Differences Between Hyperosmolar Hyperglycemic State (HHS) and Alcoholic Ketoacidosis (AKA)
Hyperosmolar Hyperglycemic State (HHS) and Alcoholic Ketoacidosis (AKA) are distinct metabolic emergencies with different pathophysiology, clinical presentations, and treatment approaches, with HHS having a significantly higher mortality rate of 15% compared to AKA. 1, 2
Pathophysiology
HHS
- Caused by relative insulin deficiency - enough insulin to prevent ketogenesis but insufficient to promote glucose utilization
- Marked hyperglycemia (typically ≥30 mmol/L or >600 mg/dL)
- Extreme hyperosmolality (≥320 mOsm/kg)
- Minimal to no ketosis (residual insulin prevents significant lipolysis)
- No significant acidosis (pH >7.3, bicarbonate ≥15 mmol/L)
- Usually occurs in patients with type 2 diabetes (known or undiagnosed)
- Develops gradually over days to weeks 1, 3, 4
AKA
- Characterized by hyperketonemia without significant hyperglycemia
- Blood glucose levels are typically normal or only mildly elevated
- Absence of glycosuria
- Significant metabolic acidosis
- Occurs in patients with history of chronic alcohol abuse
- Typically develops after a period of heavy alcohol consumption followed by reduced food intake 2, 5
Laboratory Findings
HHS
- Extreme hyperglycemia (>600 mg/dL)
- Serum osmolality >320 mOsm/kg
- Minimal or absent ketones
- Mild or no acidosis (pH >7.3)
- Bicarbonate ≥15 mmol/L
- Profound dehydration (fluid losses 100-220 ml/kg) 1, 3, 4
AKA
- Normal or mildly elevated blood glucose
- Significant ketosis (elevated β-hydroxybutyrate and acetoacetate)
- Metabolic acidosis (lower arterial pH compared to HHS)
- Lower acetoacetic acid levels compared to DKA
- Higher serum lactate levels compared to DKA
- More negative base excess compared to HHS 2, 5
Clinical Presentation
HHS
- Develops slowly over days to weeks
- Severe dehydration
- Altered mental status progressing to coma (more frequent than in DKA)
- Absence of Kussmaul respirations (no significant acidosis)
- More common in elderly patients with type 2 diabetes
- Often precipitated by infections, cerebrovascular accidents, or medications 1, 6
AKA
- History of chronic alcohol abuse
- Recent episode of heavy drinking followed by reduced food intake
- Nausea, vomiting, abdominal pain
- Altered mental status
- Signs of dehydration
- May have evidence of liver dysfunction 2, 5
Treatment Approach
HHS
- Aggressive fluid resuscitation with 0.9% sodium chloride (primary intervention)
- Fixed rate intravenous insulin infusion (started once osmolality stops falling with fluid replacement alone)
- Careful monitoring of electrolytes, particularly potassium
- Glucose infusion when blood glucose falls below 14 mmol/L
- Gradual correction of osmolality (3.0-8.0 mOsm/kg/h) to prevent neurological complications
- Target blood glucose 10-15 mmol/L in first 24 hours 1, 3, 4
AKA
- Intravenous administration of dextrose in water
- Fluid resuscitation
- Sodium bicarbonate if severe acidosis
- Insulin administration usually not necessary
- Treatment of underlying alcohol withdrawal if present
- Thiamine supplementation to prevent Wernicke's encephalopathy 2, 5
Resolution Criteria
HHS
- Osmolality <300 mOsm/kg
- Correction of hypovolemia (urine output ≥0.5 ml/kg/h)
- Return of cognitive status to pre-morbid state
- Blood glucose <15 mmol/L 3
AKA
- Resolution of acidosis
- Normalization of ketone levels
- Improvement in clinical status 2
Common Pitfalls
- Misdiagnosing AKA as DKA due to presence of ketosis and acidosis
- Failing to recognize mixed DKA/HHS states
- Administering insulin unnecessarily in AKA
- Not identifying and treating the underlying precipitating factors
- Too rapid correction of osmolality in HHS, which can lead to cerebral edema
- Overlooking alcohol withdrawal in AKA patients 7, 5
Understanding these key differences is crucial for proper diagnosis and management, as treatment approaches differ significantly between these two metabolic emergencies.