Disease as setpoint failure (the derived law)

Metabolic disease here is not a local lesion -- it is a defended setpoint that drifted or crossed to a pathological basin. One derived law covers all of it: a loop-gain drop d lowers the effective stiffness g→g(1−d), which SHRINKS the barrier and LOWERS the crossing threshold, so a chronic forcing then drifts or crosses the setpoint.

The pathology frame. The same Kramers/spinodal kernel the framework uses for carcinogenesis is applied at the LOOP level: g_eff = g(1−d); barrier = g_eff²/4; spinodal = 2(g_eff/3)^1.5; the state crosses iff the chronic forcing exceeds the reduced spinodal. Shape [V]; cited anchors [L]; absolute incidence [O].

The law, from R19

g_eff = g*(1-d); barrier=g_eff^2/4; spinodal=2*(g_eff/3)^1.5; crossed iff |forcing|>spinodal

Two regimes follow: a SUB-spinodal chronic forcing DRIFTS the defended setpoint (basin intact, defended at a shifted value); a SUPRA-spinodal forcing CROSSES to the disease basin (regulation lost). Which regime a disease is in is a computed result, not an assumption.

Why one law for many diseases

Type-2 diabetes, obesity, and metabolic syndrome are not separate mechanisms in this view -- they are the same loop-gain-drop-plus-chronic-forcing kernel acting on different nodes (glucose, adiposity, and their shared upstream signalling). The next four chapters instantiate the law per disease.

Composition with the disease whitepaper

monogenic lesion = imported loop parameter (cited); systemic trajectory = computed here. Acquired/polygenic disease = loop dysregulation, owned here.