# Diabetic Peripheral Neuropathy Mechanism Explorer

Authors: Brice Edelman and Jeffrey Skolnick.
Work in progress. Copied snapshot: 2026-09-14.
A research collection about structural injury to human peptidergic sensory fibers in diabetes.

## Entry points
- [JSON index](https://bricee98.github.io/dpn-mechanism-explorer/data/index.json): all reports and format paths.
- [Formats and interpretation](https://bricee98.github.io/dpn-mechanism-explorer/agents.html): fields and probability semantics.
- [Probability method](https://bricee98.github.io/dpn-mechanism-explorer/sources/probability_method.md): complete source definitions.
- [Coverage](https://bricee98.github.io/dpn-mechanism-explorer/sources/coverage.md): source coverage notes.

JSON paths are relative to https://bricee98.github.io/dpn-mechanism-explorer/, not to data/.
Conditional probabilities assume all preceding claims; cumulative values are products.
Scenario ranges are sensitivity, not confidence intervals. Hypotheses overlap.
Read the full causal proposition and source report for scope, evidence, and qualifications.
The README, research prompts, goals, and external internal-note dependencies are not included.

## Reports
- [01. Excess polyol flux and impaired sorbitol disposal](https://bricee98.github.io/dpn-mechanism-explorer/sources/01_polyol_flux.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/01_polyol_flux.json)
- [02. Excess glucosamine and hexosamine-associated metabolic stress](https://bricee98.github.io/dpn-mechanism-explorer/sources/02_glucosamine_hexosamine.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/02_glucosamine_hexosamine.json)
- [03. Glycated extracellular matrix prevents terminal replacement](https://bricee98.github.io/dpn-mechanism-explorer/sources/03_extracellular_matrix_glycation.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/03_extracellular_matrix_glycation.json)
- [04. Persistent RAGE signaling causes structural axon injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/04_rage_signaling.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/04_rage_signaling.json)
- [05. Intracellular methylglyoxal contributes to terminal injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/05_methylglyoxal_carbonyl_stress.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/05_methylglyoxal_carbonyl_stress.json)
- [06. Glucose-driven respiratory over-reduction and superoxide](https://bricee98.github.io/dpn-mechanism-explorer/sources/06_glucose_mitochondrial_overload.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/06_glucose_mitochondrial_overload.json)
- [07. Insufficient usable ATP in distal sensory axons](https://bricee98.github.io/dpn-mechanism-explorer/sources/07_bioenergetic_insufficiency.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/07_bioenergetic_insufficiency.json)
- [08. Fatty-acid delivery and neuronal mitochondrial depolarization](https://bricee98.github.io/dpn-mechanism-explorer/sources/08_fatty_acid_delivery.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/08_fatty_acid_delivery.json)
- [09. Oxidized LDL, neuronal LOX-1 and NADPH-oxidase injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/09_oxidized_ldl.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/09_oxidized_ldl.json)
- [10. Deoxysphingolipid accumulation in the sensory-neuron unit](https://bricee98.github.io/dpn-mechanism-explorer/sources/10_serine_deoxysphingolipids.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/10_serine_deoxysphingolipids.json)
- [11. Excess canonical ceramides in neurons or Schwann cells](https://bricee98.github.io/dpn-mechanism-explorer/sources/11_canonical_ceramides.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/11_canonical_ceramides.json)
- [12. Loss of neuronal insulin/IGF trophic support](https://bricee98.github.io/dpn-mechanism-explorer/sources/12_insulin_igf_trophic_deficit.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/12_insulin_igf_trophic_deficit.json)
- [13. C-peptide deficiency removes nerve support](https://bricee98.github.io/dpn-mechanism-explorer/sources/13_c_peptide_deficiency.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/13_c_peptide_deficiency.json)
- [14. Insufficient target-derived NGF/TrkA support](https://bricee98.github.io/dpn-mechanism-explorer/sources/14_ngf_trophic_support.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/14_ngf_trophic_support.json)
- [15. Inadequate microvascular oxygen or fuel delivery](https://bricee98.github.io/dpn-mechanism-explorer/sources/15_microvascular_ischemia.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/15_microvascular_ischemia.json)
- [16. DAG-dependent vascular PKCβ activity reduces nerve supply](https://bricee98.github.io/dpn-mechanism-explorer/sources/16_pkc_vascular_signaling.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/16_pkc_vascular_signaling.json)
- [17. Abnormal Remak Schwann-cell metabolic output injures unmyelinated axons](https://bricee98.github.io/dpn-mechanism-explorer/sources/17_schwann_metabolic_support.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/17_schwann_metabolic_support.json)
- [18. Insufficient or low-quality mitochondrial supply from satellite glia](https://bricee98.github.io/dpn-mechanism-explorer/sources/18_satellite_glial_mitochondrial_transfer.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/18_satellite_glial_mitochondrial_transfer.json)
- [19. Excess peripheral TNF-receptor or TLR4 signaling](https://bricee98.github.io/dpn-mechanism-explorer/sources/19_tnf_tlr4_inflammation.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/19_tnf_tlr4_inflammation.json)
- [20. Failure of macrophage dead-cell clearance](https://bricee98.github.io/dpn-mechanism-explorer/sources/20_loss_of_protective_macrophages.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/20_loss_of_protective_macrophages.json)
