Diabetic Neuropathy: Recent Diagnostic Advancements and Emerging Multimodal Therapeutic Strategies

Abstract: Diabetic Neuropathy (DN) is among the most prevalent and debilitating microvascular complications of diabetes mellitus, with Distal Symmetric Polyneuropathy (DPN) representing the predominant phenotype. Despite decades of research, diagnostic precision at early stages remains inadequate, and existing therapies are largely confined to symptomatic management rather than disease modification. This review critically evaluates recent advances in the mechanistic understanding, early diagnostic innovations, and evolving therapeutic paradigms of DN. Special emphasis is placed on emerging biomarkers, digital diagnostics, regenerative interventions, and neuromodulatory strategies that hold potential to transform clinical practice. A Literature survey was conducted across the PubMed, Scopus, and Web of Science databases to identify published studies. Eligible peer-reviewed articles included clinical trials, systematic reviews, meta-analyses, and translational research focusing on early detection modalities, molecular biomarker discovery, pharmacological interventions, and novel regenerative or neuromodulatory therapies. Key findings were synthesised and analysed narratively. Recent diagnostic innovations enable sensitive detection of small fibre neuropathy, often preceding overt clinical manifestations. On the therapeutic front, a multimodal strategy is gaining ground. Established pharmacological agents such as pregabalin and duloxetine remain central, but adjunctive interventions, including antioxidant-enriched nutritional strategies and neuromodulation techniques (e.g., transcutaneous electrical nerve stimulation, spinal cord stimulation), provide additional benefit. Regenerative approaches, notably stem cell therapy, exosome-based delivery, and CRISPR/Cas-mediated gene modulation, are emerging as promising avenues for reversing neuronal injury rather than merely alleviating symptoms. Advances in precision diagnostics and integrative therapeutics are redefining the clinical landscape of DN. Early identification through sensitive digital and molecular tools, combined with multimodal and regenerative treatment strategies, underscores a paradigm shift from reactive symptomatic care toward preventive neurology and personalised medicine. Harnessing these innovations may ultimately alter the trajectory of DN, reducing disability and improving long-term quality of life in patients with diabetes. DOI:10.2174/0125899775400471251205102738