Diabetic polyneuropathy
disease diseaseOn this page
Also known as polyneuropathy in diabetes
Summary
Diabetic polyneuropathy (MONDO:0001583) is a disease with 22 GWAS associations across 7 studies and 69 clinical trials. Top therapeutic interventions include botulinum toxin type a, capsaicin, and duloxetine. A subtype of diabetic neuropathy — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- GWAS associations: 22
- Clinical trials: 69
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | diabetic polyneuropathy |
| Mondo ID | MONDO:0001583 |
| DOID | DOID:12785 |
| ICD-11 | 1837670870 |
| SNOMED CT | 49455004 |
| UMLS | C0271680 |
| MedGen | 75763 |
| Is cancer (heuristic) | no |
Also known as: polyneuropathy in diabetes
Data availability: 22 GWAS associations (7 studies).
Disease family
This is a subtype of diabetic neuropathy. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › peripheral nervous system disorder › peripheral neuropathy › diabetic neuropathy › diabetic polyneuropathy
Related subtypes (1): diabetic autonomic neuropathy
Genetics & variants
GWAS landscape
22 GWAS associations across 7 studies. Top hits map to 8 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| rs7903146 | 2e-84 | TCF7L2 | C | 0.2 |
| rs62048402 | 4e-38 | FTO | G | 0.13 |
| rs1421085 | 2e-33 | FTO | T | 0.13 |
| rs6780171 | 1e-27 | IGF2BP2 | T | 0.12 |
| rs9854769 | 4e-22 | IGF2BP2 | A | 0.1 |
| rs10811662 | 8e-19 | CDKN2B-AS1 | G | 0.13 |
| rs10811660 | 4e-18 | CDKN2B-AS1 | G | 0.13 |
| rs2673142 | 1e-16 | NYAP2 - MIR5702 | G | 0.09 |
| rs1801214 | 4e-16 | WFS1 | C | 0.08 |
| rs1794269 | 9e-15 | HLA-DQB1 - MTCO3P1 | C | 0.08 |
| rs4234731 | 7e-14 | WFS1 | A | 0.08 |
| rs9348441 | 1e-13 | CDKAL1 | T | 0.08 |
| chr4:103220401 | 1e-12 | C | 0.09 | |
| chr18:57846077 | 3e-12 | C | 0.09 | |
| rs182533474 | 1e-11 | JAZF1 | C | 0.07 |
| chr10:94466495 | 2e-11 | G | 0.07 | |
| rs234864 | 2e-11 | KCNQ1 | G | 0.07 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90475686 | Verma A | 2024 | 18,533 | 421,371 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90475685 | Verma A | 2024 | 4,528 | 114,074 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90479890 | Verma A | 2024 | 4,528 | 114,074 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90477326 | Verma A | 2024 | 2,180 | 56,290 | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program. |
| GCST90079851 | Backman JD | 2021 | 538 | 387,392 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90083837 | Backman JD | 2021 | 538 | 387,392 | Exome sequencing and analysis of 454,787 UK Biobank participants. |
| GCST90435713 | Zhou W | 2018 | 354 | 388,756 | Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 16 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 17 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 9 |
| intergenic_variant | 4 |
| unknown | 3 |
| missense_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| rs7903146 | 10 | 112998590 | C>G,T | 0.292 | intron_variant | TCF7L2 | 2e-84 | Tier 4: intronic/intergenic |
| rs62048402 | 16 | 53769311 | G>A,T | 0.403 | intron_variant | FTO | 4e-38 | Tier 4: intronic/intergenic |
| rs1421085 | 16 | 53767042 | T>C | 0.334 | intron_variant | FTO | 2e-33 | Tier 4: intronic/intergenic |
| rs6780171 | 3 | 185785668 | T>A | 0.309 | intron_variant | IGF2BP2 | 1e-27 | Tier 4: intronic/intergenic |
| rs9854769 | 3 | 185803160 | A>G | 0.398 | intron_variant | IGF2BP2 | 4e-22 | Tier 4: intronic/intergenic |
| rs10811662 | 9 | 22134254 | G>A,C | 0.173 | intergenic_variant | CDKN2B-AS1 | 8e-19 | Tier 4: intronic/intergenic |
| rs10811660 | 9 | 22134069 | G>A,C,T | 0.148 | intergenic_variant | CDKN2B-AS1 | 4e-18 | Tier 4: intronic/intergenic |
| rs2673142 | 2 | 226291929 | G>A,C,T | 0.375 | intergenic_variant | NYAP2 - MIR5702 | 1e-16 | Tier 4: intronic/intergenic |
| rs1801214 | 4 | 6301295 | C>A,G,T | 0.397 | missense_variant | WFS1 | 4e-16 | Tier 1: coding |
| rs1794269 | 6 | 32706117 | C>G,T | 0.372 | intergenic_variant | HLA-DQB1 - MTCO3P1 | 9e-15 | Tier 4: intronic/intergenic |
| rs4234731 | 4 | 6298187 | A>C,G,T | 0.389 | intron_variant | WFS1 | 7e-14 | Tier 4: intronic/intergenic |
| rs9348441 | 6 | 20680447 | T>A | 0.263 | intron_variant | CDKAL1 | 1e-13 | Tier 4: intronic/intergenic |
| chr4:103220401 | 0.231 | 1e-12 | Tier 4: intronic/intergenic | |||||
| chr18:57846077 | 0.214 | 3e-12 | Tier 4: intronic/intergenic | |||||
| rs182533474 | 7 | 28175045 | C>A | 0.414 | intron_variant | JAZF1 | 1e-11 | Tier 4: intronic/intergenic |
| chr10:94466495 | 0.401 | 2e-11 | Tier 4: intronic/intergenic | |||||
| rs234864 | 11 | 2836067 | G>A | 0.46 | intron_variant | KCNQ1 | 2e-11 | Tier 4: intronic/intergenic |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
No druggable-target or therapeutic data for this disease’s cohort.
