A 28-year-old woman presents with a 3-week history of polyuria, polydipsia, and weight loss of 4 kg. She reports feeling unusually fatigued and has noticed fruity-smelling breath for the past 2 days. On examination, she appears ill, with respiratory rate 28/min and deep, labored breathing. Blood glucose is 487 mg/dL, arterial pH 7.21, HCO₃⁻ 12 mEq/L, and serum ketones are strongly positive. C-peptide level is <0.5 ng/mL (normal 0.8–3.1). What is the most likely diagnosis?

Explanation

## Clinical Presentation Analysis **Key Point:** This patient presents with acute onset polyuria, polydipsia, weight loss, and fruity breath — classic signs of **diabetic ketoacidosis (DKA)**, which is the typical presentation of Type 1 diabetes mellitus. ### Diagnostic Findings | Feature | This Case | Type 1 DKA | Type 2 HHS | |---------|-----------|-----------|----------| | **Age of onset** | 28 years (young) | Typically <30 years | Usually >50 years | | **Symptom duration** | 3 weeks (acute) | Days to weeks | Insidious (weeks–months) | | **Respiratory pattern** | Deep, labored (Kussmaul) | Present in DKA | Absent in HHS | | **pH** | 7.21 (acidemia) | <7.30 in DKA | >7.30 in HHS | | **HCO₃⁻** | 12 mEq/L (low) | <15 in DKA | >15 in HHS | | **Serum ketones** | Strongly positive | Positive in DKA | Absent/minimal in HHS | | **C-peptide** | <0.5 (very low) | Low/absent in Type 1 | Normal/high in Type 2 | | **Osmolality** | Moderate elevation | Moderate | Severe (>320 mOsm/kg) | **High-Yield:** C-peptide <0.5 ng/mL indicates **absent endogenous insulin secretion**, confirming Type 1 diabetes. In Type 2, C-peptide would be normal or elevated despite hyperglycemia. ### Pathophysiology of Type 1 DKA 1. **Autoimmune destruction** of pancreatic β-cells → absolute insulin deficiency 2. **Unopposed lipolysis** → free fatty acid mobilization 3. **Hepatic ketogenesis** → acetoacetate, β-hydroxybutyrate, acetone 4. **Metabolic acidosis** → ↓ pH, ↓ HCO₃⁻, positive anion gap 5. **Kussmaul respiration** (compensatory hyperventilation) → fruity breath (acetone) **Clinical Pearl:** Kussmaul breathing with fruity odor is pathognomonic for DKA and distinguishes it from HHS, where respiration is typically normal. ### Why Type 1 and Not Type 2? - **Age:** Young adult (28 years) — Type 1 peak incidence is <30 years - **Acuity:** Rapid symptom onset (3 weeks) — Type 1 presents acutely; Type 2 is insidious - **Ketosis:** Strong positive serum ketones — Type 1 causes DKA; Type 2 rarely develops ketosis (residual insulin suppresses lipolysis) - **C-peptide:** <0.5 ng/mL — indicates no functional β-cells (Type 1 hallmark) - **Acidosis:** pH 7.21, HCO₃⁻ 12 — metabolic acidosis with Kussmaul breathing is DKA, not HHS **Mnemonic: ACID-K** — **A**cute onset, **C**-peptide low, **I**nsulin absent, **D**eep breathing (Kussmaul), **K**etones positive = Type 1 DKA. ## Management Implications - **Immediate:** IV fluids (0.9% saline), insulin infusion (0.1 U/kg/hr), electrolyte monitoring - **Long-term:** Insulin replacement (basal-bolus or pump therapy), diabetes education, autoimmune screening if indicated [cite:Harrison 21e Ch 417]