Intradermal Advanced Glycation End-products Relate to Reduced Sciatic Nerve Structural Integrity in Type 2 Diabetes

Cardiovascular risk management is beneficial, but stringent glycemic control does not prevent the progression of distal sensorimotor polyneuropathy (DSPN). Persistent hyperglycemia-induced alterations and cardiovascular factors may contribute to diabetes-associated nerve damage. This study aimed to evaluate the correlation between skin auto-fluorescence (sAF), an indicator of dermal advanced glycation end-product (AGE) accumulations, cardiovascular risk, and changes in peripheral nerve integrity.

Sixty-two individuals with type 2 diabetes (T2D) (20 women and 42 men), including 29 diagnosed with DSPN (7 women and 22 men), and 10 healthy controls (HC) underwent diffusion tensor MR imaging of the sciatic nerve to assess fractional anisotropy (FA), an indicator of nerve structural integrity. sAF measurements were combined with clinical, serological, and electrophysiological evaluations. Arterial stiffness was assessed via pulse wave velocity (PWV).

sAF (HC 2.1 ± 0.25 AU, nDSPN 2.3 ± 0.47, DSPN 2.6 ± 0.43; p = 0.005) was higher in individuals with DSPN compared to HC (p = 0.010) and individuals without DSPN (p = 0.035). Within the group of T2D FA correlated negatively with sAF (r = -0.49, p < 0.001), PWV (r = -0.40, p = 0.009) and high-sensitivity troponin T (hsTNT), a marker of microvascular damage (r = -0.39, p < 0.001). In DSPN, sAF correlated positively with hsTNT (r = 0.58, p = 0.005) and with PWV (r = 0.52, p = 0.007), the sciatic nerve's FA correlated negatively with PWV (r = -0.47, p = 0.010).

This study is the first to show close correlations between reduced peripheral nerve integrity and both intradermal AGE deposition and arterial stiffness in individuals with T2D. These findings highlight a mechanistic link between glycation-related vascular injury and neuronal damage emphasizing the importance of cardiovascular risk management in preventing DSPN.