Clinical trials & evidence
Clinical trials
Clinical trials: 69.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 38 |
| PHASE2 | 18 |
| PHASE3 | 6 |
| PHASE2/PHASE3 | 3 |
| PHASE4 | 2 |
| PHASE1/PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01116531 | PHASE4 | WITHDRAWN | Efficacy, Safety, Tolerability and Pharmacokinetics of Concomitant Administration of Tramadol With Duloxetine or Pregabalin |
| NCT01251211 | PHASE4 | COMPLETED | Botulinum Toxin in Peripheral Neuropathic Pain |
| NCT07475065 | PHASE2/PHASE3 | NOT_YET_RECRUITING | The Effect of Oral DLBS1033 in Patients With Diabetic Polyneuropathy |
| NCT00289497 | PHASE2/PHASE3 | COMPLETED | TempTouch IR Thermometry & Diabetic Patient Self-Care |
| NCT00328601 | PHASE3 | COMPLETED | Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Symptomatic Diabetic Neuropathy (SYDNEY 2) |
| NCT00977483 | PHASE3 | COMPLETED | Assessment of Efficacy and Safety of Thioctic Acid in the Oral Treatment of Diabetic Polyneuropathy (Stage 1 or 2) |
| NCT00993070 | PHASE2/PHASE3 | COMPLETED | Efficacy and Safety Study of Topical Capsaicin in Painful Diabetic Neuropathy |
| NCT01063868 | PHASE3 | TERMINATED | A Long-term Safety Study With Tapentadol ER and Oxycodone CR in Patients With Moderate to Severe Pain Due to Chronic, Painful Diabetic Peripheral Neuropathy (DPN) |
| NCT01465620 | PHASE3 | COMPLETED | Dietetic and Hygiene Measures in Metabolic Neuropathies: the Neurodiet Study |
| NCT06071975 | PHASE3 | UNKNOWN | Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy |
| NCT06072573 | PHASE3 | UNKNOWN | Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy |
| NCT06568185 | PHASE2 | RECRUITING | The Effect of Alpha Lipoid Acid and Vitamin B Preparation on Diabetic Polyneuropathy in Type 2 Diabetes Mellitus Patient |
| NCT07000214 | PHASE2 | RECRUITING | Peripheral Magnetic Stimulation With Balance Training to Decrease Fall Risks in Diabetic Polyneuropathy |
| NCT00043797 | PHASE2 | UNKNOWN | Lidorestat (IDD 676) for the Treatment of Diabetic Neuropathy |
| NCT00278980 | PHASE2 | COMPLETED | Effect of C-Peptide on Diabetic Peripheral Neuropathy |
| NCT00307749 | PHASE2 | COMPLETED | Safety and Efficacy of MCC-257 in the Treatment of Diabetic Polyneuropathy |
| NCT00406458 | PHASE2 | COMPLETED | Clinical Trial of SB-509 in Subjects With Diabetic Neuropathy |
| NCT00476931 | PHASE2 | COMPLETED | Clinical Trial of SB-509 in Subjects With Diabetic Neuropathy |
| NCT00501202 | PHASE2 | COMPLETED | Study for Safety and Effectiveness of RWJ-333369 (Carsibamate) for the Treatment of Diabetic Peripheral Neuropathy (DPN). |
| NCT00507936 | PHASE2 | COMPLETED | Safety and Efficacy Study in Subjects With Diabetic Neuropathic Pain |
| NCT00665145 | PHASE2 | COMPLETED | Stem Cell Mobilization in Diabetic Neuropathy Subjects Receiving SB-509 |
| NCT00878293 | PHASE2 | COMPLETED | Painful Diabetic Polyneuropathy Trial With a New Centrally Acting Analgesic |
