A 62-year-old woman with type 2 diabetes mellitus presents with a 5-day history of progressive confusion, weakness, and polydipsia. She lives alone and has not eaten properly for 2 days. On examination: BP 95/55 mmHg, HR 112/min, RR 18/min, skin turgor reduced, mucous membranes dry. Capillary blood glucose 680 mg/dL. Laboratory results: arterial pH 7.32, HCO₃⁻ 18 mEq/L, serum sodium 152 mEq/L, serum potassium 5.2 mEq/L, serum osmolality 338 mOsm/kg, anion gap 12 mEq/L, blood urea nitrogen 68 mg/dL, serum creatinine 2.8 mg/dL. Urine ketones are negative. What is the most likely diagnosis?

Explanation

## Diagnosis: Hyperosmolar Hyperglycemic State (HHS) ### Differential Diagnosis: DKA vs HHS | Feature | DKA | HHS | |---------|-----|-----| | **Glucose** | Usually 250–600 mg/dL | Usually >600 mg/dL (often >1000) | | **Osmolality** | <320 mOsm/kg | >320 mOsm/kg (often >330) | | **pH** | <7.35 (often <7.2) | >7.30 (mild acidosis or normal) | | **HCO₃⁻** | <18 mEq/L (often <10) | >18 mEq/L (often 15–20) | | **Anion gap** | >12 (high) | <12 (normal) | | **Ketones** | **Strongly positive** | **Negative or trace** | | **Typical patient** | Type 1 DM, young | Type 2 DM, elderly | | **Precipitant** | Insulin omission, infection | Infection, dehydration, medication | **Key Point:** This patient has **HHS**, not DKA, because: 1. **Urine ketones are NEGATIVE** — hallmark distinguishing feature 2. **Anion gap is normal (12)** — no significant ketoacidosis 3. **Serum osmolality 338 mOsm/kg** — markedly elevated (>320) 4. **pH 7.32** — mild acidosis, not severe 5. **HCO₃⁻ 18 mEq/L** — at lower end of normal, not severely depressed 6. **Type 2 diabetes, elderly, dehydration** — classic HHS demographics ### Pathophysiology of HHS ```mermaid flowchart TD A[Type 2 DM + Dehydration/Infection]:::outcome --> B[Hyperglycemia]:::outcome B --> C[Osmotic diuresis]:::action C --> D[Severe volume depletion]:::urgent D --> E[Impaired renal glucose clearance]:::action E --> F[Extreme hyperglycemia >600 mg/dL]:::urgent F --> G[Serum osmolality >320 mOsm/kg]:::urgent G --> H[CNS dysfunction: confusion, altered mental status]:::outcome I[Residual insulin secretion]:::action --> J[Suppresses ketogenesis]:::action J --> K[Negative ketones, normal anion gap]:::outcome ``` **Clinical Pearl:** HHS is often called "nonketotic" because residual insulin secretion (even if inadequate to control glucose) is sufficient to suppress ketone production. In contrast, DKA occurs when insulin is completely absent (type 1 DM or severe insulin deficiency). ### Acute Kidney Injury in This Case **High-Yield:** The elevated BUN (68 mg/dL) and creatinine (2.8 mg/dL) indicate **acute kidney injury**, likely prerenal (volume depletion + hypotension) superimposed on chronic kidney disease. - BUN:Cr ratio = 68:2.8 ≈ 24 (>20 suggests prerenal azotemia) - Severe dehydration (dry mucous membranes, reduced skin turgor, hypotension) is the mechanism ### Management Principles for HHS 1. **Aggressive fluid resuscitation** — 0.9% saline at 500–1000 mL/hr (more cautious than DKA due to older age, cardiac/renal comorbidity) 2. **Lower glucose more slowly** — target 50–100 mg/dL/hr decline (rapid correction risks cerebral edema) 3. **Insulin infusion** — 0.05–0.1 units/kg/hr (lower than DKA because osmolality is the primary problem) 4. **Monitor electrolytes closely** — hypokalemia develops as insulin drives K⁺ intracellularly 5. **Treat underlying precipitant** — infection, medication review, etc. **Warning:** HHS has higher mortality (5–15%) than DKA (1–5%) due to older age, comorbidities, and delayed presentation. [cite:Harrison 21e Ch 397]