What is euglycemic diabetic ketoacidosis, how is it diagnosed in diabetic patients (especially those on sodium‑glucose cotransporter‑2 inhibitors), and what is the recommended management?

Euglycemic Diabetic Ketoacidosis

Definition and Core Diagnostic Criteria

Euglycemic diabetic ketoacidosis (euglycemic DKA) is a life-threatening metabolic emergency characterized by metabolic acidosis (pH <7.3 and bicarbonate <18 mEq/L), elevated ketones, and blood glucose <200-250 mg/dL—making it easily missed because the hallmark hyperglycemia of typical DKA is absent. 1

The diagnosis requires all three components simultaneously:

• Metabolic acidosis: arterial or venous pH <7.3 AND serum bicarbonate <18 mEq/L 1
• Ketosis: elevated blood β-hydroxybutyrate (preferred) or positive urine ketones 1
• Euglycemia or mild hyperglycemia: plasma glucose <200-250 mg/dL 1
• Plus: documented hyperglycemia at any point OR known diabetes history 1

Approximately 10% of all DKA presentations are euglycemic. 1

High-Risk Populations and Precipitating Factors

SGLT2 Inhibitors: The Leading Modern Cause

SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) are the most common cause of euglycemic DKA in contemporary practice. 2 These medications promote urinary glucose excretion independent of insulin, allowing ketoacidosis to develop while maintaining relatively normal blood glucose levels. 2

• The incidence is 0.6-4.9 events per 1,000 patient-years with a relative risk of 2.46 compared to placebo. 2
• Critical pitfall: The risk can persist for days after discontinuation—cases have occurred 5 days after stopping the medication before surgery. 3

Other High-Risk Scenarios

Insulin dose reduction or omission (>20% reduction) is a critical precipitating factor. 2 This is particularly dangerous when:

• Transitioning from insulin to SGLT2 inhibitors 4
• Patients with latent autoimmune diabetes in adults (LADA) misdiagnosed as type 2 diabetes 2, 5
• Unrecognized type 1 diabetes in adults (5-10% of adult-onset diabetes) 2

Reduced caloric intake or prolonged fasting: 2

• Very-low-carbohydrate or ketogenic diets 2
• Poor oral intake during acute illness 2
• Preoperative fasting 3
• Intentional weight loss with severe caloric restriction 5

Acute physiologic stress: 6

• Infection (especially urinary tract infections) 7
• Myocardial infarction 2
• Major surgery 3
• Volume depletion and dehydration 2

Pregnancy in women with pregestational diabetes. 2

Other medications: 2

• Corticosteroids 2
• Atypical antipsychotics 2

Alcohol consumption (excessive intake). 2

Diagnostic Approach

Initial Laboratory Workup

When euglycemic DKA is suspected, obtain immediately: 1

• Blood glucose (may be normal or only mildly elevated)
• Arterial or venous blood gas for pH and bicarbonate
• Serum β-hydroxybutyrate (preferred ketone measurement)
• Basic metabolic panel with calculated anion gap (typically >10-12 mEq/L)
• Blood urea nitrogen and creatinine
• Serum osmolality
• Complete blood count with differential
• Urinalysis (will show glucosuria and ketonuria despite normal blood glucose)
• Electrocardiogram

Critical Diagnostic Pitfall: Ketone Measurement

Blood β-hydroxybutyrate is the only reliable test for diagnosing and monitoring euglycemic DKA. 1

Never rely on urine ketone strips or nitroprusside-based tests because: 1

• They only detect acetoacetate and acetone, NOT β-hydroxybutyrate
• β-hydroxybutyrate is the predominant ketone in DKA
• During treatment, β-hydroxybutyrate converts to acetoacetate, making nitroprusside tests falsely suggest worsening ketosis when the patient is actually improving

Severity Classification

Classify severity based on acidosis degree: 1

• Mild: pH 7.25-7.30, bicarbonate 15-18 mEq/L, anion gap >10 mEq/L, alert
• Moderate: pH 7.00-7.24, bicarbonate 10-<15 mEq/L, anion gap >12 mEq/L, alert to drowsy
• Severe: pH <7.00, bicarbonate <10 mEq/L, anion gap >12 mEq/L, stupor or coma

Differential Diagnosis

Rule out other causes of high anion gap metabolic acidosis: 1

• Alcoholic ketoacidosis: history of alcohol use, glucose typically normal to mildly elevated (rarely >250 mg/dL) or hypoglycemic, less severe acidosis 1
• Starvation ketosis: serum bicarbonate typically ≥18 mEq/L, less severe acidosis, prolonged fasting history 1
• Lactic acidosis 1
• Toxic ingestions (salicylates, methanol, ethylene glycol) 1

Management Algorithm

Acute Treatment

Continue insulin therapy despite normal glucose levels—this is the key therapeutic principle. 8

1. Aggressive IV fluid resuscitation 8

   • Address volume depletion first

2. Insulin infusion 8

   • Start IV regular insulin (typical DKA protocol)
   • Do NOT stop insulin when glucose normalizes

3. Add dextrose to IV fluids once glucose approaches normal 8

   • Continue insulin infusion while adding dextrose 5% or 10% in water
   • This allows continued insulin administration to suppress ketogenesis without causing hypoglycemia

4. Potassium replacement as needed 4

   • Monitor closely as insulin drives potassium intracellularly

5. Monitor resolution based on metabolic parameters, NOT glucose: 8

   • pH normalization (>7.3)
   • Bicarbonate ≥18 mEq/L
   • Anion gap closure
   • β-hydroxybutyrate normalization

6. Slower transition to subcutaneous insulin 8

   • Continue IV insulin longer than typical DKA to prevent relapse
   • Ensure adequate overlap with subcutaneous insulin before discontinuing IV infusion

Resolution Criteria

Euglycemic DKA is resolved when: 1

• Glucose <200 mg/dL (may already be met)
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Anion gap normalized
• β-hydroxybutyrate normalized

Prevention Strategies

For Patients on SGLT2 Inhibitors

Discontinue SGLT2 inhibitors at least 3 days before elective surgery or procedures requiring fasting. 2 Given that risk can persist beyond this timeframe 3, consider extending to 5-7 days for major surgery.

Temporarily discontinue during: 2

• Acute illness with poor oral intake
• Dehydration or volume depletion
• Prolonged fasting
• Any situation requiring significant insulin dose reduction

Avoid substantial insulin dose reductions (>20%) when initiating SGLT2 inhibitors. 2

Initiate SGLT2 inhibitors in collaboration with diabetes specialists for patients on complex insulin regimens or with labile glucose control. 2

Patient Education

Educate all patients on SGLT2 inhibitors about euglycemic DKA risk. 2 Instruct them to:

• Seek immediate care for nausea, vomiting, abdominal pain, or generalized weakness 2
• Check ketones (blood or urine) during high-risk situations 2
• Understand that normal blood glucose does NOT rule out DKA 7
• Stop SGLT2 inhibitor and seek medical attention immediately if ketoacidosis symptoms develop 6

Clinical Vigilance

Check blood pH and ketones in ill diabetic patients regardless of blood glucose levels. 7 The normal glucose masquerades the underlying ketoacidosis, creating a diagnostic and therapeutic dilemma. 7

Consider screening for LADA (GAD65 antibodies, C-peptide, ZnT8 antibodies) in patients with apparent type 2 diabetes who develop euglycemic DKA, especially if on SGLT2 inhibitors. 5