Molecular biomarkers in diabetes-related neurological complications: current evidence and translational challenges.

Abstract

Diabetes mellitus is increasingly recognized as a systemic disorder associated with a broad spectrum of neurological complications, including diabetic peripheral neuropathy, autonomic neuropathy, cerebrovascular disease, cognitive impairment, and neurodegenerative disorders. Because neurological injury may develop before the onset of overt clinical manifestations, the identification of reliable biomarkers for early risk assessment remains an important challenge in diabetes care. This narrative review summarizes current evidence regarding molecular biomarkers implicated in diabetes-related neurological complications. A literature search was conducted using major biomedical databases, with emphasis on human studies, systematic reviews, prospective cohorts, and clinically relevant translational research. Biomarker categories reviewed include inflammatory mediators, oxidative stress markers, advanced glycation end-products, neuronal injury proteins, metabolomic signatures, circulating microRNAs, extracellular vesicles, and multi-omics approaches. Current evidence suggests that several biomarkers are associated with neurological injury and adverse neurological outcomes in patients with diabetes. However, the strength of evidence varies substantially across biomarker classes. While some biomarkers demonstrate biological plausibility and consistent associations with disease burden, most remain at an exploratory stage and lack sufficient prospective validation for routine clinical implementation. Major barriers include study heterogeneity, assay variability, limited reproducibility, uncertainty regarding incremental predictive value, and insufficient evaluation in diabetes-specific populations. Future research should focus on rigorous validation of candidate biomarkers, standardization of analytical methods, and assessment of their added value beyond established clinical risk factors. The integration of molecular biomarkers with clinical variables, neuroimaging findings, and advanced analytical approaches may contribute to future risk stratification strategies; however, substantial validation is required before clinical implementation can be considered.