In adults with prediabetes, long-term use of PCSK9 inhibitors may be linked to a slight increase in the rate of developing type 2 diabetes compared to those not taking these drugs, but the difference...
Mechanism
Synthesis from 1 study
This drug increases how many cholesterol-carrying particles enter insulin-producing cells in the pancreas. In people already struggling to control blood sugar, this extra cholesterol stresses those cells, making them worse at releasing insulin and pushing them closer to diabetes. For most people,...
Most probable mechanism
When a drug blocks a protein that normally removes LDL receptors, more receptors build up on liver and pancreas cells. In the pancreas, this causes too much cholesterol to enter insulin-producing cells, which stresses them and makes them less able to release insulin. This effect is strongest in people who already have high blood sugar, pushing them closer to diabetes, but doesn't affect most people's blood sugar overall.
PCSK9 inhibition increases the number of LDL receptors on the surface of hepatocytes and pancreatic beta-cells
Increased LDL receptor density enhances the uptake of low-density lipoprotein into pancreatic beta-cells
Intracellular cholesterol accumulates in pancreatic beta-cells, disrupting membrane fluidity and endoplasmic reticulum function
Cholesterol overload induces cellular stress, reducing glucose-stimulated insulin secretion and impairing beta-cell function
In individuals with pre-existing prediabetes and elevated fasting glucose, beta-cell dysfunction progresses to overt diabetes due to reduced insulin reserve and compensatory failure
Evidence from Studies
Supporting (1)
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