Circulating proteomic markers are associated with measures of small and large fiber neuropathy and symptoms in type 2 diabetes
Journal of Diabetes and its Complications, 2026
Ponirakis G., Al-Janahi I., Elgassim E., Dalloul R., Petropoulos I., Gad H., Khan A., Zaghloul H., Ali H., Siddique M., Mohamed F., Ahmed L., Dakroury Y., El Shewehy A., Saeid R., Mahjoub F., Al-Noubi M., Sarwath H., Paul P., Kaul R., Salivon I., Zirie M., Al-Ansari Y., Atkin S., Schmidt F., Malik R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases Neurology | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
Aims
To explore associations between circulating proteomic pathways and structural, functional, and symptomatic measures of small- and large-fiber neuropathy and corneal immune activation in people with Type 2 diabetes (T2D).
Methods
Participants with T2D (n = 44) underwent assessment of corneal nerve morphology and dendritic cell density (DCD), vibration perception threshold (VPT), electrochemical skin conductance (ESC), DN4 questionnaire and profiling of 92 plasma proteins using the Olink® Neurology panel.
Results
Corneal nerve parameters correlated positively with axon-guidance proteins (NRP2, NBL1) and negatively with immune-adhesion proteins (ROBO2, Siglec-1). Higher VPT correlated with N-CDase and TMPRSS5, while lower ESC correlated with immune–vascular proteins (Galectin-8, CLEC1B, LAT, CLM-1). Higher DN4 scores correlated with adhesion molecules, neurotrophic receptors (GFRα1, GFRα3), and immune checkpoint regulators (CD200, JAM-B). DCD correlated with IL-12 and kynurenine pathway activation.
Conclusions
Structural and functional alterations and symptoms of neuropathy are related to proteins regulating axon guidance, metabolic, immune, and neurotrophic pathways in patients with T2D.