- [21. NLRP3-associated gasdermin-D membrane injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/21_inflammasome_pyroptosis.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/21_inflammasome_pyroptosis.json)
- [22. Complement-mediated vascular or glial membrane injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/22_complement_microvascular_injury.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/22_complement_microvascular_injury.json)
- [23. Persistent ER-sensor signaling impairs terminal maintenance](https://bricee98.github.io/dpn-mechanism-explorer/sources/23_er_stress.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/23_er_stress.json)
- [24. Slow completion of intracellular autophagic disposal](https://bricee98.github.io/dpn-mechanism-explorer/sources/24_autophagy_mitophagy.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/24_autophagy_mitophagy.json)
- [25. Abnormal mitochondrial fission or fusion impairs terminal maintenance](https://bricee98.github.io/dpn-mechanism-explorer/sources/25_mitochondrial_dynamics.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/25_mitochondrial_dynamics.json)
- [26. Impaired axonal transport creates a local cargo imbalance](https://bricee98.github.io/dpn-mechanism-explorer/sources/26_axonal_transport.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/26_axonal_transport.json)
- [27. SARM1 catalytic activity contributes to terminal destruction](https://bricee98.github.io/dpn-mechanism-explorer/sources/27_sarm1_axon_destruction.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/27_sarm1_axon_destruction.json)
- [28. Excess PARP1 catalysis contributes to terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/28_parp_nad_depletion.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/28_parp_nad_depletion.json)
- [29. Iron-dependent lipid peroxidation causes ferroptotic membrane injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/29_ferroptosis.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/29_ferroptosis.json)
- [30. Somal apoptotic execution contributes to terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/30_neuronal_soma_apoptosis.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/30_neuronal_soma_apoptosis.json)
- [31. Excess electrogenic cation entry contributes to terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/31_hyperexcitability_calcium.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/31_hyperexcitability_calcium.json)
- [32. Altered skin matrix and trophic support restrict terminal replacement](https://bricee98.github.io/dpn-mechanism-explorer/sources/32_skin_repair_environment.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/32_skin_repair_environment.json)
- [33. Persistent senescence-like secretory signaling contributes to terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/33_senescence_sasp.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/33_senescence_sasp.json)
- [34. Altered gut-derived chemical exposure contributes to terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/34_microbiome_metabolites.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/34_microbiome_metabolites.json)
- [35. Rapid correction of chronic hyperglycemia precipitates structural small-fiber injury](https://bricee98.github.io/dpn-mechanism-explorer/sources/35_rapid_glycemic_correction.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/35_rapid_glycemic_correction.json)
- [36. Mechanical loading and reduced nerve tolerance in early diabetes](https://bricee98.github.io/dpn-mechanism-explorer/sources/36_mechanical_compression.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/36_mechanical_compression.json)
- [37. Metformin-associated B12 deficiency and further terminal loss](https://bricee98.github.io/dpn-mechanism-explorer/sources/37_metformin_b12_deficiency.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/37_metformin_b12_deficiency.json)
- [38. Renal retention and additional terminal loss in advanced CKD](https://bricee98.github.io/dpn-mechanism-explorer/sources/38_kidney_failure_uremic_exposure.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/38_kidney_failure_uremic_exposure.json)
- [39. Oxidant and nitrosative damage exceeds defense and repair](https://bricee98.github.io/dpn-mechanism-explorer/sources/39_oxidative_nitrosative_injury.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/39_oxidative_nitrosative_injury.json)
- [40. Persistent gene regulation sustains injury after the exposure improves](https://bricee98.github.io/dpn-mechanism-explorer/sources/40_epigenetic_memory.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/40_epigenetic_memory.json)
- [41. Deep or sustained hypoglycemia exhausts axonal fuel](https://bricee98.github.io/dpn-mechanism-explorer/sources/41_hypoglycemic_energy_failure.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/41_hypoglycemic_energy_failure.json)
- [42. Glucose fluctuations add injury beyond average exposure](https://bricee98.github.io/dpn-mechanism-explorer/sources/42_glycemic_variability.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/42_glycemic_variability.json)
- [43. Insufficient protective membrane lipids and lipid mediators](https://bricee98.github.io/dpn-mechanism-explorer/sources/43_protective_lipid_deficiency.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/43_protective_lipid_deficiency.json)
- [44. Intrinsic growth restraint prevents adequate terminal replacement](https://bricee98.github.io/dpn-mechanism-explorer/sources/44_intrinsic_growth_restriction.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/44_intrinsic_growth_restriction.json)
- [45. Aggregated amylin exposes sensory neurons to a circulating peptide toxin](https://bricee98.github.io/dpn-mechanism-explorer/sources/45_amylin_aggregation.md) · [JSON](https://bricee98.github.io/dpn-mechanism-explorer/data/45_amylin_aggregation.json)