A 62-year-old man with type 2 diabetes mellitus is brought to hospital with altered mental status, severe dehydration, and a capillary blood glucose of 680 mg/dL. Vital signs show tachycardia (HR 118/min) and hypotension (BP 90/58 mmHg). Serum osmolality is measured at 335 mOsm/kg. Which investigation is most specific for differentiating hyperglycemic hyperosmolar state (HHS) from diabetic ketoacidosis in this clinical context?

Explanation

## Differentiating HHS from DKA: The Role of Ketone Assessment **Key Point:** HHS and DKA both present with severe hyperglycemia and hyperosmolality, but HHS is characterized by **absent or minimal ketonemia**, whereas DKA shows **marked ketonemia and ketonuria**. Serum β-hydroxybutyrate is the most specific differentiator. **High-Yield:** In HHS, residual insulin secretion (though inadequate for glucose control) is sufficient to suppress lipolysis and ketone production. In DKA, absolute or relative insulin deficiency allows unchecked lipolysis and ketogenesis. This is the pathophysiologic distinction that guides management. ### Comparison: HHS vs. DKA | Feature | DKA | HHS | |---------|-----|-----| | **Serum β-hydroxybutyrate** | **Markedly elevated (> 3 mmol/L)** | **Absent or minimal (< 1 mmol/L)** | | **Arterial pH** | < 7.35 (acidemia) | ≥ 7.30 (normal or mild alkalemia) | | **HCO₃⁻** | < 18 mEq/L | ≥ 18 mEq/L | | **Serum osmolality** | < 320 mOsm/kg | **> 320 mOsm/kg** | | **Glucose** | 250–800 mg/dL | 600–1200 mg/dL | | **Anion gap** | Elevated (> 12) | Normal or mildly elevated | | **Altered mental status** | Mild–moderate | Often severe | **Clinical Pearl:** A patient with glucose 680, osmolality 335, and **negative serum ketones** has HHS until proven otherwise. The absence of ketonemia despite severe hyperglycemia is pathognomonic for HHS. **Mnemonic — HHS vs. DKA: "K" for Ketones** - **DKA = K**etones **present** (K is in DKA) - **HHS = K**etones **absent** (no K in HHS) ### Why Serum β-Hydroxybutyrate? β-hydroxybutyrate is the predominant ketone body in blood (80% of total ketones) and is more specific than: - Urine ketones (can persist for hours after serum ketones clear) - Serum acetoacetate (minor component; can be falsely low in severe acidosis) - Nitroprusside test (detects acetoacetate and acetone, not β-hydroxybutyrate) [cite:Harrison 21e Ch 396]