When Blood Glucose >600 mg/dL Without Acidosis Indicates HHNK
Blood glucose ≥600 mg/dL without acidosis should prompt immediate assessment for hyperglycemic hyperosmolar nonketotic syndrome (HHNK/HHS), which is formally diagnosed when effective serum osmolality is ≥320 mOsm/kg, arterial pH >7.30, serum bicarbonate ≥15 mEq/L, and ketones are absent or minimal. 1
Diagnostic Criteria for HHNK/HHS
The American Diabetes Association establishes specific thresholds that must all be met simultaneously:
- Plasma glucose ≥600 mg/dL (the threshold mentioned in your question) 2, 1
- Effective serum osmolality ≥320 mOsm/kg, calculated as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 3
- Arterial pH >7.30 (distinguishes from DKA) 1
- Serum bicarbonate ≥15 mEq/L 1
- Absent or minimal ketones (small by nitroprusside reaction in urine, small in serum) 1
- Altered mental status ranging from stupor to coma, which correlates with degree of hyperosmolality 1
Critical Point: Glucose Alone Is Insufficient
Simply having glucose >600 mg/dL without acidosis does NOT automatically equal HHNK—you must calculate the effective serum osmolality to confirm the diagnosis. 1 A patient could have severe hyperglycemia (>600 mg/dL) without reaching the osmolality threshold of ≥320 mOsm/kg, particularly if they are adequately hydrated or have lower sodium levels.
Essential Immediate Laboratory Workup
When you encounter glucose ≥600 mg/dL without acidosis, obtain immediately: 1
- Arterial blood gases
- Complete metabolic panel (to calculate osmolality)
- Serum and urine ketones
- Complete blood count with differential
- Electrocardiogram
- Cultures (blood, urine, throat) if infection suspected
Calculate Corrected Sodium
A critical pitfall is using uncorrected sodium values—hyperglycemia causes pseudohyponatremia. 1, 3 Add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose above 100 mg/dL to determine true sodium status. 1, 3 This corrected value is essential for accurate osmolality calculation.
Key Distinctions from DKA
HHNK differs fundamentally from DKA in several ways: 1
- Evolution: Develops over days to weeks (vs. hours in DKA) 1
- Dehydration: More severe (typical deficit 9 liters) 3
- Acidosis: Absent or minimal (pH >7.30) vs. significant in DKA (pH <7.30) 1
- Mental status changes: More common and severe in HHNK 1
Clinical Context Matters
HHNK typically occurs in elderly patients with type 2 diabetes, often with no prior diabetes diagnosis. 4, 5, 6 Common precipitants include infection, certain medications (diuretics, corticosteroids, beta-blockers, phenytoin), and inadequate fluid intake. 4 The mortality rate remains 10-20% even with treatment, making prompt recognition critical. 6
Practical Algorithm
When glucose >600 mg/dL without acidosis:
- Immediately calculate effective osmolality using the formula above 1
- If osmolality ≥320 mOsm/kg: Diagnose HHNK and initiate aggressive treatment 1
- If osmolality <320 mOsm/kg: Severe hyperglycemia requiring treatment but not meeting HHNK criteria
- Check for altered mental status—its presence strengthens the diagnosis 1
- Assess for precipitating factors (infection most common) 4
Warning Signs
Hypothermia, if present despite infection, is a poor prognostic sign. 1 Patients may be normothermic or hypothermic due to peripheral vasodilation despite having an infectious precipitant. 1