What is euglycemic diabetic ketoacidosis?

Euglycemic Diabetic Ketoacidosis (Euglycemic DKA)

Euglycemic DKA is diabetic ketoacidosis occurring with plasma glucose levels below 200 mg/dL (11.1 mmol/L), representing approximately 10% of all DKA presentations and requiring the same metabolic criteria as classic DKA—ketoacidosis and elevated anion gap—but without marked hyperglycemia. 1

Definition and Diagnostic Criteria

Euglycemic DKA meets all standard DKA criteria except for the glucose threshold:

• Metabolic acidosis with pH typically <7.3 1
• Elevated serum ketones (β-hydroxybutyrate) or positive urine ketones 1, 2
• Elevated anion gap metabolic acidosis 2, 3
• **Plasma glucose <200 mg/dL** (distinguishing it from classic DKA where glucose is typically >250 mg/dL) 1
• Prior history of diabetes (required when glucose is not elevated) 1

The American Diabetes Association emphasizes that DKA diagnosis requires either the presence of hyperglycemia OR prior history of diabetes, specifically to capture euglycemic presentations. 1

Pathophysiology

Euglycemic DKA requires absolute insulin deficiency combined with factors that prevent marked hyperglycemia 1:

• Continued urinary glucose excretion (particularly with SGLT2 inhibitors) prevents glucose accumulation despite ketogenesis 4, 5
• Reduced carbohydrate intake or starvation limits substrate for glucose production 1, 3
• Preserved residual insulin secretion may be sufficient to prevent severe hyperglycemia but inadequate to suppress lipolysis and ketogenesis 3

Major Risk Factors and Precipitants

The American Diabetes Association identifies specific conditions associated with euglycemic DKA 1:

• SGLT2 inhibitor therapy (dapagliflozin, empagliflozin, canagliflozin)—the most common modern cause 1, 2, 6
• Pregnancy—up to 2% of pregnancies with pregestational diabetes develop DKA, often euglycemic 1
• Reduced food intake or starvation 1, 3
• Alcohol use 1
• Liver failure 1
• Insulin pump failure 3
• Intercurrent illness with nausea/vomiting causing reduced oral intake 2, 3

SGLT2 Inhibitor-Associated Euglycemic DKA

The American Diabetes Association notes that while DKA is uncommon with SGLT2 inhibitors in type 2 diabetes (0.6–4.9 events per 1,000 patient-years), the relative risk is significantly elevated at 2.46 compared to placebo. 1

Critical precipitating factors with SGLT2 inhibitors include 1:

• Very-low-carbohydrate or ketogenic diets
• Prolonged fasting or reduced caloric intake
• Dehydration
• Excessive alcohol intake
• Presence of autoimmunity (latent autoimmune diabetes)
• Major surgery or acute illness

A critical pitfall: The risk of euglycemic DKA can persist for days after SGLT2 inhibitor discontinuation due to prolonged urinary glucose excretion and drug effects. 5 One case demonstrated EDKA occurring 5 days after stopping the medication before cardiac surgery, with persistent ketonemia and glucosuria postoperatively. 5

Clinical Presentation and Diagnostic Challenges

The absence of marked hyperglycemia makes euglycemic DKA easily missed in the emergency department. 2, 6

Classic DKA symptoms are present 2, 3:

• Nausea and vomiting
• Abdominal pain
• Dyspnea and Kussmaul respirations
• Lethargy or altered mental status
• Clinical dehydration
• Body weakness

The diagnostic challenge: Normal or mildly elevated glucose levels (often 140–200 mg/dL) cause clinicians to dismiss DKA from the differential diagnosis, leading to delayed recognition and treatment. 2, 6, 3

Essential Diagnostic Approach

In any diabetic patient presenting with nausea, vomiting, abdominal pain, dyspnea, or lethargy—particularly those on SGLT2 inhibitors—check blood pH, serum ketones (β-hydroxybutyrate preferred), and anion gap regardless of glucose levels. 2, 4, 3

The American Diabetes Association recommends measuring β-hydroxybutyrate rather than using the nitroprusside method for more accurate ketone detection. 7

Key laboratory findings 2, 3:

• Arterial pH <7.3 with elevated anion gap
• Elevated serum β-hydroxybutyrate or positive urine ketones
• Serum bicarbonate typically <18 mEq/L
• Blood glucose 140–200 mg/dL (may be entirely normal)
• Normal serum lactate (helps exclude lactic acidosis)

Treatment Principles

Management follows standard DKA protocols with one critical modification: dextrose-containing fluids must be started earlier to prevent hypoglycemia while continuing insulin therapy. 6, 4

Initial Management 6, 4:

• Intravenous insulin infusion at standard DKA dosing (0.1 units/kg/hour after 0.1 units/kg bolus)
• Dextrose-containing IV fluids (5% or 10% dextrose) started immediately or when glucose approaches 200 mg/dL
• Aggressive IV hydration with isotonic saline for volume repletion
• Potassium replacement (20–30 mEq/L once K+ ≥3.3 mEq/L and adequate renal function confirmed)

Monitoring 4:

• Serial blood gases to track pH and bicarbonate normalization
• Anion gap and serum ketones (β-hydroxybutyrate) every 2–4 hours
• Blood glucose hourly initially
• Serum electrolytes every 2–4 hours

Resolution Criteria 4:

• Anion gap normalized (<12 mEq/L)
• Serum ketones cleared or significantly reduced
• pH >7.3 and bicarbonate >18 mEq/L
• Patient able to tolerate oral intake

A critical pitfall in euglycemic DKA: Transitioning to subcutaneous insulin too quickly can cause relapse of ketoacidosis. Continue IV insulin until anion gap normalizes and ketones clear, even if glucose is normal. 4

Prevention Strategies

For patients on SGLT2 inhibitors, the American Diabetes Association recommends 1:

• Counseling on signs and symptoms of DKA
• Instructions to seek immediate medical attention if symptoms develop
• Measuring urine or blood ketones when symptomatic, particularly with glucose >200 mg/dL
• Never stopping basal insulin even when not eating
• Discontinuing SGLT2 inhibitors during acute illness, prolonged fasting, or before major surgery
• Avoiding very-low-carbohydrate diets and excessive alcohol

For pregnant individuals with diabetes, counsel on DKA signs/symptoms and the possibility of euglycemic presentation, with instructions to seek immediate care if concerned. 1

Key Clinical Pearls

• Euglycemic DKA accounts for approximately 10% of all DKA cases but is frequently missed due to normal glucose levels 1
• SGLT2 inhibitors are the most common modern precipitant in type 2 diabetes, with risk persisting days after discontinuation 1, 5
• Pregnancy is a high-risk state for euglycemic DKA, with up to 2% of pregestational diabetes pregnancies affected 1
• Check ketones and pH in all symptomatic diabetic patients regardless of glucose level, especially those on SGLT2 inhibitors 2, 3
• Treatment requires insulin plus dextrose to clear ketones while preventing hypoglycemia 6, 4