Contrary to popular belief deranged lipid metabolism is the main cause of DKA. In essence DKA is caused by uncontrolled lipolysis in adipose tissue and uncontrolled ketogenesis in liver. Adipose tissue is present in regional depots such as subcutaneous upper and lower body and visceral fat. Under physiological conditions lipolysis is tightly controlled by lipases. Hormone-sensitive lipase and probably also adipose triglyceride lipase stimulate release of free fatty acids and glycerol into the circulation. This process is inhibited by insulin and low insulin levels increase lipolysis swiftly. The stress hormones, such as epinephrine, growth hormone and cortisol, stimulate lipolysis. It is plausible that dehydration also participates in the stimulation of lipolysis. These events take place in the course of hours and may rapidly triple or quadruple blood concentrations of free fatty acids.
Ketogenesis occurs in the liver by oxidation of free fatty acids to ketoacids/ketone bodies. Physiologically ketone bodies provide important fuel energy for the brain and other tissues under fasting, prolonged exercise and other conditions of fuel shortage. In DKA ketogenesis becomes uncontrolled and circulating levels of ketone bodies rise manifold. This occurs because of both increased supply of fatty acids to the liver and because low levels of insulin and high levels of glucagon in the liver promote ketogenesis. In normal individuals this unrestrained process is prevented by compensatory rises in insulin secretion, but this does not occur in type 1 diabetes. <Hg>
source :
Mogensen, C. E., 2007, Pharmacotherapy of Diabetes:New Developments Improving Life and Prognosis for Diabetic Patients, Springer Science + Business Media, LLC, New York.
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