The editorial spine
The three pillars
Heart disease, type 2 diabetes and Alzheimer’s present as separate specialties with separate clinics. Follow each one down far enough and you arrive at the same three failures.
27 of 65 compounds filed against a pillar10 with no published human dose
Why three and not thirty
They are not independent, and the order matters less than the fact that the thing closes on itself. Sustained inflammation interferes with the insulin signal, so cells answer the same amount of insulin with less. The body compensates by making more of it, and chronically high insulin drives storage and inflammatory signalling of its own. Mitochondria inside overloaded cells return less usable energy and more of the reactive by-products that provoke inflammation, which is where the circuit rejoins itself.
Each step in that circuit belongs to a different specialty. The circuit belongs to none of them, and that is the whole reason for organising a publication around three failures rather than around the twenty-odd diseases they surface as.
What is actually sold against them
This publication has no standing to settle the biology and does not try to. A pillar page here asks the narrower question it can answer: what gets sold on that rationale, and whether anything was ever published behind it. Each compound is filed on the pitch its own entry describes, never on a chain of inference. 27 of the 65 compounds in this reference are filed against one of the three, and 10 of those have no published human dose to compare against at all.
The distribution runs opposite to the sales pitch. Insulin resistance is the least fashionable of the three and carries the most behind it, because it is where the approved drugs are: 13 compounds, 2 of them with nothing published. Mitochondrial dysfunction has the most compelling mechanism story and the thinnest record under what is sold on it, at 5 of 8. The better the story reads, the less of it has been measured in a person.
The same figures for all 65 compounds, pillar or no pillar, sit in one table at what circulates vs what was studied, and each one has a card in the compound reference.