Interesting to see the mechanisms finally being pinned down to micro-clots and mTOR signaling. The 41% risk reduction with Metformin is a significant signal regarding the metabolic nature of the condition. The critical takeaway for anyone reading this for personal management is the section on rehabilitation: "exercise that is not carefully supervised can worsen inflammation." The shift from "graded exercise therapy" to "pacing" is a massive clinical pivot that likely prevents a lot of patients from getting worse.