Findings in Hyperosmolar Hyperglycemic State (HHS)
HHS presents with severe hyperglycemia (≥600 mg/dL), marked hyperosmolality (≥320 mOsm/kg), profound dehydration, and altered mental status ranging from lethargy to coma, but critically lacks significant ketosis or acidosis that characterizes DKA. 1
Clinical Presentation
Timeline and Evolution
HHS evolves slowly over days to weeks, unlike DKA which develops within 24 hours 1. This insidious onset often delays recognition and contributes to the high 15% mortality rate 1.
Key Clinical Features
Neurological manifestations:
- Mental status alterations are more frequent and severe in HHS than DKA 1
- Spectrum ranges from full alertness to profound lethargy, stupor, or coma
- Coma is the expected presentation when osmolality exceeds 320 mOsm/kg 1
Dehydration signs:
- Poor skin turgor
- Tachycardia
- Hypotension or frank shock
- Profound volume depletion (fluid losses of 100-220 mL/kg) 2
Classic hyperglycemic symptoms:
- Polyuria, polydipsia, polyphagia
- Weight loss
- Weakness
Critical distinguishing features from DKA:
- Absence of Kussmaul respirations (no compensatory hyperventilation since no significant acidosis) 1
- Absence of abdominal pain (abdominal pain occurs only in DKA) 1
- Patients may be normothermic or even hypothermic despite infection; hypothermia is a poor prognostic sign 1
Laboratory Findings
Diagnostic Criteria (American Diabetes Association)
Glucose and osmolality:
- Plasma glucose ≥600 mg/dL 1
- Effective serum osmolality ≥320 mOsm/kg (calculated as: 2[Na] + glucose/18) 1
- Recent evidence suggests effective osmolality >300 mOsm/L may be more sensitive 3
Acid-base status:
Ketone status:
- Urine ketones: small or negative 1
- Serum ketones: small or negative 1
- This distinguishes HHS from DKA where ketones are strongly positive
Anion gap:
- Variable (may be normal or mildly elevated) 1
- Contrasts with DKA where anion gap is consistently >10-12 mEq/L
Additional Laboratory Abnormalities
Electrolytes:
- Corrected sodium for hyperglycemia is critical: 95.4% of HHS patients have hypernatremia when sodium is corrected for glucose, though only 8% have elevated measured sodium 3
- Potassium losses from osmotic diuresis (despite possible normal or elevated initial levels)
- Electrolyte derangements from profound osmotic diuresis 1
Renal function:
- Elevated BUN/creatinine from prerenal azotemia
- Acute kidney injury is common 4
Other findings:
- Leukocytosis may occur even without infection
- Hemoconcentration from severe dehydration
Important Clinical Nuances
Mixed Presentations
65.5% of HHS cases have concurrent DKA features 3, challenging the traditional view that HHS and DKA are distinct entities. Recent evidence suggests significant ketonemia and acidosis should not automatically exclude HHS diagnosis 3.
Precipitating Factors to Identify
Infection is the most common trigger 1. Other precipitants include:
- Cerebrovascular accident
- Myocardial infarction
- Pancreatitis
- Medications (corticosteroids, thiazides, sympathomimetics, SGLT2 inhibitors)
- Inadequate fluid intake (especially in elderly or institutionalized patients) 1
High-Risk Populations
- Elderly patients, particularly nursing home residents 1
- 32% of HHS patients have no prior diabetes diagnosis 4
- Increasingly recognized in children and younger adults with type 2 diabetes 2, 5
Common Pitfalls
Do not rely on measured sodium alone—always calculate corrected sodium for hyperglycemia to assess true free water deficit 3.
Do not dismiss HHS if ketones are present—mixed HHS-DKA occurs in two-thirds of cases 3.
Do not overlook infection despite normal or low temperature—peripheral vasodilation can mask fever 1.
Recognize that mental status changes correlate with osmolality severity—this is a key distinguishing feature from DKA where mental status changes are less prominent 1.