| NCT01079325 | PHASE2 | COMPLETED | Clinical Trial of SB-509 in Subjects With Diabetic Neuropathy |
| NCT01175928 | PHASE1/PHASE2 | UNKNOWN | Pneumatic Medicine: A Transformative Treatment for Diabetic Peripheral Neuropathy |
| NCT01607684 | PHASE2 | COMPLETED | Pilot Study to Evaluate Magnetic Marker Imaging on Diabetic Polyneuropathy and Gastroparesis |
| NCT01622777 | PHASE2 | COMPLETED | The Effect of Rosuvastatin in Diabetic Polyneuropathy: A Phase IIa Randomized Double-blind Placebo-controlled Study |
| NCT02129231 | PHASE2 | COMPLETED | Statins for Oxidative Stress and Mitochondrial Function in Diabetic Polyneuropathy |
| NCT02597257 | PHASE2 | UNKNOWN | Efficacy and Safety of Lidocaine Infusion Treatment in Management of Neuropathic Pain |
| NCT05937152 | PHASE2 | WITHDRAWN | A Study of CGRP Monoclonal Antibody to Treat Diabetic Neuropathy |
| NCT07148804 | PHASE2 | COMPLETED | A Double-Blind, Placebo-Controlled Study of Fermented Deglycyrrhizinated Licorice Extract |
| NCT06904417 | PHASE1 | ENROLLING_BY_INVITATION | Effect of Feldenkrais Method in Enhancing Postural Control for Patients with Diabetic Polyneuropathy |
| NCT03767478 | Not specified | ACTIVE_NOT_RECRUITING | Neuromuscular Electrical Stimulation For The Treatment of Diabetic Neuropathy |
| NCT05521737 | Not specified | RECRUITING | Effect of Electroacupuncture on Sensitive Symptoms of Distal Diabetic Peripheral Neuropathy |
| NCT06040567 | Not specified | RECRUITING | Polyneuropathy, Impairments and Physical Activity - The PolyImPAct Study |
| NCT06124586 | Not specified | RECRUITING | Early Percutaneous Transluminal Angioplasty in Diabetic Foot Syndrome (PTA-DFS) |
| NCT06514846 | Not specified | RECRUITING | Utilizing the Michigan Neuropathy Screening Instrument for Early Detection of Diabetic Neuropathy |
| NCT06739135 | Not specified | RECRUITING | Driving with Neuropathy |
| NCT06778005 | Not specified | RECRUITING | Investigation of Ultrasonographic Measurements of Lower Extremity Nerves in Type 2 Diabetes Patients With Peripheral Polyneuropathy |
| NCT07248631 | Not specified | RECRUITING | Combined Effects of Foot-Ankle Therapeutic Exercises and Mindful Walking in Patients With Diabetic Polyneuropathy |
| NCT07369297 | Not specified | NOT_YET_RECRUITING | PULP SENSIBILITY AND MASSETER INHIBITORY REFLEX IN DIABETIC POLYNEUROPATHY |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| BOTULINUM TOXIN TYPE A | 4 | 1 |
| CAPSAICIN | 4 | 1 |
| DULOXETINE | 4 | 1 |
| EPTINEZUMAB | 4 | 1 |
| LIDOCAINE HYDROCHLORIDE | 4 | 1 |
| MAGNESIUM OXIDE | 4 | 1 |
| PREGABALIN | 4 | 1 |
| TRAMADOL | 4 | 1 |
| LIPOIC ACID, ALPHA | 3 | 4 |
| CARISBAMATE | 3 | 1 |
| CEBRANOPADOL | 3 | 1 |
| ZUCAPSAICIN | 3 | 1 |
| COLENEURAMIDE | 2 | 1 |
| HUMAN C-PEPTIDE | 2 | 1 |
| ISOXAFLUTOLE | 2 | 1 |
| SOFINICLINE | 2 | 1 |
| CHEMBL1234071 | 0 | 2 |
| THIOCTIC ACID | 0 | 2 |
| CHEMBL4059722 | 0 | 1 |
| CHEMBL541521 | 0 | 1 |
| (R)-DULOXETINE | 0 | 1 |
| (R,R)-TRAMADOL | 0 | 1 |