Ketoacidosis, diabetic

Diabetic ketoacidosis (DKA) is a severe complication characteristic of type I diabetes. Around 16% of patients die during a coma when this complication arises. Insufficient insulin concentration or the disappearance of its biological effect, along with an increase in counter-insulin hormone concentrations, are the most common causes. Risk factors include inadequate insulin dose, stress, surgical procedures, injuries, alcohol abuse, pregnancy, and concomitant diseases.

Mechanism of Activation

The process of diabetic ketoacidosis activates due to gluconeogenesis, triggered by a lack of insulin and an excess of glucagon. Glucagon activates protein kinase, phosphorylating fructose 2,6-bisphosphatase, which reduces the concentration of fructose 2,6-diphosphate and inhibits glycolysis. Conversely, gluconeogenesis activates, leading to an increase in blood glucose concentration.

Pathophysiology

• Impaired Glucose Transport: During hypoinsulinism, glucose transport into cells disrupts.
• Increased Hyperglycemia: Active gluconeogenesis and inhibition of glucose utilization in cells significantly intensify hyperglycemia.
• Intensified Ketogenesis: Ketogenesis intensifies greatly due to:
  1. Activation of lipolysis in adipose tissue and the release of fatty acids into the blood and liver.
  2. Activation of hepatocyte carnitine acyltransferase I, influenced by glucagon, which intensifies ketogenesis. An increase in liver carnitine concentration, under the influence of glucagon, also promotes this process.

Consequences of DKA

During diabetic ketoacidosis, pathways of acetyl-CoA utilization become ineffective or inhibited, except those that promote ketosis and cholesterol synthesis. Ketones, being organic acids, cause metabolic acidosis, which drives water and electrolyte loss, leading to extracellular dehydration. This, in turn, promotes cellular dehydration, hemoconcentration, and peripheral circulatory insufficiency leading to hypotension. The decreasing renal blood flow can lead to anuria and shock. Ion loss can cause arrhythmia, further exacerbating circulatory insufficiency.