Tracking the Biochemical Trail of Neuroinflammation in Diabetic Neuropathy: A Narrative Review

Diabetic Neuropathy (DN) is a long-term persistent neuro impairment associated with Type 2 Diabetes Mellitus (T2DM). DN develops when chronic hyperglycaemia damages peripheral and autonomic nerves, giving rise to a broad spectrum of clinical symptoms. The mechanism of DN is elaborate and multicomponent, mediated by persistent hyperglycaemia, lipid metabolic dysfunction, oxidative imbalance, impaired mitochondrial activity, and neuroinflammation, together giving rise to progressive peripheral nerve injury. Persistently raised glucose levels promote the accumulation of glycotoxins, leading to alteration in protein synthesis and function. Inflammatory mediators such as Interleukin-6 (IL-6), C-Reactive Protein (CRP), IL-18, IL-8, and Tumour Necrosis Factor alpha (TNF-α) further amplify nerve damage by activating Nuclear Factor kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Modern strategies for managing DN focus on glycaemic control, lifestyle modifications, and emerging treatments namely Sodium-Glucose Cotransporter 2 (SGLT2) targeting drugs and Glucagon-Like Peptide-1 (GLP-1) mimetic. Further the identification of biochemical markers and molecular targets may facilitate early diagnosis and enable more personalised interventions. Continued collaboration between basic science scientists and clinicians will be essential in translating biochemical insights into tangible benefits for individuals. Despite our growing knowledge of the complexity of DN has sustainably improved in prior years, yet such knowledge of biochemical aspects and earlier predictor of neuropathy associated with diabetes are not entirely clear. Hence, the present review tends to describe the present comprehension about biochemical aspects, mechanism of neurological progression, and interconnected pathways involved in DN.