Fatty Acids and Ketone Bodies

Insulin deficiency results in lipolysis increasing free fatty acid production. The fatty acids are then degraded through eight stages within the mitochondria. Each stage releases one molecule of acetyl-co-enzyme A. In the absence of insulin more of this is formed than can enter the citric acid cycle and the acetyl-co-enzyme is reduced to beta hydroxy-butyric acid or decarboxylated to acetoacetic acid and subsequently to acetone. The acetoacetic acid also reduces the glucose uptake by cells.

Beta hydroxy-butyric acid, acetoacetic acid and acetone are acids causing in part the acidosis. Beta hydroxy-butyric acid also causes nausea and vomiting, increasing the dehydration.

The increase in cortisol, catecholamines and growth hormone activates hormone-sensitive lipase which leads to lipolysis causing the release of free-fatty acids which are taken up by the liver.