A 62-year-old woman with type 2 diabetes mellitus on metformin and glibenclamide presents with a 5-day history of progressive confusion, weakness, and polyuria. Her family reports she has had recurrent vomiting and has not been eating well. On examination, she is alert but disoriented, respiratory rate 16/min (not laboured), blood pressure 98/60 mmHg, heart rate 118/min, and skin turgor is poor. Capillary refill time is 3 seconds. Laboratory investigations show: blood glucose 1020 mg/dL, arterial pH 7.32, HCO₃⁻ 18 mEq/L, anion gap 12, serum sodium 122 mEq/L, serum osmolality 385 mOsm/kg, serum potassium 5.8 mEq/L, and serum creatinine 2.2 mg/dL. Urine dipstick shows no ketones and no protein. What is the most likely diagnosis and the key distinguishing feature from DKA?

Explanation

## Diagnosis: Hyperglycaemic Hyperosmolar State (HHS) **Key Point:** HHS is characterized by **severe hyperglycaemia (usually >600 mg/dL), profound dehydration, hyperosmolality (>320 mOsm/kg), and ABSENT or minimal ketosis**. This patient's glucose is 1020 mg/dL, osmolality is 385 mOsm/kg, and urine dipstick shows NO ketones — classic HHS. ## Differential: DKA vs HHS | Feature | DKA | HHS | |---------|-----|-----| | **Glucose** | 250–600 mg/dL | >600 mg/dL (often >1000) | | **pH** | <7.30 (often <7.20) | >7.30 (mild acidosis or normal) | | **HCO₃⁻** | <15 mEq/L | >15 mEq/L | | **Anion gap** | >12 (elevated) | Normal (8–12) | | **Ketones** | 4+ (large) | Absent or trace | | **Osmolality** | <320 mOsm/kg | >320 mOsm/kg (often >350) | | **Kussmaul breathing** | Present (fruity breath) | Absent | | **Typical patient** | Type 1 DM, young | Type 2 DM, elderly | | **Precipitant** | Infection, insulin omission | Infection, dehydration, poor intake | **High-Yield:** The **anion gap** is the key discriminator: DKA has **elevated anion gap** (>12) due to accumulation of β-hydroxybutyrate and acetoacetate; HHS has **normal anion gap** (8–12) because there is no significant ketoacid accumulation. ### Pathophysiology of HHS 1. **Residual insulin** in type 2 DM is sufficient to suppress lipolysis and ketone production 2. But it is **insufficient to lower glucose** adequately 3. Result: **Severe hyperglycaemia WITHOUT ketosis** 4. Osmotic diuresis leads to profound volume depletion and hyperosmolality 5. Altered mental status (confusion, disorientation) is common due to hyperosmolality ### This Patient's Findings - **Glucose 1020 mg/dL** — extreme hyperglycaemia - **Osmolality 385 mOsm/kg** — severe hyperosmolality (normal <310) - **Anion gap 12** — normal, not elevated - **HCO₃⁻ 18 mEq/L** — only mildly reduced - **pH 7.32** — mild acidosis (not severe) - **NO ketones on urine dipstick** — the defining feature - **Severe dehydration** — poor skin turgor, delayed capillary refill, hypotension, tachycardia - **Altered mental status** — due to hyperosmolality, not acidosis ```mermaid flowchart TD A[Severe Hyperglycaemia]:::outcome --> B{Ketones present?}:::decision B -->|Yes, 3-4+| C[DKA]:::outcome B -->|No or trace| D{Osmolality?}:::decision D -->|>320 mOsm/kg| E[HHS]:::outcome D -->|<320 mOsm/kg| F[Hyperglycaemic crisis, other cause]:::outcome C --> G[Elevated anion gap metabolic acidosis]:::action E --> H[Normal anion gap, mild acidosis, profound dehydration]:::action ``` **Clinical Pearl:** HHS is more common in elderly patients with type 2 DM and carries higher mortality (5–15%) than DKA (1–5%) due to age, comorbidities, and delayed presentation. Altered mental status in HHS is due to **hyperosmolality** (not acidosis), so correction of osmolality is critical. **Mnemonic: "HHS = High glucose, High osmolality, No ketones"** [cite:Harrison 21e Ch 396]