A 62-year-old woman with type 2 diabetes mellitus presents with severe hyperglycemia (blood glucose 850 mg/dL), hyperosmolality (320 mOsm/kg), and altered mental status. Arterial pH is 7.32, HCO₃⁻ is 18 mEq/L, and serum ketones are negative. She is on metformin and a sulfonylurea. What is the most common precipitating cause of hyperglycemic hyperosmolar state (HHS) in this patient?

## Most Common Precipitant of HHS **Key Point:** Infection is the most common precipitating cause of HHS, just as it is in DKA. Infections account for 40–60% of HHS cases, with urinary tract infections and pneumonia being the most frequent. ### Pathophysiology of Infection-Triggered HHS Infection precipitates HHS through: 1. **Severe hyperglycemia** — counter-regulatory hormones (glucagon, catecholamines, cortisol) drive hepatic glucose output 2. **Osmotic diuresis** — extreme hyperglycemia (often >600 mg/dL) causes profound glycosuria and fluid loss 3. **Dehydration** — fluid losses exceed intake, leading to hyperosmolality and altered mental status 4. **Minimal ketosis** — residual insulin in type 2 diabetes suppresses lipolysis, preventing significant ketone production ### Comparison: DKA vs. HHS Precipitants | Precipitant | DKA (Type 1) | HHS (Type 2) | Frequency in HHS | | --- | --- | --- | --- | | **Infection** | 30–50% | 40–60% | Most common | | **Omission of insulin** | 20–30% | Rare | <5% | | **Acute illness** (MI, stroke) | 10–20% | 10–15% | Moderate | | **Medications** | 5–10% | 5–10% | Uncommon | | **Renal impairment** | Rare | 10–20% | More common in HHS | | **Dehydration** | Mild–moderate | Severe | Hallmark of HHS | **High-Yield:** Infection is the **single most common precipitant** of both DKA and HHS. Always screen aggressively for infection in both conditions. **Clinical Pearl:** In HHS, infection may be clinically occult — elderly patients with HHS often have silent UTIs or aspiration pneumonia. Fever and leukocytosis are less reliable in HHS than in DKA. ### Why HHS Differs from DKA - **Type 2 diabetes** retains some endogenous insulin, which suppresses lipolysis and prevents severe ketosis - **Older age** and **comorbidities** (renal disease, heart failure) make dehydration more severe - **Osmolality** rises to extreme levels (>320 mOsm/kg) due to prolonged hyperglycemia and fluid loss - **Mortality** is higher in HHS (5–15%) than DKA (1–5%) due to age and severity of dehydration ### Why Other Options Are Wrong **Acute coronary syndrome** — While ACS can precipitate HHS (accounts for ~10% of cases), it is far less common than infection. ACS triggers a stress response but does not account for the majority of HHS presentations. **Acute kidney injury** — Although renal impairment can worsen hyperglycemia and reduce glucose clearance, acute kidney injury is not a primary precipitant; it is more often a consequence of HHS rather than a cause. It accounts for <5% of primary precipitants. **Diabetic retinopathy progression** — Retinopathy is a chronic microvascular complication and has no role in precipitating acute HHS. This is a distractor unrelated to acute metabolic decompensation.