Inflammation, oxidative stress, matrix metalloproteinases and DNA damage in diabetic polyneuropathy and neuropathic...

Diabetic polyneuropathy is one of the most common complications of type 2 diabetes mellitus (DM) and represents a major cause of morbidity and impaired quality of life. This study aimed to investigate the associations between inflammation, oxidative stress, matrix metalloproteinases (MMPs), DNA damage, and the presence of distal symmetric diabetic polyneuropathy (DPNP) and diabetic neuropathic pain (DNP).

A total of 108 patients with Type 2 DM and 42 healthy controls (HC) were enrolled prospectively. Diabetic patients were classified as having DPNP based on clinical and electrodiagnostic findings. DNP was evaluated using the Douleur Neuropathique 4 (DN4) questionnaire. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), MMP-2, MMP-9, MMP-10, Oxidative Stress Index (OSI), and DNA damage were measured.

Levels of IL-6, TNF-α, IL-1β, MMP-9, MMP-10, OSI, and DNA damage were significantly higher in diabetic patients compared with HC (p < 0.001 for all). Among diabetic patients, all biomarkers except MMP-2 were significantly elevated in those with DPNP and DNP (p < 0.001 for all). In diabetic patients, the levels of IL-6, TNF-α and IL-1β showed strong correlations with each other and with MMP-9 and OSI levels. Multivariable analysis demonstrated that the presence of DPNP was independently associated with increased levels of MMP-9, MMP-10, and OSI whereas the presence of DNP was independently associated with increased OSI levels.

Inflammation, oxidative stress, and matrix metalloproteinase activation are strongly associated with DPNP and DNP in patients with Type 2 DM. Correlations among these parameters are consistent with the presence of an interconnected pathophysiological network. These findings provide additional insight into the complex pathophysiology of diabetic neuropathy.