Snapshot 14 September 2026
Diabetic Peripheral Neuropathy Mechanism Explorer
How might diabetes damage the small sensory fibers that supply the skin? This explorer brings together proposed mechanisms, the claims each one depends on, and the evidence behind our current judgments.
This site may be updated at any time. It is primarily a resource for knowledge organization used by the Center for the Study of Systems Biology at Georgia Tech, but has been made public in case other researchers or their AI agents find it useful as a starting point for DPN research.
Explore the mechanisms
The probability expresses confidence that the mechanism meets its stated causal criteria: by default, that selectively preventing it would avert at least 20% of five-year net terminal loss in a subgroup accounting for at least 10% of new DPN cases under reference care. IT IS NOT AN EFFECT SIZE.
(Think of it like a Polymarket price for if you were wagering whether the mechanism would meet that criteria in an ideal-world experiment)
All mechanisms
Glucose chemistry and exposure
| 01 | Polyol metabolismGlucose chemistry and exposure | 21.1% | 2.3% | 55.2% |
| 02 | Glucosamine and hexosamine stressGlucose chemistry and exposure | 5.4% | 0.13% | 38.1% |
| 03 | Extracellular matrix glycationGlucose chemistry and exposure | 15.5% | 0.82% | 55.2% |
| 04 | RAGE signalingGlucose chemistry and exposure | 9.4% | 0.3% | 43.2% |
| 05 | Methylglyoxal and carbonyl stressGlucose chemistry and exposure | 10.2% | 0.53% | 45.5% |
| 06 | Glucose overload and mitochondrial superoxideGlucose chemistry and exposure | 4.5% | 0.06% | 37.6% |
| 40 | Persistent regulatory memoryAfter exposure improvesGlucose chemistry and exposure | 3.3% | 0.09% | 30.6% |
| 42 | Glycemic variabilityGlucose chemistry and exposure | 11.5% | 0.72% | 45.4% |
Lipids and trophic support
| 08 | Fatty-acid deliveryLipids and trophic support | 12.4% | 0.41% | 55.8% |
| 09 | Oxidized LDLLipids and trophic support | 4.5% | 0.06% | 41.8% |
| 10 | DeoxysphingolipidsLipids and trophic support | 19.2% | 0.95% | 65.6% |
| 11 | Canonical ceramidesLipids and trophic support | 10.8% | 0.38% | 55.3% |
| 12 | Insulin and IGF supportLipids and trophic support | 15.2% | 0.68% | 58.5% |
| 13 | C-peptide deficiencyType 1 diabetesLipids and trophic support | 18.6% | 1.4% | 64% |
| 14 | NGF and TrkA supportLipids and trophic support | 16.1% | 0.75% | 61.8% |
| 43 | Protective lipid deficiencyLipids and trophic support | 11.6% | 0.66% | 43.4% |
| 45 | Amylin aggregationLipids and trophic support | 20.3% | 1% | 55.1% |
Blood supply, supporting cells, and repair
| 15 | Microvascular oxygen and fuel supplyBlood supply, supporting cells, and repair | 15.4% | 0.47% | 65.8% |
| 16 | Vascular PKC signalingBlood supply, supporting cells, and repair | 5.1% | 0.02% | 47.5% |
| 17 | Schwann-cell metabolic supportBlood supply, supporting cells, and repair | 13.2% | 0.36% | 62.3% |
| 18 | Glial mitochondrial transferBlood supply, supporting cells, and repair | 7.9% | 0.09% | 52.3% |
| 19 | TNF and TLR4 inflammationBlood supply, supporting cells, and repair | 19.2% | 0.81% | 69.3% |
| 20 | Protective macrophage functionBlood supply, supporting cells, and repair | 7.9% | 0.19% | 52% |
| 22 | Complement-mediated injuryBlood supply, supporting cells, and repair | 8.4% | 0.14% | 55.8% |
| 32 | The skin repair environmentBlood supply, supporting cells, and repair | 16% | 0.84% | 62.1% |
| 33 | Senescence-like cell statesBlood supply, supporting cells, and repair | 9.8% | 0.13% | 62.3% |
| 34 | Microbiome-derived exposuresBlood supply, supporting cells, and repair | 8% | 0.12% | 58.9% |
| 36 | Compression and mechanical injuryBlood supply, supporting cells, and repair | 6.5% | 0.06% | 52.3% |
| 44 | Intrinsic limits on axon regrowthRepair in established DPNBlood supply, supporting cells, and repair | 19% | 1.6% | 55.3% |
Cell maintenance and injury
| 07 | Insufficient axonal energyCell maintenance and injury | 33.8% | 4.1% | 77.2% |
| 21 | Inflammasomes and pyroptosisCell maintenance and injury | 6.3% | 0.08% | 55.8% |
| 23 | Endoplasmic reticulum stressCell maintenance and injury | 16.3% | 0.63% | 65.4% |
| 24 | Autophagy and mitophagyCell maintenance and injury | 10.7% | 0.34% | 55.3% |
| 25 | Mitochondrial dynamicsCell maintenance and injury | 16.3% | 0.63% | 62% |
| 26 | Axonal transportCell maintenance and injury | 14.3% | 0.37% | 62.3% |
| 27 | SARM1 axon destructionCell maintenance and injury | 36% | 2.5% | 77.2% |
| 28 | PARP and NAD depletionCell maintenance and injury | 23.9% | 1.5% | 65.4% |
| 29 | Ferroptotic injuryCell maintenance and injury | 7.6% | 0.09% | 47.1% |
| 30 | Sensory-neuron cell-body apoptosisCell maintenance and injury | 8.3% | 0.13% | 51.8% |
| 31 | Excitability and cation loadingCell maintenance and injury | 13.7% | 0.47% | 62% |
| 39 | Oxidative and nitrosative injuryCell maintenance and injury | 37.6% | 6.1% | 72.9% |
Treatment and comorbidity exposures
| 35 | Rapid glycemic correctionPost-correction neuropathy · Six monthsTreatment and comorbidity exposures | 16% | 0.39% | 62.1% |
| 37 | Metformin-associated B12 deficiencyLong-term metformin · Onset or progressionTreatment and comorbidity exposures | 18.5% | 0.54% | 68.6% |
| 38 | Kidney failure and uremic exposureAdvanced kidney disease · Onset or progressionTreatment and comorbidity exposures | 23.9% | 0.68% | 68.6% |
| 41 | Hypoglycemic energy failureDeep or sustained hypoglycemiaTreatment and comorbidity exposures | 18.2% | 1.4% | 51.7% |
For agents
Start with the JSON index, then read a report’s complete Markdown or structured claims. The full causal proposition, evidence, and qualifications are preserved alongside the concise reading view. All files are directly accessible without JavaScript.
How to cite this
Edelman, Brice, and Jeffrey Skolnick (2026). Diabetic Peripheral Neuropathy Mechanism Explorer. Snapshot 14 September 2026. Page permalink.
Include your access date when citing this evolving resource. BibTeX for the collection. For a study’s findings, also cite the original paper linked in the report.