Endocan, miR-221 predict development of diabetic peripheral neuropathy

Endocan and miR-221 expression levels are significantly associated with development of neuropathy in patients with diabetes, indicating their potential role as biomarkers to diagnose diabetic peripheral neuropathy (DPN) at an early stage before the development of clinical manifestations, reports a study presented at ATTD-Asia 2025.

“Currently, no reliable diagnostic tests are available for screening for DPN before appearance of clinical symptoms,” said lead study author Dr Rachita Nanda, All India Institute of Medical Science, Raipur, India.

“In view of the endoneurial dysfunction in DPN, endocan has been shown to be associated with diabetic complications, [while] miR-221 has been implicated in potentially influencing endothelial inflammation in vascular diseases,” she added.

Nanda and her team performed an observational analytical study in 49 patients with DPN and 48 without DPN (non-DPN group), who were recruited as per operational definitions and essential inclusion criteria. They collected and stored plasma at ‒80 °C, as well as analysed miR-221 using RT-PCR and endocan via ELISA. [ATTD-Asia 2025, abstract SOP026]

In comparisons of immunoinflammatory and endothelial markers, high-sensitivity C-reactive protein (hs-CRP; p=0.002) and endocan (p<0.001) were found to be significantly elevated in patients with DPN. These biomarkers also showed a positive association with DPN (r=0.242; p=0.017).

“Endocan levels are increased and could play functional role in endothelium-dependent injury like DPN through ICAM-1, VCAM-1, and E-selectin,” Nanda said.

“Considering this, endocan and a combination of these biomarkers might be suitable candidates for early identification of the risk of developing complications such as peripheral neuropathy in diabetes patients,” she added.

Predictor

On the other hand, the median fold change expression of miR-221 was significantly higher in the DPN than the non-DPN group (5.9199 vs 0.9491; p<0.001). Likewise, miR-221 showed a positive association with hs-CRP (p=0.002) and endocan (p=0.027).

Furthermore, the regression coefficient for miR-221 was positive and significant (b=0.69559; SE=0.165; p<0.001), indicating its potential role as a predictor of DPN development.

“The odds ratio [also] indicates that for every unit increase of this predictor, the odds of developing DPN increases by a factor 2,” Nanda said.

“The target prediction and interaction analysis suggest a plausible mechanistic role for miR-221 in the development of DPN,” she added.

DPN pathogenesis

Nanda and colleagues also identified several genes (ie, FOXO3, FOS, and ESR1) that play major roles in oxidative stress response, apoptosis regulation, and inflammatory signalling, processes that are critical to the pathogenesis of DPN.

“The PI3K/AKT pathway, also highlighted through involvement of PTEN and FOXO3, is particularly important in neuronal regeneration and insulin signalling, both of which are impaired in diabetes [patients],” Nanda said.

“Since miR-221 contributes to the pathophysiology of DPN by modulating interconnected gene networks involved in inflammation, oxidative damage, vascular impairment, and neuronal survival, this highlights miR-221 as a potential biomarker for early detection of diabetic neuropathy,” she added.