From the Guidelines
In the pathophysiology of diabetic ketoacidosis (DKA), the initial effect of insulin deficiency is that serum levels of glycerol and free fatty acids (FFAs) increase. This occurs because insulin normally suppresses lipolysis in adipose tissue. When insulin is deficient, this inhibitory effect is lost, leading to increased breakdown of triglycerides in fat cells. The breakdown releases glycerol and FFAs into the bloodstream. The elevated FFAs are then taken up by the liver and converted to ketone bodies (acetoacetate, beta-hydroxybutyrate, and acetone) through beta-oxidation. This process happens early in the development of DKA, before the other effects like increased gluconeogenesis from amino acids or significant ketone accumulation. The increased lipolysis and subsequent rise in serum glycerol and FFAs represent the first metabolic consequence of insulin deficiency that sets the stage for the ketoacid production that characterizes DKA, as supported by studies such as 1.
Some key points to consider in the pathophysiology of DKA include:
- Insulin deficiency leads to increased lipolysis and release of free fatty acids into the circulation 1
- The combination of insulin deficiency and increased counterregulatory hormones leads to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues 1
- The use of bicarbonate in people with DKA has been shown to make no difference in the resolution of acidosis or time to discharge, and its use is generally not recommended 1
Overall, the initial effect of insulin deficiency in DKA is the increase in serum levels of glycerol and free fatty acids, which sets the stage for the development of ketoacidosis.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Initial Effect of Insulin Deficiency in DKA
The initial effect of insulin deficiency in the pathophysiology of Diabetic Ketoacidosis (DKA) can be understood by examining the role of insulin in glucose and lipid metabolism.
- Insulin plays a crucial role in regulating blood glucose levels by facilitating the uptake of glucose into cells and inhibiting the production of glucose in the liver.
- In the absence of insulin, the body begins to break down fat for energy, leading to an increase in serum levels of glycerol and free fatty acids (FFAs) 2, 3.
- This increase in FFAs is a key event in the pathogenesis of DKA, as it leads to the production of ketone bodies, which can cause metabolic acidosis.
- The correct answer is: Serum levels of glycerol and free fatty acids (FFAs) increase.
Mechanisms of Insulin Deficiency
The mechanisms by which insulin deficiency leads to the initial effects in DKA are complex and involve multiple pathways.
- Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes, and can lead to hyperglycemia and the subsequent development of DKA 4, 5.
- The increase in FFAs can also impair insulin secretion, creating a vicious cycle that exacerbates the condition 3.
- Glucagon excess can stimulate hepatic gluconeogenesis, further contributing to hyperglycemia and the development of DKA.
Key Findings
Key findings from the studies include: