Circulating Inflammation-Related Proteins Linked to Corneal Neuroimmune Measures, Neuropathy Deficits, and Symptoms in Type 2 Diabetes.

OBJECTIVE

Systemic inflammation plays a key role in diabetic peripheral neuropathy (DPN). This exploratory study investigated circulating inflammation-related proteins associated with corneal neuroimmune measures, neuropathic deficits, and symptoms in patients 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 inflammation panel.

RESULTS

A total of 30 proteins were associated with neuropathy deficits and corneal DCD. Corneal nerve measures showed positive associations with two chemokines, four epithelial-barrier cytokines, and two growth-related mediators, and negative associations with three inflammatory cytokines/receptors, one anti-inflammatory cytokine/receptor, two immune-regulatory molecules, and one chemokine. VPT was positively associated with three inflammatory cytokines/receptors, while ESC showed negative associations with one metabolic-inflammatory enzyme, one chemokine, and one inflammatory receptor. Neuropathic symptoms based on DN4 were positively associated with one immune-regulatory molecule and negatively with one neurotrophic factor and one homeostatic cytokine. Corneal DCD showed positive associations with four inflammatory cytokines and one neurotrophic factor, and a negative association with one epithelial chemokine. Non-branching DCD was negatively associated with corneal nerve branch density (p ≤ 0.05).

CONCLUSIONS

Neuropathy deficits and corneal DCD in T2D are associated with distinct neuroimmune pathways.