What are the diagnostic criteria for hyperosmolar hyperglycemic state in an adult with type 2 diabetes?

Diagnosis of Hyperosmolar Hyperglycemic State (HHS)

HHS is diagnosed when five metabolic criteria are simultaneously present: plasma glucose ≥600 mg/dL, effective serum osmolality ≥320 mOsm/kg, arterial pH ≥7.30, serum bicarbonate ≥15 mEq/L, and small or absent ketones in urine and serum. 1, 2

Core Diagnostic Thresholds

The American Diabetes Association establishes the following mandatory metabolic criteria that must all be met:

• Plasma glucose ≥600 mg/dL – This severe hyperglycemia distinguishes HHS from diabetic ketoacidosis (DKA), where glucose is typically 250-600 mg/dL 1, 2

• Effective serum osmolality ≥320 mOsm/kg – Calculate using the formula: 2 × [measured serum Na in mEq/L] + [glucose in mg/dL] ÷ 18 1, 2

• Arterial pH ≥7.30 – This differentiates HHS from DKA (pH <7.30) and indicates minimal acidosis 1, 2

• Serum bicarbonate ≥15 mEq/L – Reflects the absence of significant metabolic acidosis, unlike DKA where bicarbonate is <15 mEq/L 1, 2

• Small or absent ketones – Both urine dipstick and serum ketones should be minimal (ketonemia ≤3.0 mmol/L); significant ketonemia suggests DKA or mixed DKA/HHS 1, 2, 3

Essential Initial Laboratory Workup

Order these tests immediately upon clinical suspicion to confirm metabolic criteria and identify precipitating factors:

• Plasma glucose to verify ≥600 mg/dL 1
• Serum electrolytes with calculated anion gap 1, 2
• Blood urea nitrogen and creatinine to assess renal function and dehydration severity 1
• Arterial blood gas to document pH ≥7.30 1, 2
• Serum ketones (β-hydroxybutyrate preferred over nitroprusside method) 1
• Complete blood count with differential to detect infection and hemoconcentration 1, 2
• Urinalysis with dipstick ketones (should show small or absent) 1, 2
• Electrocardiogram to identify myocardial infarction as a precipitant 1, 2
• HbA1c to determine acute decompensation versus chronic poor control 1

If infection is suspected (the most common precipitant), obtain bacterial cultures from blood, urine, and throat 1, 2. If pneumonia is suspected, obtain chest X-ray 1.

Critical Calculation Adjustments

Corrected serum sodium must be calculated because hyperglycemia causes pseudohyponatremia:

• Add 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL 1, 2
• This correction is essential for accurate diagnosis and management 1

Typical Clinical Presentation

HHS develops over days to weeks (not hours like DKA), allowing specific signs to emerge 1, 3:

• Severe dehydration with poor skin turgor, dry mucous membranes, tachycardia, and hypotension (total body water deficit approximately 9 liters or 100-220 mL/kg) 1, 3, 4
• Polyuria, polydipsia, and weight loss that precede mental status changes by several days 1
• Altered mental status ranging from lethargy to stupor/coma, correlating with the degree of hyperosmolarity and occurring more frequently than in DKA 1, 2, 5
• Absence of Kussmaul respirations (deep, labored breathing), which helps differentiate from DKA 1
• Normothermia or hypothermia despite underlying infection; hypothermia is a poor prognostic sign 2

Key Diagnostic Pitfall

Do not rely solely on altered consciousness to diagnose HHS. Patients meeting metabolic criteria (glucose ≥600 mg/dL, osmolality ≥320 mOsm/kg) warrant HHS diagnosis and management even if fully alert 1. The absence of altered mental status does not exclude HHS when other criteria are met 1.

Differential Diagnosis

Distinguish HHS from other hyperglycemic emergencies using these laboratory cut-offs:

• DKA: pH <7.30, bicarbonate <15 mEq/L, significant ketonemia, glucose typically 250-600 mg/dL 1
• HHS: pH ≥7.30, bicarbonate ≥15 mEq/L, minimal ketonemia, glucose ≥600 mg/dL 1
• Starvation ketosis: Modest glucose elevation (rarely >250 mg/dL), bicarbonate usually ≥18 mEq/L 1
• Alcoholic ketoacidosis: Variable glucose (often normal or low) with profound metabolic acidosis 1

Common Precipitating Factors

Identifying and treating the underlying trigger is essential because untreated precipitants increase mortality (up to 15%) 1, 3, 6:

• Infections (most common) – pneumonia, urinary tract infection, sepsis 1, 4
• Acute cerebrovascular events (stroke), especially in older adults 1
• Myocardial infarction – assess troponin and ECG 1
• Medications that raise glucose: corticosteroids, thiazide diuretics, SGLT2 inhibitors, sympathomimetics 1, 4
• Non-adherence to diabetes therapy or newly diagnosed diabetes 1, 4
• Other stressors: pancreatitis, trauma, substance abuse (cocaine) 1, 4