How is hyperosmolar hyperglycemic coma diagnosed in an older adult with type 2 diabetes presenting with sudden altered mental status?

Diagnosis of Hyperosmolar Hyperglycemic State (HHS)

Diagnose HHS when plasma glucose is ≥600 mg/dL, effective serum osmolality is ≥320 mOsm/kg, arterial pH is ≥7.30, serum bicarbonate is ≥15 mEq/L, and ketones are small or absent, typically in an older adult with type 2 diabetes presenting with altered mental status and severe dehydration. 1, 2

Core Diagnostic Criteria

The American Diabetes Association establishes five mandatory metabolic thresholds that must be met simultaneously for HHS diagnosis 1, 2:

• Plasma glucose ≥600 mg/dL – This severe hyperglycemia distinguishes HHS from diabetic ketoacidosis (DKA), where glucose is typically >250 mg/dL 1, 2
• Effective serum osmolality ≥320 mOsm/kg – Calculate as: 2[measured Na (mEq/L)] + glucose (mg/dL)/18 1, 2
• Arterial pH ≥7.30 – This differentiates HHS from DKA, which has pH <7.30 1, 2
• Serum bicarbonate ≥15 mEq/L – Again distinguishing from DKA where bicarbonate is <15 mEq/L 1, 2
• Small or absent ketones in both urine and serum (ketonemia ≤3.0 mmol/L) – This is critical; significant ketonemia suggests DKA or mixed DKA/HHS 1, 2, 3

A critical nuance: Altered mental status is extremely common in HHS and correlates with the degree of hyperosmolarity, but it is not mandatory for diagnosis when metabolic criteria are met 2. Patients meeting the above thresholds warrant HHS management even if fully alert 2.

Essential Initial Laboratory Evaluation

Order the following tests immediately upon suspicion 1, 2:

• Plasma glucose – to confirm hyperglycemia ≥600 mg/dL 2
• Serum electrolytes with calculated anion gap – to assess metabolic status and rule out concurrent DKA 1, 2
• Serum osmolality (or calculate effective osmolality) – must be ≥320 mOsm/kg 1, 2
• Blood urea nitrogen and creatinine – to evaluate renal function and severity of dehydration 1, 2
• Serum ketones (preferably β-hydroxybutyrate, not nitroprusside method) – to confirm minimal ketosis 2
• Arterial blood gases – to document pH ≥7.30 1
• Complete blood count with differential – to assess for infection and hemoconcentration 1, 2
• Urinalysis with urine ketones by dipstick – should show small or absent ketones 1
• Electrocardiogram – to evaluate for myocardial infarction as precipitant 1, 2
• HbA1c – to distinguish acute decompensation from chronic poor control 2

Calculate Corrected Sodium

Always correct serum sodium for hyperglycemia by adding 1.6 mEq/L to measured sodium for each 100 mg/dL glucose elevation above 100 mg/dL 2. This corrected value is essential for accurate osmolality calculation and guides fluid management 2.

Identify Precipitating Factors

Infection is the most common trigger, but systematically evaluate for 1, 2:

• Infection (pneumonia, urinary tract infection, sepsis) – obtain bacterial cultures of blood, urine, and throat if suspected 1, 2
• Acute cerebrovascular accident or stroke – common in elderly patients 1, 2
• Myocardial infarction – check troponin and ECG 1, 2
• Medications affecting carbohydrate metabolism – corticosteroids, thiazide diuretics, SGLT2 inhibitors, sympathomimetic agents (dobutamine, terbutaline) 1, 2
• Non-compliance with diabetes medications or newly diagnosed diabetes 1
• Pancreatitis, trauma, alcohol abuse 1

Order chest X-ray if pneumonia is suspected based on clinical presentation 2.

Clinical Presentation Supporting Diagnosis

HHS evolves over days to weeks, unlike DKA which develops over hours to days 1, 2. Look for:

• Severe dehydration – poor skin turgor, dry mucous membranes, tachycardia, hypotension 1, 3
• Polyuria, polydipsia, weight loss – typically precede mental status changes by days 1, 2
• Altered mental status ranging from lethargy to stupor/coma – correlates with degree of hyperosmolarity and is more frequent in HHS than DKA 1, 4, 5
• Absence of Kussmaul respirations – distinguishes from DKA 1
• Normothermia or hypothermia despite infection – hypothermia is a poor prognostic sign 1

Critical Differential Diagnoses to Exclude

Distinguish HHS from DKA using pH, bicarbonate, and ketone levels 1, 2:

• DKA: pH <7.30, bicarbonate <15 mEq/L, significant ketones, glucose typically 250-600 mg/dL 1, 2
• HHS: pH ≥7.30, bicarbonate ≥15 mEq/L, minimal ketones, glucose ≥600 mg/dL 1, 2

Mixed DKA/HHS can occur and requires treatment addressing both conditions 3.

Starvation ketosis shows mildly elevated glucose (rarely >250 mg/dL) and bicarbonate usually not <18 mEq/L 1, 2.

Alcoholic ketoacidosis presents with variable glucose (can be hypoglycemic to mildly elevated) and profound acidosis 1, 2.

Common Diagnostic Pitfalls

• Do not rely on mental status alone – absence of altered consciousness does not exclude HHS when metabolic criteria are met 2
• Do not use nitroprusside method for ketones – measure β-hydroxybutyrate directly for accurate assessment 2
• Do not overlook mixed presentations – up to 25% may have features of both DKA and HHS 3
• Do not miss precipitating illness – failure to identify and treat the underlying cause increases mortality 1, 2

Monitoring During Initial Assessment

Check the following every 2-4 hours during initial evaluation and treatment 2:

• Glucose, sodium, potassium, chloride
• Calculated anion gap and effective osmolality
• Blood urea nitrogen and creatinine
• Venous pH and bicarbonate

Target osmolality reduction of 3-8 mOsm/kg/h to minimize risk of cerebral edema and central pontine myelinolysis 2, 3.