Diabetic Ketoacidosis (DKA)

Disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency accompanied by an increase in the counter-regulatory hormones e.g. glucagon, adrenaline, cortisol and growth hormone

Aetiology

  • Serious complication of type 1 diabetes and, much less commonly, of type 2 diabetes

Insulin deficiency

  • Initial presentation of unknown diabetes
  • Non-adherence to insulin/poor self-management

Increased insulin demand

  • Infections: pneumonia, UTIs, cellulitis
  • Inflammatory: pancreatitis, cholecystitis
  • Intoxication: alcohol, cocaine, salicylate, methanol
  • Infarction: acute MI, stroke
  • Iatrogenic: steroids, surgery

Pathophysiology

Formation of ketone bodies

  • Formed in liver mitochondria (mainly acetoacetate and 3 hydroxybutyrate) from acetyl-CoA (which is from beta oxidation of fats)
  • Diffuse into the bloodstream and to peripheral tissues
  • Ketones are important molecules of energy metabolism for heart muscle and renal cortex
    • Converted back into acetyl-CoA, which enters TCA cycle
  • If supply of pyruvate/oxalonacetate is limited (e.g. if glycolysis is reduced, limiting glucose) the excess acetyl-CoA is diverted to ketones

Ketones in diabetes

  • Insulin normally inhibits lipolysis, reducing risk of ketone body overload
  • In T1DM, DKA is a danger if insulin supplementation is missed and hyperglycaemia ensues - amount of glucose taken up from the blood into tissues and amount of glycolysis will reduce, so body switches to fatty acid oxidation
  • DKA is more rare in T2DM where there is still some inhibition of lipolysis, but can occur as insulin resistance and deficiency increases, alongside increase in glucagon
  • Ketoacidosis can also occur in starvation - oxaloacetate is consumed for gluconeogenesis and when glucose is not avaliable fatty acids are oxidised to provide energy; the excess acetyl-CoA will be converted into ketones

Consequences

  • Excessive accumulation of ketone bodies can lead to acidosis
  • High glucose excretion creates an osmotic diuresis, resulting in electrolyte loss and dehydration; this decreases renal function and exacerbates acidosis
  • Can lead to coma, death

Clinical presentation

Osmotic related

  • Thirst and polyuria
  • Dehydration

Ketone body related

  • Flushed
  • Vomiting
  • Abdominal pain and tenderness
  • Increased respiratory rate
    • Kussmaul's respiration: deep, rapid breathing pattern associated with severe metabolic acidosis
  • Fruity (acetone) breath odor

Associated conditions

  • Underlying sepsis
  • Gastroenteritis

Investigations

Diagnosis is confirmed by demonstrating hyperglycaemia with ketonaemia or heavy ketonuria, and acidosis:
  • Ketonaemia ≳3 mmol/L, or significant ketouria (≳2 on standard urine stick)
  • Blood glucose >300-600 mg/dL or known DM
    • Euglycaemic DKA is possible if a patient has given themselves some insulin, but not enough to switch off ketogenesis
    • Euglycaemic DKA is also a rare complication of SGLT2i
  • Bicarbonate <18 mmol/L and/or venous pH <7.3

Other biochemistry

  • Potassium often >5.5 mmol/L but drops as soon has insulin is given - can cause hypokalaemia
    • Insulin promotes co-transport of potassium along with glucose into cells
  • Creatinine often raised
  • Sodium often low or low end of normal
  • Amylase often raised (rarely pancreatitis, origin can be salivery)
  • White cell count raised (median 25) - does not always equate infection, sign of inflammatory response

Management

Replace fluid losses

  • 1500mL NaCl 0.9% in the first hour
    • 1000mL in the first 30 minutes
    • 500mL in the second 30 minutes
  • 3000mL (+1500mL) NaCl by end of hour 2
  • 4000mL (+1000mL) NaCl by end of hour 4
  • Blood Glucose target
    • 200-250 mg/dL
    • If target achieved, lower IV insulin dose 0.05-0.1 units/kg

Replace electrolyte losses

  • NaCl 0.9% as above
  • IV Kalium
    • <3.0 mEq/L
      • Postpone insulin
      • KCl 75 mEq/L every 6 hours
    • 3.0-4.5 mEq/L
      • KCl 50 mEq/L every 6 hours
    • 4.5-6.0 mEq/L
      • KCl 25 mEq/L every 6 hours
    • >6.0 mEq/L
      • Postpone IV Kalium
      • Monitor every 6 hours
  • Bicarbonate rarely replaced
    • <7.0 → 100 mEq HCO3-
    • 7.0-7.1 → 50 mEq HCO3-
    • >7.1 → no correction

Restoration of acid-base balance

  • Bicarbonate rarely replaced as once the circulating volume is restored the metabolic acidosis is rapidly compensated

Insulin replacement

  • IV insulin 0.1 units/kg loading dose, then 0.1 units/kg/hour
  • Continue 'usual' SC daily basal insulin
  • Continue IV insulin until ketoacidosis has been resolved; to prevent hypoglycaemia give 10% glucose IV alongside the 0.9% NaCl once blood-glucose concentration falls below 14 mmol/L

Monitoring

  • Monitor blood-ketone and blood-glucose concentrations hourly
  • Blood gas and electrolytes every 2-4 hours

Other measures

  • Seek underlying cause e.g. infection if suspected
  • Patient may aspirate vomit so consider NG tube
  • Dehydration, increased blood viscosity and coagulability of DKA increase risk of thromboembolism - all patients should receive prophylactic LMWH

Prevention of recurrence

  • Education and support before discharge
  • Provide patient with ketone meter
  • Arrange DSN follow-up and inform GP

Complications

  • Cerebral oedema - mostly happens in children/YAs
  • Hypokalaemia can cause cardiac arrest and paralytic ileus
  • Aspiration pneumonia
  • ARDS