What are the main differences in clinical presentation, laboratory findings, and management between hyperosmolar hyperglycemic state (HHS) in older adults with type 2 diabetes and diabetic ketoacidosis (DKA) in younger patients with type 1 diabetes?

Differences Between HHS and DKA

HHS occurs predominantly in older adults with type 2 diabetes and presents with extreme hyperglycemia (≥600 mg/dL) and severe hyperosmolarity (≥320 mOsm/kg) without significant ketoacidosis, while DKA occurs mainly in younger patients with type 1 diabetes and features moderate hyperglycemia (≥250 mg/dL) with profound ketoacidosis (pH <7.3, bicarbonate <15 mEq/L). 1

Clinical Presentation

Patient Demographics and Onset

• HHS develops over days to weeks in older adults with type 2 diabetes, often triggered by infection, stroke, or myocardial infarction 2, 3
• DKA develops over hours to days in younger patients with type 1 diabetes, frequently precipitated by insulin omission, infection, or as the first presentation of diabetes 1, 4, 3
• Up to one-third of patients may present with mixed features of both conditions 5

Mental Status

• HHS presents with profound alterations in consciousness—stupor or coma is typical, correlating directly with the severity of hyperosmolarity 1, 2
• DKA patients range from fully alert to lethargic, with mental status changes more pronounced only in severe cases (pH <7.00) 1, 6
• The degree of mental obtundation in HHS is significantly more severe than in DKA due to extreme hyperosmolarity 2, 7

Physical Examination Findings

• HHS shows severe dehydration with poor skin turgor, tachycardia, and hypotension due to massive fluid losses (average 9 liters total body water deficit) 1, 2
• DKA demonstrates moderate dehydration (average 6 liters total body water deficit), Kussmaul respirations (deep, rapid breathing), and fruity breath odor from acetone 1
• Hypothermia in either condition is a poor prognostic sign 1

Laboratory Findings

Glucose and Osmolality

• HHS: Plasma glucose ≥600 mg/dL, effective serum osmolality ≥320 mOsm/kg (calculated as: 2[measured Na] + glucose/18) 1, 2
• DKA: Plasma glucose ≥250 mg/dL, osmolality typically <320 mOsm/kg 1

Acid-Base Status

• HHS: Arterial pH ≥7.30, serum bicarbonate ≥15 mEq/L, minimal or absent ketones 1, 2
• DKA: Arterial pH <7.30, serum bicarbonate <15 mEq/L, moderate to large ketones in blood and urine 1
• The absence of significant ketoacidosis in HHS despite severe hyperglycemia remains incompletely understood pathophysiologically 8

Electrolyte Deficits

• HHS: Sodium 100-200 mEq/kg, potassium 5-15 mEq/kg, chloride 5-13 mEq/kg 1
• DKA: Sodium ~100 mEq/kg, potassium 3-5 mEq/kg, chloride 7-10 mEq/kg 1
• Corrected serum sodium must be calculated by adding 1.6 mEq/L for each 100 mg/dL glucose elevation above 100 mg/dL 1, 2

Initial Laboratory Evaluation

Both conditions require: plasma glucose, serum electrolytes with calculated anion gap, serum osmolality, BUN/creatinine, serum ketones (β-hydroxybutyrate preferred over nitroprusside), arterial blood gases, complete blood count with differential, urinalysis with urine ketones, electrocardiogram, and HbA1c 1, 2

Management Differences

Fluid Resuscitation Priority

• HHS: Aggressive fluid replacement is the cornerstone of therapy—isotonic saline (0.9% NaCl) at 15-20 mL/kg/h in the first hour, with goal to correct 9-liter deficit within 24 hours 1, 2, 5
• DKA: Fluid replacement is important but insulin therapy is the cornerstone—same initial rate of 15-20 mL/kg/h but correcting a smaller 6-liter deficit 1, 5
• In HHS, osmolality reduction must not exceed 3-8 mOsm/kg/h to prevent cerebral edema and central pontine myelinolysis 2

Insulin Therapy Timing

• HHS: Withhold insulin until blood glucose stops falling with IV fluids alone (unless ketonemia is present), then start with 0.1 unit/kg bolus followed by 0.1 unit/kg/h infusion 2
• DKA: Begin insulin immediately after initial fluid resuscitation—0.1 unit/kg bolus followed by 0.1 unit/kg/h continuous infusion 1
• Target glucose reduction is 50-75 mg/dL/h for both conditions 2

Dextrose Addition

• HHS: Add 5% dextrose to 0.45% saline when glucose reaches 250-300 mg/dL, reducing insulin to 0.05-0.1 unit/kg/h to maintain glucose at this level until hyperosmolarity and mental status improve 2
• DKA: Add dextrose when glucose reaches 200-250 mg/dL while continuing insulin to clear ketones 1

Potassium Management

• HHS: Total body potassium deficit is 5-15 mEq/kg—add 20-30 mEq/L (2/3 KCl, 1/3 KPO₄) once renal function confirmed and K ≥3.3 mEq/L 1, 2
• DKA: Total body potassium deficit is 3-5 mEq/kg—same replacement strategy but smaller total deficit 1
• If serum potassium <3.3 mEq/L in either condition, hold insulin and give potassium replacement until K ≥3.3 mEq/L 2

Bicarbonate Use

• HHS: Not recommended, as pH is typically ≥7.30 with no prospective evidence supporting its use 2
• DKA: Generally not recommended; studies show no difference in resolution of acidosis or time to discharge 1

Prognosis and Complications

Mortality Rates

• HHS: Mortality ~15%, significantly higher than DKA, with worse outcomes in extremes of age, presence of coma, and hypotension 1, 6, 2
• DKA: Mortality <1% in children and adults when managed in experienced centers 1, 7
• Age >60 years, severity of dehydration, and presence of comorbidities determine prognosis in both conditions 7

Specific Complications

• HHS: Myocardial infarction, stroke, thrombotic events (due to hyperviscosity), central pontine myelinolysis (if osmolality corrected too rapidly), and cerebral edema (70% mortality once clinical symptoms develop beyond lethargy) 2, 8
• DKA: Cerebral edema (particularly in children with rapid correction), hyperchloremic metabolic acidosis from excessive saline, and rebound hyperglycemia if IV insulin stopped without subcutaneous overlap 2

Care Setting

Both conditions require ICU admission, but HHS demands immediate intensive care due to greater volume depletion, typical triggering by acute serious illness, and higher mortality risk 2, 5