Diabetic Ketoacidosis (DKA)

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

1. Diabetic ketoacidosis is a life-threatening acute complication of diabetes.
2. It is characterized by:
1. Hyperglycemia (≥200 mg/dL) or known diabetes
2. Ketosis (β-hydroxybutyrate ≥3.0 mmol/L) preferred; urine ketones if unavailable
3. Metabolic acidosis (pH <7.3 and/or HCO₃⁻ <18 mmol/L)

2. Etiology / Associations

1. Absolute or relative insulin deficiency
2. Common triggers:
1. Infection (most common)
2. Insulin omission or pump failure
3. Infarction (MI, stroke)
4. Intoxication (alcohol, drugs)
5. Initial presentation of diabetes
3. Other triggers:
1. Surgery or trauma
2. Pancreatitis
3. Steroid therapy
4. Pregnancy
5. SGLT2 inhibitors (euglycemic DKA)

3. Pathophysiology

1. Insulin deficiency → decreased glucose uptake → hyperglycemia
2. Increased counter-regulatory hormones (glucagon, cortisol, catecholamines, growth hormone)
3. Increased gluconeogenesis and glycogenolysis
4. Osmotic diuresis → dehydration and electrolyte loss
5. Lipolysis → free fatty acids
6. Liver converts free fatty acids into ketone bodies:
1. β-hydroxybutyrate (dominant)
2. Acetoacetate
3. Acetone (fruity breath)
7. Result: high anion gap metabolic acidosis

4. Clinical Features

4.1 General Features

1. Polyuria
2. Polydipsia
3. Weight loss
4. Fatigue

4.2 Gastrointestinal Features

1. Nausea
2. Vomiting
3. Abdominal pain

4.3 Respiratory Features

1. Kussmaul respiration (deep, rapid breathing)

4.4 Neurological Features

1. Altered mental status (drowsiness to coma)

4.5 Other Features

1. Fruity (acetone) breath
2. Signs of dehydration (tachycardia, hypotension, dry mucosa)

5. Diagnosis

5.1 Diagnostic Framework

1. Hyperglycemia (≥200 mg/dL) or known diabetes
2. Ketosis (β-hydroxybutyrate ≥3.0 mmol/L)
3. Metabolic acidosis (pH <7.3 and/or HCO₃⁻ <18 mmol/L)

5.2 Severity Classification

1. Mild:
1. pH 7.25–7.3
2. HCO₃⁻ 15–18
3. Alert
2. Moderate:
1. pH 7.0–7.24
2. HCO₃⁻ 10–15
3. Drowsy
3. Severe:
1. pH <7.0
2. HCO₃⁻ <10
3. Stupor or coma

5.3 Additional Findings

1. High anion gap metabolic acidosis (supportive, not required)
2. Serum potassium may be normal or high initially despite total body deficit
3. Serum osmolality may be mildly to moderately elevated
4. Elevated BUN and creatinine due to dehydration

6. Differential Diagnosis

1. Hyperosmolar hyperglycemic state (HHS)
2. Alcoholic ketoacidosis
3. Starvation ketoacidosis
4. Lactic acidosis
5. Toxic ingestions (methanol, ethylene glycol)
6. Renal failure (uremia)

7. Management

7.1 Core Principle

1. Fluids → Potassium → Insulin → Treat underlying cause

7.2 Fluid Therapy

1. Start with isotonic fluid:
1. Balanced crystalloids preferred; 0.9% saline acceptable
2. Initial dose: 15–20 mL/kg (~1 L in first hour)
3. Continue and adjust based on volume status and corrected sodium
4. When glucose <250 mg/dL:
1. Add 5–10% dextrose
2. Purpose: prevent hypoglycemia and allow continued insulin therapy

7.3 Potassium Management

1. If potassium <3.5 mmol/L:
1. Hold insulin
2. Give IV potassium
2. If potassium 3.5–5.0 mmol/L:
1. Add potassium to IV fluids
3. If potassium >5.5 mmol/L:
1. Monitor closely
4. Target potassium: 4.0–5.0 mmol/L

7.4 Insulin Therapy

1. Start only if potassium ≥3.5 mmol/L
2. IV insulin: 0.1 units/kg/hour
3. Target glucose fall: 50–75 mg/dL/hour
4. Continue insulin until ketone clearance and resolution of acidosis (not just glucose normalization)
5. In selected uncomplicated mild DKA:
1. Subcutaneous rapid-acting insulin may be used

7.5 Bicarbonate Therapy

1. Not routine
2. Consider only if pH <7.0

7.6 Phosphate Therapy

1. Not routine
2. Consider if:
1. Phosphate <1.0 mmol/L
2. Cardiorespiratory dysfunction or muscle weakness

7.7 Treat Underlying Cause

1. Infection → antibiotics
2. MI, stroke, pancreatitis → specific management
3. Avoid unnecessary empiric therapy

8. Monitoring

1. Blood glucose hourly
2. Electrolytes (especially potassium) every 2–4 hours
3. β-hydroxybutyrate if available
4. ABG/VBG every 2–4 hours
5. Urine output (>0.5 mL/kg/hour)
6. Vitals and neurological status

9. Resolution Criteria

1. β-hydroxybutyrate <0.6 mmol/L
2. pH ≥7.3 or HCO₃⁻ ≥18 mmol/L
3. Glucose <200 mg/dL or near-normal
4. Patient clinically improved and able to eat

10. Complications

1. Hypokalemia
2. Hypoglycemia
3. Cerebral edema (rare in adults)
4. ARDS
5. Thrombosis
6. Hyperchloremic metabolic acidosis

11. Key Clinical Insight

1. Polyuria + vomiting + abdominal pain + Kussmaul breathing + high anion gap acidosis = DKA

12. Key Exam Points

1. β-hydroxybutyrate = best ketone marker
2. Euglycemic DKA (SGLT2 inhibitors)
3. Always check potassium before insulin
4. Insulin continues until ketosis resolves
5. Add dextrose when glucose <250 mg/dL
6. Bicarbonate only in severe acidosis
7. Most common trigger = infection
8. Death due to dehydration and electrolyte imbalance