A 24-year-old woman with known type 1 diabetes mellitus presents with a 2-day history of polyuria, polydipsia, nausea, and vomiting. She also reports abdominal pain and increasing fatigue. She recently had a febrile illness and missed several doses of insulin. On examination, she is dehydrated, tachycardic, and hypotensive. Her breathing is deep and rapid, and a fruity odor is noted on her breath. She is drowsy but arousable. Laboratory investigations show blood glucose 380 mg/dL, arterial pH 7.15, serum bicarbonate 12 mmol/L, and elevated serum ketones (β-hydroxybutyrate). Serum potassium is 5.2 mmol/L with a high anion gap metabolic acidosis. Diagnosis?
Diagnosis is Diabetic Ketoacidosis (DKA).
1. Definition
- Diabetic ketoacidosis is a life-threatening acute complication of diabetes.
- It is characterized by:
- Hyperglycemia (≥200 mg/dL) or known diabetes
- Ketosis (β-hydroxybutyrate ≥3.0 mmol/L) preferred; urine ketones if unavailable
- Metabolic acidosis (pH <7.3 and/or HCO₃⁻ <18 mmol/L)
2. Etiology / Associations
- Absolute or relative insulin deficiency
- Common triggers:
- Infection (most common)
- Insulin omission or pump failure
- Infarction (MI, stroke)
- Intoxication (alcohol, drugs)
- Initial presentation of diabetes
- Other triggers:
- Surgery or trauma
- Pancreatitis
- Steroid therapy
- Pregnancy
- SGLT2 inhibitors (euglycemic DKA)
3. Pathophysiology
- Insulin deficiency → decreased glucose uptake → hyperglycemia
- Increased counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone)
- Increased gluconeogenesis and glycogenolysis
- Osmotic diuresis → dehydration and electrolyte loss
- Lipolysis → free fatty acids
- Liver converts free fatty acids into ketone bodies:
- β-hydroxybutyrate (dominant)
- Acetoacetate
- Acetone (fruity breath)
- Result: high anion gap metabolic acidosis
4. Clinical Features
4.1 General Features
- Polyuria
- Polydipsia
- Weight loss
- Fatigue
4.2 Gastrointestinal Features
- Nausea
- Vomiting
- Abdominal pain
4.3 Respiratory Features
- Kussmaul respiration (deep, rapid breathing)
4.4 Neurological Features
- Altered mental status (drowsiness to coma)
4.5 Other Features
- Fruity (acetone) breath
- Signs of dehydration (tachycardia, hypotension, dry mucosa)
5. Diagnosis
5.1 Diagnostic Framework
- Hyperglycemia (≥200 mg/dL) or known diabetes
- Ketosis (β-hydroxybutyrate ≥3.0 mmol/L)
- Metabolic acidosis (pH <7.3 and/or HCO₃⁻ <18 mmol/L)
5.2 Severity Classification
- Mild:
- pH 7.25–7.3
- HCO₃⁻ 15–18
- Alert
- Moderate:
- pH 7.0–7.24
- HCO₃⁻ 10–15
- Drowsy
- Severe:
- pH <7.0
- HCO₃⁻ <10
- Stupor or coma
5.3 Additional Findings
- High anion gap metabolic acidosis (supportive, not required)
- Serum potassium may be normal or high initially despite total body deficit
- Serum osmolality may be mildly to moderately elevated
- Elevated BUN and creatinine due to dehydration
6. Differential Diagnosis
- Hyperosmolar hyperglycemic state (HHS)
- Alcoholic ketoacidosis
- Starvation ketoacidosis
- Lactic acidosis
- Toxic ingestions (methanol, ethylene glycol)
- Renal failure (uremia)
7. Management
7.1 Core Principle
- Fluids → Potassium → Insulin → Treat underlying cause
7.2 Fluid Therapy
- Start with isotonic fluid:
- Balanced crystalloids preferred; 0.9% saline acceptable
- Initial dose: 15–20 mL/kg (~1 L in first hour)
- Continue and adjust based on volume status and corrected sodium
- When glucose <250 mg/dL:
- Add 5–10% dextrose
- Purpose: prevent hypoglycemia and allow continued insulin therapy
7.3 Potassium Management
- If potassium <3.5 mmol/L:
- Hold insulin
- Give IV potassium
- If potassium 3.5–5.0 mmol/L:
- Add potassium to IV fluids
- If potassium >5.5 mmol/L:
- Monitor closely
- Target potassium: 4.0–5.0 mmol/L
7.4 Insulin Therapy
- Start only if potassium ≥3.5 mmol/L
- IV insulin: 0.1 units/kg/hour
- Target glucose fall: 50–75 mg/dL/hour
- Continue insulin until ketone clearance and resolution of acidosis (not just glucose normalization)
- In selected uncomplicated mild DKA:
- Subcutaneous rapid-acting insulin may be used
7.5 Bicarbonate Therapy
- Not routine
- Consider only if pH <7.0
7.6 Phosphate Therapy
- Not routine
- Consider if:
- Phosphate <1.0 mmol/L
- Cardiorespiratory dysfunction or muscle weakness
7.7 Treat Underlying Cause
- Infection → antibiotics
- MI, stroke, pancreatitis → specific management
- Avoid unnecessary empiric therapy
8. Monitoring
- Blood glucose hourly
- Electrolytes (especially potassium) every 2–4 hours
- β-hydroxybutyrate if available
- ABG/VBG every 2–4 hours
- Urine output (>0.5 mL/kg/hour)
- Vitals and neurological status
9. Resolution Criteria
- β-hydroxybutyrate <0.6 mmol/L
- pH ≥7.3 or HCO₃⁻ ≥18 mmol/L
- Glucose <200 mg/dL or near-normal
- Patient clinically improved and able to eat
10. Complications
- Hypokalemia
- Hypoglycemia
- Cerebral edema (rare in adults)
- ARDS
- Thrombosis
- Hyperchloremic metabolic acidosis
11. Key Clinical Insight
- Polyuria + vomiting + abdominal pain + Kussmaul breathing + high anion gap acidosis = DKA
12. Key Exam Points
- β-hydroxybutyrate = best ketone marker
- Euglycemic DKA (SGLT2 inhibitors)
- Always check potassium before insulin
- Insulin continues until ketosis resolves
- Add dextrose when glucose <250 mg/dL
- Bicarbonate only in severe acidosis
- Most common trigger = infection
- Death due to dehydration and electrolyte imbalance