Epidemiological and Mechanistic Links between PM2.5 Exposure and Type 2 Diabetes: Focus on the TRPV1 Receptor

Filippo Liviero^*Sofia Pavanello

• Universita degli Studi di Padova Dipartimento di Scienze Cardio-Toraco-Vascolari e Sanita pubblica, Padua, Italy

The growing global burden of type 2 diabetes (T2D) has prompted increasing attention to environmental factors that may contribute to its development. Among these, exposure to fine particulate matter (PM₂.₅) has emerged as a significant yet often overlooked risk factor. This systematic review, conducted according to PRISMA guidelines, provides a comprehensive appraisal of the epidemiological evidence and discusses mechanisms linking PM₂.₅ exposure to T2D onset and progression. Long-term exposure to PM₂.₅ is consistently associated with increased T2D risk, particularly among vulnerable groups such as individuals with obesity, metabolic syndrome, or advanced age. Evidence from animal models suggests acute exposure further exacerbates insulin resistance and impairs glucose metabolism. Mechanistic studies highlight roles of oxidative stress, systemic inflammation, endothelial dysfunction, and autonomic imbalance. Notably, recent findings implicate the transient receptor potential vanilloid 1 (TRPV1) in neurogenic inflammation and metabolic disruption, offering novel insights into how PM₂.₅ may influence glycemic control. Experimental evidence in humans indicates that traffic-related PM₂.₅, including diesel exhaust particulates (DEP), activates TRPV1, supporting its role as a molecular interface between environmental insults and metabolic disruption. Given its central role in neurogenic inflammation and metabolic regulation, TRPV1 has emerged as a promising therapeutic target. Preclinical studies have shown that pharmacological modulation of TRPV1 improves glucose tolerance and reduces inflammation. Currently, XEN-D0501, a TRPV1 antagonist, is undergoing clinical trials to assess its efficacy in regulating blood glucose and mitigating T2D-related inflammatory complications. Animal studies further demonstrate that PM₂.₅ exposure promotes visceral adiposity, impairs hepatic insulin signalling, and triggers tissue-specific inflammation. Despite the strength of the evidence, heterogeneity in exposure assessment, driven by spatial and temporal variations in PM₂.₅ sources and composition, and in study design, persists. Given the ubiquity of PM₂.₅ in urban environments, even modest increases in diabetes risk may translate into substantial public health burdens. Targeted policies to reduce air pollution, together with intensified research into biological susceptibility and prevention strategies, are essential. Addressing PM₂.₅ as a modifiable determinant of T2D represents a timely and actionable priority in environmental health.