Diabetic Ketoacidosis
Diabetic ketoacidosis – DKA
DKA arises due to absolute or relative insulin deficiency combined with physiological stressors. Major triggers include:
Insulin Deficiency
- Missed insulin doses (intentional or unintentional)
- Insulin pump failure (common in adolescents)
- Inadequate basal insulin coverage
- New onset of diabetes (often type 1)
Infections
- Gastroenteritis
- Pneumonia
- UTI
- Diabetic foot infection
- Sepsis
Other Physiological Stressors
- Pancreatitis
- Pregnancy
- Trauma or surgery
- Myocardial infarction or stroke
- Substance use (alcohol, cocaine)
Medications
- Corticosteroids
- Sympathomimetics
- SGLT2 inhibitors (can cause euglycaemic DKA)
- Atypical antipsychotics
- Checkpoint inhibitors (e.g., nivolumab, pembrolizumab)
- Protease inhibitors (e.g., ritonavir)
- Pentamidine
- Calcineurin inhibitors (e.g., tacrolimus, cyclosporine)
Evaluation of the Cause of DKA
A targeted history and physical examination are often sufficient. If a clear cause (e.g., medication non-adherence) is identified, extensive investigations may be unnecessary. However, certain clinical features require more scrutiny:
Infection vs Non-infectious Inflammation
- DKA commonly causes leukocytosis, which may be misleading.
- Consider infection if there is:
- Fever
- Marked left shift on differential
- Severe leukocytosis (WBC > 20,000–25,000/mm³)
(PMID: 3101715)
Abdominal Pain: Is It from DKA or Something Else?
Abdominal pain is common in DKA, but may also indicate a primary intra-abdominal pathology.
Clues suggesting a non-DKA cause:
- Severe abdominal pain despite only mild metabolic derangement (PMID: 12040551)
- Abdominal pain that fails to improve after initial DKA correction
Recommended approach:
- Treat DKA aggressively first, monitor clinical improvement
- Perform serial abdominal exams
- If pain persists or worsens, proceed to CT abdomen or surgical referral
Altered Mental Status: Consider Neurological Causes
Altered consciousness in DKA is common when serum osmolality > 320 mOsm/kg, but if mental status is:
- Disproportionate to metabolic disturbance
- Not improving with treatment
- Accompanied by focal signs or seizures
→ Then consider alternate neurological causes:
- CNS infection (e.g., meningitis, encephalitis)
- Intracranial haemorrhage or stroke
(PMID: 25905280)
Also monitor for:
- Cerebral oedema, especially in younger patients, or if neurological status worsens during treatment
Diagnostic Criteria for DKA
- pH < 7.3
- HCO₃⁻ < 15 mmol/L
- Positive ketones (urine or serum)
- Elevated anion gap metabolic acidosis
- Hyperglycaemia (often >11 mmol/L, though may be normal in euglycaemic DKA)
History & Examination
Key Features to Assess
- Precipitant: infection, non-compliance, myocardial infarction, pancreatitis, GI illness
- Symptoms:
- Polyuria, polydipsia, nausea/vomiting, abdominal pain
- Fatigue, weakness, altered mental status
- In children: headache, irritability, thermal instability
Physical Exam
- Volume status: hypotension, tachycardia
- Respiratory: Kussmaul breathing, fruity (acetone) breath
- Neurological: assess GCS; confusion may indicate cerebral oedema
- Other: signs of infection or acute illness
Investigations
- ABG – to assess acidosis
- U&Es, glucose, serum osmolality
- Urine dipstick – for ketones and infection
- Serum ketones
- ECG, CXR, FBC – to evaluate for underlying infection/ischemia
- Pregnancy test – in women of childbearing age
- C-peptide and autoantibodies (GAD, IA2) – to differentiate from type 1 diabetes (post-recovery)
Management of DKA
Initial Resuscitation
- Secure airway, provide oxygen if needed
- IV access, commence fluid resuscitation:
- 0.9% NaCl bolus (20 mL/kg), adjust for age, comorbidities
- Urinary catheterisation if unable to void
Metabolic Correction
Fluids
- Use balanced crystalloid solutions (e.g., Plasma-Lyte, Hartmann’s) if available
- Switch to 5% dextrose when BGL <14 mmol/L
Insulin
- Start continuous IV insulin infusion (no bolus):
- 0.05–0.1 units/kg/hr
- Aim to reduce glucose by 1–2 mmol/L/hr
- Continue insulin until ketones clear and patient is eating
Electrolytes
- Potassium: Replace as needed — total body potassium is always depleted
- Hold insulin if K⁺ <3.3 mmol/L until corrected
- Sodium: Correct for hyperglycaemia if needed
- Bicarbonate: Rarely needed — only for pH <6.9
Monitor
- BGL, VBG, serum ketones, electrolytes every 1–2 hours initially
- Watch for complications: cerebral oedema, hypoglycaemia, arrhythmia, thrombosis
Identify and Treat Underlying Cause
- Common precipitants:
- Infection (UTI, pneumonia)
- Medication non-compliance
- Myocardial infarction, CVA
- Acute pancreatitis
- Pregnancy (check β-hCG in women)
Complications to Monitor
- Hypoglycaemia
- Cerebral oedema
- Hyperchloraemic acidosis (especially with NS)
- Electrolyte derangements (K⁺, Na⁺, phosphate)
- Arrhythmias
- Infection/sepsis
- Thrombosis (DVT/PE)
Ketosis-prone diabetes (KPD)
Reference: AFP – Ketoacidosis in a Patient with Type 2 Diabetes. Vol 44(1), Jan–Feb 2015.
- Traditionally, diabetic ketoacidosis (DKA) has been associated with type 1 diabetes.
- However, emerging evidence reveals that DKA can also occur in type 2 diabetes, particularly in specific populations such as those of African, African-American, and South Asian descent.
- This form is often called:
- Ketosis-prone type 2 diabetes
- Flatbush diabetes
- Type 1.5 diabetes
Clinical Characteristics
- Demographics:
- Middle-aged adults
- Often obese, hypertensive
- Strong family history of type 2 diabetes
- Clinical signs of insulin resistance (e.g. acanthosis nigricans)
- Mechanism:
- A transient insulin secretory defect superimposed on chronic insulin resistance
- Often negative for autoimmune markers (GAD, IA2 antibodies)
- C-peptide levels may recover after resolution of DKA
- South African data: ~50% of DKA cases were found to have type 2 diabetes (not autoimmune).
Consider KPD if:
- Patient is middle-aged or older, often obese
- Clinical signs of insulin resistance (e.g., acanthosis nigricans)
- No prior diabetes diagnosis, but presenting in DKA
- Negative for autoimmune markers (e.g., GAD, IA-2)
- Preserved or recoverable C-peptide levels after resolution
Hospital Course
- Initially presents as DKA
- Insulin resistance typically improves with treatment
- Patients often recover beta-cell function during recovery (evidenced by rising C-peptide)
- Many no longer require insulin long term, and can be maintained on oral hypoglycaemic agents