. 1, 2, 3, 4
Core Diagnostic Criteria
The diagnosis requires all of the following laboratory findings:
- Blood glucose <250 mg/dL (or <200 mg/dL by some definitions) - this is the key distinguishing feature from typical DKA 1, 3, 4, 5
- Arterial pH <7.3 (venous pH typically 0.03 units lower is acceptable) 1, 2
- Serum bicarbonate <18 mEq/L 1, 2
- Anion gap >10-12 mEq/L (calculated as Na+ minus [Cl- + HCO3-]) 1, 2
- Positive ketones in blood or urine 1, 2, 3
Essential Laboratory Workup
Obtain the following tests immediately upon suspicion:
- Plasma glucose 6, 2
- Arterial or venous blood gas for pH assessment 6, 2
- Complete metabolic panel including electrolytes, BUN, creatinine 6, 2
- Serum ketones (β-hydroxybutyrate is preferred over nitroprusside method) 1, 2
- Calculated anion gap and serum osmolality 6, 2
- Urinalysis for ketones 6, 2
- Complete blood count with differential 1, 2
- Electrocardiogram 6, 2
Critical Diagnostic Pitfall
The normal or near-normal glucose level masks the underlying ketoacidosis, leading to delayed diagnosis and treatment. 3, 4, 5 You must check blood pH and ketones in any ill diabetic patient regardless of glucose levels, especially if they present with nausea, vomiting, malaise, or fatigue. 3, 5
Preferred Ketone Measurement
Direct measurement of β-hydroxybutyrate in blood is the preferred method for monitoring DKA. 2 The nitroprusside method only measures acetoacetic acid and acetone, not β-hydroxybutyrate (the predominant ketone in DKA), and can be misleading during treatment as β-hydroxybutyrate converts to acetoacetic acid. 1, 2
Common Etiologies to Identify
When euglycemic DKA is diagnosed, immediately investigate these precipitating factors:
- SGLT2 inhibitor use (canagliflozin, dapagliflozin, empagliflozin) - the most important modern cause 1, 6, 2, 4, 7, 5
- Starvation or severe carbohydrate restriction (including ketogenic diets) 8, 4, 5
- Recent insulin use that lowered glucose but didn't prevent ketosis 3, 4
- Pregnancy 4, 5
- Heavy alcohol consumption 4, 5
- Chronic liver disease 4, 5
- Infection (urinary tract infection, sepsis) 3, 5
- Insulin pump failure 3
- Nausea/vomiting leading to decreased oral intake 3, 5
Differential Diagnosis to Exclude
Rule out other causes of high anion gap metabolic acidosis:
- Lactic acidosis (measure blood lactate) 1
- Salicylate toxicity (measure serum salicylate) 1
- Methanol or ethylene glycol ingestion (check osmolar gap, look for calcium oxalate crystals in urine for ethylene glycol) 1
- Chronic renal failure (typically causes hyperchloremic acidosis) 1
Monitoring Parameters
Once diagnosed, draw blood every 2-4 hours for:
- Serum electrolytes 1, 6, 2
- Glucose 1, 6, 2
- BUN and creatinine 1, 6, 2
- Osmolality 1, 6, 2
- Venous pH 1, 6, 2
- Blood glucose every 1-2 hours initially 6, 2
Continuous cardiac monitoring is necessary due to electrolyte shifts and arrhythmia risk. 6
Resolution Criteria
Euglycemic DKA is resolved when ALL of the following are achieved:
- Glucose <200 mg/dL 1, 6, 2
- Serum bicarbonate ≥18 mEq/L 6, 2
- Venous pH >7.3 6, 2
- Anion gap ≤12 mEq/L 6, 2
Key Clinical Pearl
In patients taking SGLT2 inhibitors, discontinue the medication 3-4 days before any planned surgery to prevent euglycemic DKA. 1, 6, 2 SGLT2 inhibitors cause increased urinary glucose excretion, maintaining lower glucose levels while ketoacidosis develops unchecked. 4, 5