Differentiating DKA from HHS
DKA and HHS are differentiated primarily by three key laboratory values: blood glucose level, pH/bicarbonate, and the presence or absence of ketones.
Diagnostic Criteria
DKA Criteria 12:
- Blood glucose ≥250 mg/dL
- Venous pH <7.3
- Bicarbonate <15 mEq/L
- Moderate to severe ketonuria or ketonemia
HHS Criteria 1:
- Blood glucose ≥600 mg/dL (significantly higher than DKA)
- Venous pH ≥7.3 (no significant acidosis)
- Bicarbonate ≥15 mEq/L
- Minimal or absent ketones
- Altered mental status or severe dehydration
Key Distinguishing Features
The Critical Differences:
Glucose threshold: HHS presents with much more severe hyperglycemia (≥600 mg/dL vs ≥250 mg/dL). This is the most immediately apparent difference on initial labs 1.
Ketosis and acidosis: DKA is characterized by significant ketone production and metabolic acidosis, while HHS has minimal to no ketones and preserved pH 11. The pathophysiologic explanation is that HHS patients retain enough residual insulin (C-peptide) to prevent lipolysis and ketogenesis, but not enough to control glucose 11.
Time course: HHS typically evolves over days to weeks, whereas DKA develops more rapidly, often within 24 hours 1.
Mental status: While both can present with altered consciousness, profound mental status changes and coma are more characteristic of HHS due to extreme hyperosmolarity 1.
Clinical Presentation Patterns
DKA typically presents with:
- Kussmaul respirations (deep, rapid breathing)
- Fruity breath odor (acetone)
- Abdominal pain and vomiting
- Younger patients, more common in type 1 diabetes 13
HHS typically presents with:
- Profound dehydration
- Neurological symptoms (confusion, lethargy, focal deficits)
- Older patients, more common in type 2 diabetes 14
Important Caveats
Mixed presentations occur: Approximately one-third of cases show overlapping features with both ketoacidosis and hyperosmolarity present 45. Don't rely solely on glucose thresholds—always check pH, bicarbonate, and ketones 5.
Mortality differences: HHS carries a significantly higher mortality rate (15%) compared to DKA (5%), largely due to older patient age, comorbidities, and delayed presentation 113.
Ketone measurement: Use β-hydroxybutyrate (β-OHB) blood measurement rather than nitroprusside urine testing, as the latter only detects acetoacetate and acetone, not the predominant ketone body in DKA 1. During treatment, β-OHB converts to acetoacetate, which can falsely suggest worsening ketosis on urine testing.
Practical Laboratory Algorithm
- Check blood glucose immediately: >600 mg/dL suggests HHS
- Obtain venous pH and bicarbonate: pH <7.3 and HCO₃ <15 mEq/L indicates DKA
- Measure serum or urine ketones: Significant ketonemia/ketonuria confirms DKA
- Calculate serum osmolality: Severe hyperosmolarity (>320 mOsm/kg) supports HHS 6
- Assess anion gap: Elevated in DKA due to ketoacids 2
The diagnosis is not mutually exclusive—treat based on the dominant metabolic derangement present, recognizing that management principles overlap significantly between the two conditions 17.