Boris Draznin

“The mechanisms that underlie the increased production of ketones recently have been discussed in a number of reviews on DKA.12,14 The combination of insulin deficiency and increased concentration of counterregulatory hormones causes the activation of hormone-sensitive lipase in adipose tissue. The increased activity of tissue lipase causes a breakdown of triglyceride into glycerol and free fatty acids (FFAs). In the liver, FFAs are oxidized to ketone bodies, a process predominantly stimulated by glucagon.15 Increased concentration of glucagon lowers the hepatic levels of malonyl coenzyme A (CoA) by blocking the conversion of pyruvate to acetyl CoA through inhibition of acetyl CoA carboxylase,15 the first rate-limiting enzyme in de novo fatty acid synthesis. Malonyl CoA inhibits carnitine palmitoyl-transferase I (CPT I), the rate-limiting enzyme for transesterification of fatty acyl CoA to fatty acyl carnitine, allowing oxidation of fatty acid to ketone bodies.15 The increased fatty acyl CoA in DKA leads to increased ketogenesis in DKA.15 Increased production of ketone bodies (acetoacetate and β-hydroxybutyrate) leads to ketonemia and metabolic acidosis.”
― Boris Draznin, Managing Diabetes and Hyperglycemia in the Hospital Setting: A Clinician's Guide