What is the clinical basis for diagnosing Hyperosmolar Hyperglycemic State (HHS) versus Diabetic Ketoacidosis (DKA)?

Clinical Basis for Diagnosing Hyperosmolar Hyperglycemic State (HHS) versus Diabetic Ketoacidosis (DKA)

The key diagnostic difference between HHS and DKA is that HHS presents with plasma glucose >600 mg/dL, minimal or absent ketosis, arterial pH >7.30, and effective serum osmolality >320 mOsm/kg, while DKA presents with glucose >250 mg/dL, significant ketosis, arterial pH <7.30, and bicarbonate <18 mEq/L. 1

Laboratory Criteria

DKA Diagnostic Criteria

• Plasma glucose >250 mg/dL 2, 1
• Arterial pH ranging from <7.00 to 7.30 1
• Serum bicarbonate <10 to 18 mEq/L 1
• Positive serum and urine ketones 1
• Anion gap >10-12 mEq/L 1

HHS Diagnostic Criteria

• Markedly elevated plasma glucose, usually >600 mg/dL 2, 1
• Arterial pH typically >7.30 1
• Serum bicarbonate typically >15 mEq/L 1
• Small or absent ketones in serum and urine 1
• Effective serum osmolality >320 mOsm/kg, calculated as 2[measured Na+ (mEq/L)] + glucose (mg/dL)/18 1
• Variable anion gap 1

Clinical Presentation Differences

Time Course

• DKA typically develops rapidly within 24 hours 2, 1
• HHS evolves more slowly over several days to weeks 2, 1

Symptoms

• Both conditions present with polyuria, polydipsia, polyphagia, weight loss, dehydration, and weakness 2
• DKA often includes abdominal pain and vomiting (25% of cases may have coffee-ground emesis) 2, 1
• HHS has less common abdominal pain but more profound dehydration 1

Physical Findings

• DKA: Kussmaul respirations, poor skin turgor, tachycardia, hypotension 2
• HHS: More severe dehydration, higher likelihood of altered mental status and coma 2, 1
• Mental status in DKA ranges from alert to stupor/coma, while HHS more frequently presents with stupor/coma 1

Pathophysiological Differences

• Both conditions involve reduced effective insulin action with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) 2
• DKA is characterized by significant insulin deficiency leading to unregulated lipolysis and ketogenesis 2, 1
• HHS has residual insulin action sufficient to prevent significant ketogenesis but inadequate to control hyperglycemia 1

Common Pitfalls to Avoid

• Failing to identify mixed DKA/HHS states, which can occur and require elements of both treatment approaches 3
• Initiating insulin too early in HHS before adequate fluid resuscitation, which may worsen outcomes 4, 5
• Not recognizing that fluid replacement alone will cause a fall in blood glucose in HHS 4
• Failing to identify and treat the precipitating cause (most commonly infection) 1
• Reducing osmolality too rapidly, which may lead to cerebral edema or central pontine myelinolysis 4, 6

Management Considerations Based on Diagnosis

• Initial fluid therapy for both conditions involves isotonic saline (0.9% NaCl) at 15-20 mL/kg/hr during the first hour 1
• HHS generally requires more aggressive fluid replacement (100-220 ml/kg) due to more severe dehydration 1, 6
• In HHS, withhold insulin until blood glucose is no longer falling with IV fluids alone (unless ketonaemic) 4, 6
• In DKA, insulin therapy should be started immediately along with fluid resuscitation 1
• Aim to reduce osmolality by 3-8 mOsm/kg/h in HHS to prevent neurological complications 4, 6
• Bicarbonate therapy may be required in severe DKA cases (pH <7.0) but is not typically needed in HHS 1

Mortality Risk

• DKA has approximately 5% mortality rate in experienced centers 1
• HHS has a higher mortality rate of approximately 15% 1
• Prognosis for both conditions is worsened by extremes of age, coma, and hypotension 2, 1