Euglycaemic Ketoacidosis (euDKA) with SGLT2 Inhibitors

Related Subjects: |Metabolic acidosis |Type 1 DM |Type 2 DM |Diabetes in Pregnancy |HbA1c |Diabetic Ketoacidosis (DKA) Adults |Hyperglycaemic Hyperosmolar State (HHS) |Diabetic Nephropathy |Diabetic Retinopathy |Diabetic Neuropathy |Diabetic Amyotrophy |Maturity Onset Diabetes of the Young (MODY) |Diabetes: Complications

⚠️ Euglycaemic Ketoacidosis (euDKA) is a dangerous condition where ketoacidosis occurs despite normal or only mildly elevated glucose. 👉 This may lead to misdiagnosis and undertreatment if not recognised early.

📌 About

• Rare but potentially life-threatening metabolic emergency.
• Most commonly seen in Type 1 Diabetes Mellitus, but also increasingly recognised in SGLT2 inhibitor users.
• Characterised by: ketoacidosis + normal/mild hyperglycaemia (≤13.9 mmol/L or ≤250 mg/dL).

🔥 Precipitants

• Alcohol or illicit drug use.
• Missed/reduced insulin dose.
• SGLT2 inhibitor therapy (empagliflozin, dapagliflozin, etc.).
• Ketogenic or very low carbohydrate diet.
• Pregnancy (increased insulin resistance).
• Previous history of DKA.
• Intercurrent illness: infection, dehydration, vigorous exercise, peri-operative stress.

🧪 Findings

• Glucose: Normal or mildly raised (<13.9 mmol/L / 250 mg/dL).
• Acid–base: Metabolic acidosis with raised anion gap (HCO₃ ≤15 mmol/L, pH ≤7.3).
• Ketones: Raised serum β-hydroxybutyrate (≥3 mmol/L).

👩‍⚕️ Clinical Features

• Polyuria, polydipsia, dehydration.
• Abdominal pain, nausea, vomiting.
• Malaise, dizziness, syncope.
• May mimic sepsis, ACS, or GI disease — ⚠️ high index of suspicion needed.

🔎 Investigations

• FBC, U&E, bone profile, CRP, glucose, serum ketones, venous blood gas (VBG).
• CXR if respiratory signs/symptoms.
• Blood and urine cultures if sepsis suspected.

💉 Management

• Early endocrine consult — specialist input is vital.
• ABC approach with IV access and monitoring.
• Immediately stop SGLT2 inhibitor if on therapy.
• IV fluids for rehydration (0.9% saline initially).
• Carbohydrate replacement (e.g. IV dextrose infusion) to prevent hypoglycaemia during insulin therapy.
• Bolus insulin, then variable rate insulin infusion per DKA protocol (with glucose monitoring).
• Correct electrolytes (especially potassium).

🛡 Prevention

• Educate patients on recognising symptoms and monitoring ketones.
• Advise stopping SGLT2 inhibitors during acute illness, peri-operatively, or when fasting (“sick day rules”).
• Avoid ketogenic/very low carbohydrate diets in insulin-dependent diabetes.

📚 References

• NICE NG17: Type 1 Diabetes in Adults (2022 update).
• Joint British Diabetes Societies (JBDS) guideline on DKA (2020).
• FDA/EMA safety communications on SGLT2 inhibitor–associated euDKA.

💡 Teaching Pearl: Think “Ketones + Acidosis, but Glucose normal” → consider euDKA. Do not be reassured by a normal glucose in a patient on SGLT2 inhibitors with acidosis!

Cases — Euglycaemic Ketoacidosis (euDKA) with SGLT2 Inhibitors 💊

• Case 1 — euDKA after Surgery 🏥: A 59-year-old man with type 2 diabetes on empagliflozin undergoes elective hip replacement. On day 2 post-op, he develops nausea, abdominal pain, and Kussmaul breathing. Blood glucose: 8.5 mmol/L (normal range), ketones: 4.8 mmol/L, pH 7.22. Diagnosis: Euglycaemic DKA precipitated by perioperative stress and SGLT2 inhibitor. Management: Stop SGLT2 inhibitor; IV insulin + dextrose infusion; fluid resuscitation; monitor ketones and electrolytes closely.
• Case 2 — euDKA with Intercurrent Illness 🤒: A 47-year-old woman with T2DM on dapagliflozin presents with vomiting and reduced oral intake during a viral illness. She feels weak, with fruity breath. Blood glucose: 9.2 mmol/L, ketones: 5.2 mmol/L, pH 7.18. Diagnosis: Euglycaemic DKA triggered by dehydration and infection while on SGLT2 inhibitor. Management: Stop SGLT2 inhibitor; IV fluids, insulin infusion with dextrose; potassium replacement as required; infection treatment.

Teaching Commentary 🧠

Euglycaemic DKA = DKA with normal or mildly raised glucose (<11 mmol/L). - Mechanism: SGLT2 inhibitors increase glycosuria → lower plasma glucose but promote ketosis, especially in fasting, surgery, or illness. - Clues: Metabolic acidosis, high ketones, but glucose not markedly raised. - Management: Stop SGLT2 inhibitor, give IV insulin + dextrose, fluids, and correct electrolytes. ⚠️ Always stop SGLT2 inhibitors before major surgery or during acute illness ("sick day rules").