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