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In individuals with T2D, epigenetic modifications, specifically increased DNA methylation of the GLP-1R gene, reduce receptor expression, impairing the function of GLP-1 and lowering insulin secretion
When oxygen availability is limited, glucose is the most metabolically efficient fuel, and during myocardial ischemia, the ratio of acetyl-CoA/CoA in mitochondria increases, leading to the activation of pyruvate dehydrogenase (PDH) kinase, which in turn phosphorylates PDH to inhibit its activity
Weight loss mechanism: Much of the liver benefit likely comes through weight loss, which is highly effective for fatty liver disease
Medication Nonadherence Ensuring GLP-1s are only prescribed to the appropriate members is proving to be difficult enough, but recent data is also showing that 58% of patients are discontinuing them before reaching meaningful levels of weight loss
