Circulating proteomic markers are associated with measures of small and large fiber neuropathy and symptoms in type 2 diabetes.

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.