What is the difference between Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) in terms of diagnosis and treatment?

DKA versus HHS: Key Differences in Diagnosis and Treatment

DKA and HHS are distinct hyperglycemic emergencies that differ fundamentally in their degree of ketoacidosis, osmolality, and speed of onset—DKA presents with severe acidosis and ketosis developing rapidly (<24 hours), while HHS presents with extreme hyperglycemia and hyperosmolarity but minimal ketosis evolving over days to weeks. 1

Diagnostic Criteria: The Critical Laboratory Distinctions

Glucose and Osmolality

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

Acid-Base Status (The Defining Difference)

• DKA: Arterial pH ranges from <7.00 (severe) to 7.25-7.30 (mild), with serum bicarbonate <10 to 15-18 mEq/L 1, 2
• HHS: Arterial pH >7.30 with serum bicarbonate >15 mEq/L 1, 2

Ketone Bodies (The Pathophysiologic Separator)

• DKA: Positive serum and urine ketones—this is the hallmark finding 1, 2
• HHS: Small or absent ketones because residual insulin is sufficient to prevent significant lipolysis and ketogenesis 2, 3

Anion Gap

• DKA: Elevated anion gap >10-12 mEq/L (calculated as Na+ - [Cl- + HCO3-]) 1, 2
• HHS: Variable anion gap 1, 2

Mental Status

• DKA: Ranges from alert to stupor/coma, but patients are more commonly alert or drowsy 1, 2
• HHS: Stupor and coma are significantly more frequent due to severe hyperosmolality 1, 2

Clinical Presentation: Recognizing the Patterns

Temporal Evolution (Critical for Early Recognition)

• DKA: Develops rapidly, typically within 24 hours, and can present acutely without warning 1, 2
• HHS: Evolves slowly over several days to weeks, allowing more profound dehydration to develop 1, 2

Shared Symptoms

Both conditions present with polyuria, polydipsia, polyphagia, weight loss, dehydration, and weakness 1

Distinguishing Clinical Features

• DKA-specific: Kussmaul respirations (deep, rapid breathing to compensate for acidosis), abdominal pain, and vomiting (occurs in up to 25% of patients, sometimes with coffee-ground emesis from hemorrhagic gastritis) 1, 2
• HHS-specific: More profound dehydration with poor skin turgor, higher likelihood of severe mental status changes including coma 1, 2

Physical Examination Findings

Both may show tachycardia, hypotension, altered mental status, and shock; hypothermia is a poor prognostic sign if present 1

Pathophysiology: Understanding the Mechanisms

Common Pathway

Both disorders result from reduced effective insulin action combined with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone), leading to increased hepatic/renal glucose production and impaired peripheral glucose utilization 1

The Critical Difference

• DKA: Severe insulin deficiency triggers lipolysis, releasing free fatty acids that undergo beta-oxidation and unregulated ketogenesis, producing ketone bodies and metabolic acidosis 1, 2, 3
• HHS: Residual beta-cell insulin secretion is adequate to prevent significant lipolysis and ketogenesis but insufficient to control hyperglycemia, resulting in extreme glucose elevation without substantial ketosis 2, 3

Mixed Presentations

Approximately one-third of patients present with overlapping features of both DKA and HHS 4

Treatment Approach: Algorithmic Management

Initial Fluid Therapy (First Priority in Both)

• Both conditions: Start with isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr during the first hour to restore intravascular volume and renal perfusion 2
• HHS requires more aggressive fluid replacement due to more severe dehydration 2
• In adults with mixed features, fluids may be administered more rapidly than in pure DKA because the risk of fatal cerebral edema is low 4

Insulin Therapy

• DKA: Insulin therapy is the cornerstone of treatment—administer intravenous insulin infusion and continue until resolution of ketonemia, not just normalization of glucose 4, 5
• HHS: Fluid replacement is the cornerstone, with insulin playing a supportive role 4
• Critical pitfall: Premature termination of IV insulin before ketones clear and insufficient timing/dosing of subcutaneous insulin before stopping IV insulin are common errors 5

Electrolyte Replacement

Potassium replacement is essential in both conditions as insulin therapy drives potassium intracellularly 2, 5

Bicarbonate Therapy

Consider only in severe DKA with pH <7.0; not typically needed in HHS 2

Identifying and Treating Precipitating Factors

The most common precipitating factor for both is infection; other causes include cerebrovascular accident, myocardial infarction, pancreatitis, trauma, medication non-compliance (especially insulin omission in DKA), and drugs affecting carbohydrate metabolism (corticosteroids, thiazides, sympathomimetics) 1, 2

Mortality and Prognosis

• DKA mortality: Approximately 5% in experienced centers 1, 2, 3
• HHS mortality: Significantly higher at approximately 15% 1, 2, 3
• Poor prognostic factors: Extremes of age (especially >65 years), presence of coma, and hypotension worsen outcomes in both conditions 1, 2, 3

Critical Pitfalls to Avoid

• Failing to identify and treat the underlying precipitating cause (most commonly infection) 2
• Stopping IV insulin before ketones have cleared in DKA 5
• Inadequate subcutaneous insulin dosing or timing before discontinuing IV insulin 5
• In younger patients with mixed features, avoid rapid correction with hypotonic fluids to prevent cerebral edema 4
• Assuming normothermia rules out infection—patients can be hypothermic due to peripheral vasodilation 1
• Underestimating fluid requirements in HHS due to the prolonged evolution and severe dehydration 2, 4