What is the differential diagnosis for a 54-year-old female with hypertension and type 2 diabetes (T2D) on insulin, presenting with tachycardia, hyperglycemia, shortness of breath, dizziness on exertion, diarrhea, migraine, polyuria, and polydipsia?

Differential Diagnosis for Hyperglycemia with Tachycardia and Systemic Symptoms in a Diabetic Patient

This patient's presentation of marked hyperglycemia with polyuria, polydipsia, tachycardia, and gastrointestinal symptoms most likely represents a hyperglycemic crisis—either diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), or a mixed presentation of both conditions. 1

Primary Differential Considerations

1. Hyperosmolar Hyperglycemic State (HHS)

• Most likely diagnosis given the patient's type 2 diabetes on insulin, age (54 years), and classic presentation 1
• Characterized by severe hyperglycemia (typically >600 mg/dL), hyperosmolality, and profound dehydration without significant ketoacidosis 1
• The triad of polyuria, polydipsia, and polyphagia reflects osmotic diuresis from severe hyperglycemia 1
• Tachycardia results from volume depletion and dehydration 1
• Dizziness on exertion indicates orthostatic hypotension from intravascular volume depletion 1
• Diarrhea may represent gastrointestinal manifestations of the metabolic derangement 1
• Patients with known diabetes who become hyperglycemic and are unable to take adequate fluids are at highest risk 1

2. Diabetic Ketoacidosis (DKA)

• Less common in type 2 diabetes but can occur, particularly in insulin-treated patients 1
• DKA seldom occurs spontaneously in type 2 diabetes but may arise with infection, missed insulin doses, or other stressors 1
• Classic symptoms include polyuria, polydipsia, and signs of dehydration 1, 2
• Gastrointestinal symptoms (nausea, vomiting, abdominal pain) are common 1, 2
• Tachypnea (compensatory for metabolic acidosis) would be expected if DKA is present 2

3. Mixed DKA/HHS Presentation

• Up to one-third of patients present with overlapping features of both conditions 3, 4
• These patients require tailored therapy addressing both ketoacidosis and severe hyperosmolarity 3
• The therapeutic approach remains similar: fluid administration, intravenous insulin, and electrolyte replacement 3

Secondary Differential Considerations

4. Precipitating Infection

• Infection is the most common precipitating factor for both DKA and HHS 1
• Patients can be normothermic or hypothermic despite infection due to peripheral vasodilation 1
• Consider urinary tract infection, pneumonia, or other occult infections 2
• Obtain bacterial cultures of urine, blood, and throat if infection is suspected 1

5. Medication-Induced Hyperglycemia

• Corticosteroids, thiazides, and sympathomimetic agents can precipitate hyperglycemic crises 1
• Review the patient's medication list for drugs affecting carbohydrate metabolism 1

6. Acute Coronary Syndrome or Myocardial Infarction

• Tachycardia and shortness of breath may indicate cardiac ischemia 1
• Stress from myocardial infarction can precipitate DKA or HHS 1
• Obtain electrocardiogram as part of initial evaluation 1

7. Cerebrovascular Event

• Stroke can precipitate hyperglycemic crisis and present with altered mental status 1
• Consider if neurological symptoms are prominent beyond expected metabolic derangement 1

Critical Diagnostic Pitfalls to Avoid

Laboratory Evaluation Required

• Immediate testing must include: plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes with calculated anion gap, serum osmolality, urinalysis with urine ketones, arterial blood gases, complete blood count, and electrocardiogram 1
• Calculate effective osmolality: 2[Na] + glucose/18 (normal <295 mOsm/L; HHS typically >320 mOsm/L) 1
• Measure serum ketones (β-hydroxybutyrate preferred over urine ketones) to distinguish DKA from HHS 1

Key Distinguishing Features

• HHS: Glucose typically >600 mg/dL, effective osmolality >320 mOsm/L, minimal or absent ketones, pH >7.30, bicarbonate >18 mEq/L 1
• DKA: Glucose typically >250 mg/dL, pH ≤7.30, bicarbonate <18 mEq/L, moderate to large ketones 1
• Hypothermia, if present, is a poor prognostic sign 1

Alternative Diagnoses to Consider

• Starvation ketosis: Plasma glucose mildly elevated or low, bicarbonate usually not <18 mEq/L 1
• Alcoholic ketoacidosis: Clinical history of alcohol use, glucose ranges from mildly elevated to hypoglycemia 1
• Other high anion gap metabolic acidoses: Lactic acidosis, salicylate ingestion, methanol, ethylene glycol, chronic renal failure 1
• Adipsic central diabetes insipidus: Rare but presents with hypernatremia, polyuria without polydipsia, and hyperosmolarity 5

Immediate Management Priorities

Initial Stabilization

• Fluid resuscitation is critical, particularly if HHS is suspected: isotonic saline 15-20 mL/kg/h in the first hour (1-1.5 liters in average adult) 1
• Insulin therapy: Intravenous insulin infusion for rapid-acting control of hyperglycemia 1, 6
• Electrolyte monitoring: Potassium levels must be monitored closely with IV insulin due to risk of life-threatening hypokalemia 1, 6
• Add 20-30 mEq/L potassium to fluids once renal function is assured 1

Monitoring for Complications

• Hypokalemia from insulin-induced intracellular potassium shift can cause respiratory paralysis, ventricular arrhythmia, and death 6
• Monitor for cerebral edema (rare in adults but catastrophic if occurs) 3
• Assess for vascular thrombotic complications from hyperosmolarity and dehydration 3