What are the key differences between Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)?

Key Differences Between DKA and HHS

DKA and HHS differ fundamentally in their glucose levels, acid-base status, ketone production, time course, and mental status severity—with DKA featuring severe ketoacidosis and lower glucose, while HHS presents with extreme hyperglycemia, hyperosmolality, and minimal ketosis.

Biochemical Distinctions

Glucose Levels

• DKA: Plasma glucose typically >250 mg/dL 1
• HHS: Plasma glucose markedly elevated at >600 mg/dL 1

Acid-Base Status

• DKA: Arterial pH ranges from <7.0 to 7.30 depending on severity, with serum bicarbonate ≤18 mEq/L 1
• HHS: Arterial pH >7.30 with serum bicarbonate >15 mEq/L, indicating minimal to no acidosis 1

Ketone Production

• DKA: Strongly positive urine and serum ketones due to unregulated lipolysis and ketogenesis from severe insulin deficiency 1
• HHS: Small or negative ketones—residual insulin is adequate to prevent lipolysis and ketogenesis but insufficient to control hyperglycemia 1

Osmolality

• DKA: Variable effective serum osmolality 1
• HHS: Markedly elevated effective serum osmolality >320 mOsm/kg, driving the severe hyperosmolar state 1

Anion Gap

• DKA: Elevated anion gap (>10-12 mEq/L) due to accumulation of ketoacids 1
• HHS: Variable anion gap, typically not significantly elevated 1

Clinical Presentation Differences

Time Course of Onset

• DKA: Evolves rapidly, typically within 24 hours, allowing for acute presentation with minimal warning 1
• HHS: Develops insidiously over several days to weeks, reflecting the slower progression of severe dehydration 1

Mental Status Alterations

• DKA: Patients range from alert to drowsy, with stupor/coma only in severe cases 1
• HHS: Stupor and coma are much more frequent, correlating with the degree of hyperosmolality 1

Respiratory Pattern

• DKA: Kussmaul respirations (deep, rapid breathing) are characteristic, representing respiratory compensation for metabolic acidosis 1
• HHS: Kussmaul respirations are absent due to lack of significant acidosis 1

Gastrointestinal Symptoms

• DKA: Abdominal pain and vomiting occur in up to 25% of patients, sometimes with coffee-ground emesis from hemorrhagic gastritis 1
• HHS: Abdominal pain is not a typical feature 1

Pathophysiologic Mechanisms

Insulin Deficiency Severity

• DKA: Absolute or near-absolute insulin deficiency combined with elevated counterregulatory hormones triggers uncontrolled lipolysis, releasing free fatty acids that undergo hepatic beta-oxidation to produce ketone bodies 2
• HHS: Residual beta-cell function provides enough insulin to suppress lipolysis and prevent ketogenesis, but remains inadequate to facilitate peripheral glucose utilization 1

Dehydration Severity

• DKA: Moderate dehydration from osmotic diuresis 1
• HHS: Profound dehydration is the hallmark, often more severe than in DKA, contributing to the higher mortality 1, 3

Mortality and Prognosis

Mortality Rates

• DKA: Mortality approximately 5% in experienced centers, with lower rates in younger patients 1
• HHS: Mortality remains significantly higher at approximately 15%, reflecting the older age of patients, greater comorbidity burden, and severity of hyperosmolality 1, 4

Prognostic Factors

• Both conditions have worse outcomes at extremes of age (>65 years), in the presence of coma, hypotension, and hypothermia 1, 4

Common Pitfalls

Overlap Syndromes

• Approximately 30% of hyperglycemic crises demonstrate features of both DKA and HHS, with mixed ketoacidosis and hyperosmolality—do not assume a patient fits neatly into one category 5

Euglycemic DKA

• SGLT2 inhibitors can cause DKA with glucose levels <250 mg/dL, potentially delaying diagnosis if clinicians rely solely on glucose thresholds 2

Hypothermia as Poor Prognostic Sign

• Despite infection being the most common precipitant, patients may be normothermic or hypothermic due to peripheral vasodilation—hypothermia indicates poor prognosis 1