What are the key differences in presentation, laboratory findings, and management between diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in a patient with severe hyperglycemia?

Differentiating DKA from HHS: Key Clinical and Laboratory Distinctions

The most critical initial test to differentiate DKA from HHS is a venous blood gas measuring pH and bicarbonate, with DKA showing pH <7.3 and bicarbonate <15 mEq/L, while HHS presents with pH >7.3 and bicarbonate >15 mEq/L. 1

Diagnostic Criteria: The Core Differences

DKA Diagnostic Features

• Glucose >250 mg/dL (though euglycemic DKA can occur in ~10% of cases) 1, 2
• Venous pH <7.3 1
• Bicarbonate <15 mEq/L (severe DKA: <10 mEq/L) 1, 3
• Anion gap >10-12 mEq/L 1
• Positive ketones (β-hydroxybutyrate preferred for measurement) 1

HHS Diagnostic Features

• Glucose >600 mg/dL (markedly higher than DKA) 1
• Venous pH >7.3 1
• Bicarbonate >15 mEq/L 1
• Effective serum osmolality >320 mOsm/kg (calculated as: 2[Na] + glucose/18) 1
• Minimal to mild ketonuria/ketonemia (key distinguishing feature) 1
• Altered mental status or severe dehydration 1

Clinical Presentation: Timeline and Symptoms

Temporal Evolution

• DKA evolves rapidly (typically within 24 hours), particularly in type 1 diabetes 4
• HHS develops slowly (over several days to weeks) 4

Physical Examination Findings

DKA-Specific Features:

• Kussmaul respirations (deep, rapid breathing) 4
• Abdominal pain (present only in DKA, not HHS) 4
• Fruity breath odor from acetone 4

Shared Features:

• Poor skin turgor indicating dehydration 4
• Tachycardia and hypotension 4
• Altered mental status (more profound in HHS) 4
• Polyuria, polydipsia, polyphagia, weight loss 4

Pathophysiologic Distinctions

The fundamental difference lies in insulin availability: DKA results from absolute insulin deficiency leading to unrestrained lipolysis and ketogenesis, while HHS has residual insulin sufficient to prevent ketone formation but inadequate to prevent severe hyperglycemia 4, 5.

• DKA: Insulin deficiency + elevated counterregulatory hormones → lipolysis → free fatty acid oxidation → ketone bodies (β-hydroxybutyrate and acetoacetate) → metabolic acidosis 4
• HHS: Residual C-peptide/insulin adequate to prevent lipolysis and ketogenesis but insufficient for glucose utilization 4

Laboratory Workup Algorithm

Initial Essential Tests:

1. Venous blood gas (most important differentiating test) 1
2. Complete metabolic panel (glucose, electrolytes, BUN, creatinine) 1
3. Serum osmolality calculation 1
4. β-hydroxybutyrate (preferred over nitroprusside-based tests) 1
5. Anion gap calculation 1
6. ECG (detect potassium-related arrhythmias) 1
7. CBC with differential and urinalysis (identify precipitating infections) 1

Management Differences

Fluid Resuscitation

Both conditions require aggressive initial fluid replacement with 0.9% NaCl at 15-20 mL/kg/h (1-1.5 L) during the first hour, though HHS typically requires more total volume replacement due to greater dehydration. 1

Insulin Therapy Timing

• DKA: Start insulin after initial fluid resuscitation at 0.1 units/kg/h (5-7 units/h in adults) 1
• HHS: Delay insulin until after initial fluid resuscitation, then use same dosing as DKA 1

This timing difference is critical—premature insulin in HHS without adequate fluid replacement can precipitate vascular collapse 6.

Potassium Replacement

• **If K+ <3.3 mEq/L:** Give 20-30 mEq/h and hold insulin until K+ >3.3 mEq/L 1
• Monitor closely as insulin drives potassium intracellularly 1

Bicarbonate Therapy

Bicarbonate is generally not recommended in either condition, as studies show no difference in resolution of acidosis or time to discharge. 1

Resolution Criteria

DKA Resolution

• Glucose <200 mg/dL 1
• Serum bicarbonate ≥18 mEq/L 1
• Venous pH >7.3 1
• Anion gap ≤12 mEq/L 1

HHS Resolution

• Normalization of mental status 1
• Normalization of osmolality 1
• Ability to tolerate oral intake 1

Mortality and Prognosis

HHS carries significantly higher mortality (15%) compared to DKA (5% in experienced centers), particularly at extremes of age and with coma or hypotension. 4, 5

Common Pitfalls to Avoid

• Premature termination of IV insulin before ketone clearance in DKA 6
• Insufficient subcutaneous insulin dosing before discontinuing IV insulin 6
• Starting insulin before adequate fluid resuscitation in HHS 1
• Missing euglycemic DKA (associated with SGLT2 inhibitors, pregnancy, alcohol use) 2
• Failing to identify and treat precipitating infections (common in both conditions) 1