What is the differential diagnosis for a patient with altered sensorium (changed mental status), respiratory distress, and a known history of Diabetes Mellitus (DM) and Hypertension (HTN)?

Differential Diagnosis for Altered Sensorium in a Patient with Diabetes Mellitus, Hypertension, and Respiratory Distress

In a patient with diabetes, hypertension, and presenting with altered sensorium plus respiratory distress, you must immediately consider diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) as the primary diagnoses, while simultaneously evaluating for hypoglycemia, infection (particularly pneumonia or sepsis), acute coronary syndrome, stroke, and acute kidney injury. 1, 2

Immediate Life-Threatening Causes to Rule Out First

Hypoglycemia

• Check capillary blood glucose immediately - this is the fastest reversible cause of altered mental status in diabetics 1
• Blood glucose <60 mg/dL defines hypoglycemia; severe hypoglycemia causes confusion, combativeness, somnolence, seizures, or coma 1
• Hypoglycemia can mimic intoxication or withdrawal and requires immediate glucose administration 1
• Treat with 15-20g oral glucose if conscious, or glucagon/IV dextrose if unconscious 1, 3

Diabetic Ketoacidosis (DKA)

• Diagnostic criteria: blood glucose >250 mg/dL, venous pH <7.3, serum bicarbonate <15 mEq/L, and moderate ketonuria/ketonemia 2
• DKA can present with altered sensorium ranging from drowsiness to coma, particularly in severe cases (pH <7.00) 2
• Respiratory distress manifests as Kussmaul breathing (deep, rapid respirations) attempting to compensate for metabolic acidosis 2
• Obtain immediate labs: complete metabolic panel, venous blood gas, CBC, urinalysis, serum ketones (β-hydroxybutyrate preferred over urine ketones) 2
• Calculate anion gap: [Na+] - ([Cl-] + [HCO3-]); should be >10-12 mEq/L in DKA 2

Hyperosmolar Hyperglycemic State (HHS)

• Characterized by severe hyperglycemia (often >600 mg/dL), hyperosmolality (>320 mOsm/kg), severe dehydration, and altered consciousness WITHOUT significant ketoacidosis 1, 4
• More common in type 2 diabetes; mortality remains high 4
• Altered sensorium is frequent and can range from confusion to coma 4
• Serum osmolality >320 mOsm/kg with minimal ketones distinguishes HHS from DKA 4
• Hypernatremia may occur (unlike typical hyponatremia in DKA), requiring careful fluid management 5

Infection-Related Causes

Pneumonia/Respiratory Infection

• Respiratory distress with altered mental status suggests severe pneumonia or sepsis 1, 4
• Infection is a common precipitant of both DKA and HHS 1, 4
• Obtain chest X-ray, blood cultures, urine cultures if infection suspected 2
• Diabetics have increased susceptibility to infections 1

Sepsis

• Can cause altered mental status through hypoperfusion and metabolic derangements 4
• May precipitate DKA/HHS or acute kidney injury 4
• Look for fever, tachycardia, hypotension, elevated white blood cell count 4

Cardiovascular Causes

Acute Coronary Syndrome/Myocardial Infarction

• Diabetics may have atypical presentations without classic chest pain 1
• Respiratory distress may indicate acute heart failure or pulmonary edema 1
• Check troponin, ECG; altered mental status can occur with cardiogenic shock 1
• Type 2 MI (supply-demand mismatch) occurs with severe illness, hypotension, or respiratory failure 1

Hypertensive Emergency

• Severe hypertension can cause hypertensive encephalopathy with altered mental status 6, 7
• Check blood pressure immediately; look for end-organ damage 6
• Diabetics have increased prevalence of hypertension and accelerated vascular complications 8

Neurological Causes

Stroke (Ischemic or Hemorrhagic)

• Diabetics have increased stroke risk 1, 4
• Altered mental status with focal neurological signs suggests stroke 1
• HHS itself can cause stroke-like symptoms or precipitate actual cerebrovascular events 4
• Consider head CT if first episode of altered mental status, focal signs, or inadequate response to treatment 1

Hepatic Encephalopathy

• If patient has underlying cirrhosis, hepatic encephalopathy is a diagnosis of exclusion 1
• Other causes must be ruled out: DKA, HHS, electrolyte disorders, intracranial bleeding, infections 1
• Grade 3-4 hepatic encephalopathy presents with severe confusion to coma 1

Metabolic/Electrolyte Causes

Acute Kidney Injury with Uremia

• Diabetic nephropathy increases risk; check BUN, creatinine 1, 2
• Uremia causes altered mental status and can worsen with dehydration 4
• Prerenal azotemia common in HHS due to severe dehydration 4

Electrolyte Imbalances

• Hyponatremia or hypernatremia (particularly with HHS) 1, 5
• Hypokalemia or hyperkalemia (common in DKA) 2
• Hypercalcemia, hypomagnesemia 1

Drug-Related Causes

Medication Effects

• Insulin overdose causing hypoglycemia 3
• Sedatives, opioids, or other CNS depressants 1
• Alcohol intoxication or withdrawal 1

Systematic Diagnostic Approach

Step 1: Immediate bedside assessment (within 5 minutes)

• Capillary blood glucose 1
• Vital signs including oxygen saturation 1
• Brief neurological exam for focal deficits 1

Step 2: Stat laboratory evaluation

• Complete metabolic panel (glucose, electrolytes, BUN, creatinine, bicarbonate) 2
• Venous blood gas (pH, bicarbonate) 2
• Serum β-hydroxybutyrate or urine ketones 2
• Calculate corrected sodium: [measured Na] + [(glucose - 100)/100] × 1.6 2
• Calculate serum osmolality: 2[Na] + [glucose/18] + [BUN/2.8] 2
• Calculate anion gap 2
• CBC with differential 2
• Troponin and ECG 1

Step 3: Imaging and cultures as indicated

• Chest X-ray if respiratory distress present 2
• Blood and urine cultures if infection suspected 2
• Head CT if: first episode, focal signs, seizures, or inadequate response to treatment 1

Step 4: Severity classification if DKA confirmed

• Mild: pH 7.25-7.30, bicarbonate 15-18 mEq/L, alert 2
• Moderate: pH 7.00-7.24, bicarbonate 10-15 mEq/L, drowsy 2
• Severe: pH <7.00, bicarbonate <10 mEq/L, stuporous/comatose 2

Critical Pitfalls to Avoid

• Do not assume altered mental status is solely from hyperglycemia - always check for hypoglycemia first, as it is immediately reversible 1
• Do not rely on urine ketones alone - they measure acetoacetate, not β-hydroxybutyrate, and can be falsely negative or misleading 2
• Do not miss mixed DKA/HHS presentations - patients can have features of both 1
• Do not overlook infection as precipitant - always obtain cultures before antibiotics if infection suspected 2
• Do not forget to correct sodium for hyperglycemia - true sodium status affects fluid management 2
• Do not delay head imaging if atypical features present - stroke can coexist with or mimic metabolic causes 1, 4
• Do not assume hepatic encephalopathy without excluding other causes - DKA, HHS, and infections must be ruled out first 1