A 28-year-old woman from Mumbai with type 1 diabetes mellitus on insulin therapy presents with a 3-day history of severe diarrhea and reduced oral intake due to acute gastroenteritis. She continued her usual insulin dose. On arrival, she is confused, with rapid shallow breathing (RR 28/min). Blood glucose is 65 mg/dL, pH 7.18, HCO₃⁻ 8 mEq/L, and serum ketones are elevated. Serum insulin level is 8 mIU/L. Which of the following best explains the metabolic derangement in this patient?

## Euglycemic Diabetic Ketoacidosis (euDKA) Pathophysiology ### Clinical Presentation Analysis This case presents a **paradoxical state**: the patient has **ketoacidosis (pH 7.18, HCO₃⁻ 8, elevated ketones) WITH hypoglycemia (65 mg/dL)**. This is **euglycemic DKA**, a rare but dangerous complication in type 1 diabetes. ### Why This Occurs: The Insulin Paradox **Key Point:** The patient received exogenous insulin despite reduced caloric intake. Insulin drives glucose into cells and inhibits hepatic glucose production, causing hypoglycemia. However, insulin does NOT directly inhibit lipolysis and ketogenesis — these are controlled by **glucagon and catecholamines**. ### Step-by-Step Mechanism 1. **Reduced oral intake + continued insulin** → blood glucose falls (hypoglycemia develops) 2. **Hypoglycemia triggers counter-regulatory hormones:** - Glucagon ↑↑ (primary) - Epinephrine ↑↑ (secondary) - Cortisol ↑ (tertiary) 3. **Glucagon and epinephrine activate lipolysis** → free fatty acids released from adipose tissue 4. **Hepatic ketogenesis** → acetoacetate and beta-hydroxybutyrate produced (exogenous insulin cannot suppress this; it only suppresses glucose production) 5. **Result:** Ketoacidosis develops while glucose remains low (because insulin is still present and suppressing hepatic glucose output) ### Why Insulin Level Is Detectable (8 mIU/L) The patient is on exogenous insulin therapy. The serum insulin of 8 mIU/L represents the **injected insulin**, which: - Suppresses hepatic gluconeogenesis and glycogenolysis (keeps glucose low) - Does NOT suppress ketogenesis (which is driven by glucagon and catecholamines) **Clinical Pearl:** In classic DKA, insulin is absent or very low AND glucose is high. In euDKA, insulin is present (from exogenous source) AND glucose is low, but ketones are still high. This is why euDKA is often missed — the low glucose falsely reassures clinicians that "DKA cannot be happening." ### Comparison: DKA vs. euDKA | Feature | Classic DKA | Euglycemic DKA | | --- | --- | --- | | **Blood Glucose** | > 250 mg/dL | < 150 mg/dL (often < 100) | | **Serum Insulin** | Absent/very low | Present (exogenous) | | **Ketones** | ↑↑ (high) | ↑↑ (high) | | **pH** | < 7.30 | < 7.30 | | **Trigger** | Infection, missed insulin | Reduced intake + continued insulin | | **Diagnosis** | Obvious | Often delayed (glucose is low!) | **High-Yield:** euDKA accounts for ~5–10% of DKA presentations in type 1 diabetes. Risk factors include: - Reduced caloric intake (vomiting, diarrhea, fasting) - Continued or excessive insulin dosing - SGLT2 inhibitor use (independent risk factor) - Pregnancy **Mnemonic: KETONE-GLUCOSE MISMATCH** — **K**etones high despite **E**xogenous insulin present, **T**riggered by **O**ral intake **N**ot matching insulin **E**xcess; **G**lucose **L**ow because insulin suppresses hepatic output; **U**nder-recognized because **C**linicians expect high glucose; **O**ften **S**evere because diagnosis delayed; **E**ndocrine counter-regulation drives ketogenesis.