Diabetic peripheral neuropathy is a length-dependent, "dying-back" axonopathy: the longest fibres (here, a ~1.2 m tibial-nerve-scale axon running from the spinal cord to the toe) degenerate first and worst, producing the classic distal "stocking-glove" sensory loss. Two chronic-hyperglycemia mechanisms drive it, both real and well-established:
- Polyol-pathway / AGE injury to Schwann cells — excess glucose is shunted through aldose reductase to sorbitol, depleting myelin-maintaining metabolites and thinning the myelin sheath at nodes of Ranvier.
- Vasa nervorum microangiopathy — the small vessels feeding the nerve itself narrow, and the most distal, poorly-perfused segments become ischemic first, compounding demyelination with outright axonal loss.
Segment health is modelled as a length-dependent probability of injury:
burden = clamp((HbA1c − 5.5) × years × k, 0, 1)
risk(x) = burden × (x / L)^2 [x = distance from spinal cord, dying-back]
health(x) = 1 − risk(x) (ischemia toggle steepens the distal falloff)
For myelinated fibres, conduction is saltatory — the action potential jumps node-to-node, with velocity approximated by Rushton's rule v ≈ 6·d (d = axon diameter in μm, v in m/s). Demyelination lengthens the effective delay at each node (slowing v); once local health falls below a threshold the internode can no longer regenerate the impulse and conduction blocks — the fibre goes numb distal to that point, which is exactly why diabetic neuropathy first presents as loss of sensation in the toes, not the thigh.
Controls: the two sliders set cumulative metabolic injury; the ischemia toggle adds distal microvascular damage; "Fire action potential" sends a real impulse down the fibre so you can watch it slow through demyelinated internodes and stop (or succeed) at the point degeneration has reached.