Altered Mental Status is NOT Required for HHS Diagnosis
Altered mental status is common in HHS but is NOT a mandatory diagnostic criterion—HHS is diagnosed by metabolic thresholds alone (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg, pH ≥7.30, bicarbonate ≥15 mEq/L, minimal ketones), and patients meeting these criteria warrant immediate HHS management regardless of whether they are fully alert. 1
Core Diagnostic Criteria (All Metabolic)
The American Diabetes Association establishes five metabolic thresholds that define HHS, none of which include mental status 1:
- Plasma glucose ≥600 mg/dL 1
- Effective serum osmolality ≥320 mOsm/kg (calculated as 2[Na] + glucose/18) 1
- Arterial pH ≥7.30 1
- Serum bicarbonate ≥15 mEq/L 1
- Small or absent ketones (ketonemia ≤3.0 mmol/L) 1
Patients who meet these metabolic criteria have HHS and require immediate intensive care unit admission, even if completely alert. 1
Clinical Presentation vs. Diagnostic Criteria: A Critical Distinction
While altered mental status is common in HHS, it reflects typical presentation rather than mandatory diagnostic criteria 1:
- Change in cognitive state is common in HHS (more frequent than in DKA) 2
- Mental obtundation correlates with severity of hyperosmolarity 1
- Mental status can range from full alertness to profound coma 1
The 2025 American Diabetes Association guidelines explicitly state that the absence of altered mental status does not exclude HHS diagnosis when metabolic criteria are met. 1
Why This Distinction Matters Clinically
Mortality Risk
HHS carries up to 15% mortality, higher than DKA, making early recognition based on metabolic criteria—not clinical presentation—essential 1. Waiting for mental status changes before initiating treatment delays life-saving interventions 1.
Pathophysiology Timeline
HHS develops over days to a week, allowing progressive metabolic derangement before neurological symptoms emerge 2, 1. Polyuria, polydipsia, and weight loss typically precede mental status changes by days 1. An alert patient with marked hyperglycemia and hyperosmolarity is in the early-to-mid phase of HHS and requires immediate treatment 1.
Pediatric Protocols Clarify This
In pediatric HHS definitions, the criterion is "altered mental status OR severe dehydration," explicitly acknowledging that mental status change alone is not mandatory if severe dehydration (another marker of metabolic severity) is present 1.
Common Clinical Pitfall to Avoid
Do not delay HHS diagnosis or treatment in a fully alert patient who meets metabolic thresholds. 1 The most dangerous error is assuming that preserved alertness rules out HHS—this leads to delayed fluid resuscitation, worsening hyperosmolarity, and increased risk of cerebral edema when treatment is finally initiated 1.
Initial Management Regardless of Mental Status
All patients meeting metabolic criteria require 1:
- Immediate ICU admission for close monitoring 1
- Aggressive fluid resuscitation (average 9 liters deficit) within 24 hours 1
- Osmolality reduction limited to 3-8 mOsm/kg/h to prevent cerebral edema 1
- Delayed insulin until glucose stops falling with IV fluids alone (unless ketonemia present) 1
- Identification and treatment of precipitating illness (infection most common) 1
Supporting Research Evidence
Multiple case reports confirm HHS presentations with varying degrees of consciousness 3, 4, 5, 6, and a 2021 emergency medicine review explicitly states that while altered mental status is characteristic, the diagnosis rests on "elevated glucose, elevated serum osmolality, minimal or absent ketones" with neurologic abnormality being one feature among several 7.
The key clinical principle: Suspect HHS based on metabolic criteria, treat aggressively regardless of alertness, and recognize that preserved mental status early in the disease course does not reduce mortality risk if treatment is delayed. 1