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Furthermore, from a cardiovascular point of view, metformin is known to reduce cardiovascular complications related to diabetes [53] and therefore may contribute to reducing such complications among NAFLD patients who are more prone to develop coronary, cerebrovascular, and peripheral vascular disease independently of multiple CVD risk factors [54]

S1P amplifies this effect by binding to hemoglobin complexes associated with 2,3-BPG, pushing them toward the T-state, a structural configuration favoring oxygen release ( 2.2.2 AMPK activation enhances 2,3-BPG mutase phosphorylation Red blood cells must rapidly adjust their internal metabolism to maintain effective oxygen delivery during hypoxia