Abstract：
Diabetes mellitus, a metabolic condition affecting around 537 million individuals worldwide, poses significant challenges, particularly among the elderly population. The etiopathogenesis of type 2 diabetes (T2D) depends on a combination of the effects driven by advancing age, genetic background, and lifestyle habits, e.g. overnutrition. These factors influence the development of T2D differently in men and women, with an obvious sexual dimorphism possibly underlying the diverse clinical features of the disease in different sexes. More recently, environmental pollution, estimated to cause 9 million deaths every year, is emerging as a novel risk factor for the development of T2D. Indeed, exposure to atmospheric pollutants such as PM2.5, O3, NO2, and Persistent Organic Pollutants (POP)s, along with their combination and bioaccumulation, is associated with the development of T2D and obesity, with a 15 % excess risk in case of exposure to very high levels of PM2.5. Similar data are available for plasticizer molecules, e.g. bisphenol A and phthalates, emerging endocrine-disrupting chemicals. Even though causality is still debated at this stage, preclinical evidence sustains the ability of multiple pollutants to affect pancreatic function, promote insulin resistance, and alter lipid metabolism, possibly contributing to T2D onset and progression. In addition, preclinical findings suggest a possible role also for plastic itself in the development of T2D. Indeed, pioneeristic studies evidenced that micro- or nanoplastics (MNP)s, particles in the micro- or nano- range, promote cellular damage, senescence, inflammation, and metabolic disturbances, leading to insulin resistance and impaired glucose metabolism in animal and/or in vitro models. Here we synthesize recent knowledge relative to the association between air-related or plastic-derived pollutants and the incidence of T2D, discussing also the possible mechanistic links suggested by the available literature. We then anticipate the need for future studies in the field of candidate therapeutic strategies limiting pollution-induced damage in preclinical models, such as SGLT-2 inhibitors. We finally postulate that future guidelines for T2D prevention should consider pollution and sex an additional risk factors to limit the diabetes pandemic.
摘要：
糖尿病,一种影响全球约5.37亿人的代谢疾病，带来重大挑战，尤其是老年人。2型糖尿病（T2D）的病因取决于年龄增长所驱动的影响的组合，遗传背景,和生活习惯，例如营养过剩。这些因素对男性和女性T2D的发展有不同的影响，具有明显的性二态性，可能是该疾病在不同性别中的不同临床特征的基础。最近,环境污染,估计每年造成900万人死亡，正在成为T2D发展的新风险因素。的确,暴露于大气污染物，如PM2.5、O3、NO2和持久性有机污染物(POP)，随着它们的结合和生物积累，与T2D和肥胖的发展有关，在暴露于非常高水平的PM2.5的情况下，有15%的额外风险。增塑剂分子也有类似的数据，例如双酚A和邻苯二甲酸酯，新兴的内分泌干扰化学物质。尽管因果关系在这个阶段仍然存在争议，临床前证据维持多种污染物影响胰腺功能的能力，促进胰岛素抵抗，改变脂质代谢，可能有助于T2D的发病和进展。此外,临床前研究结果表明，塑料本身在T2D的发展中也可能发挥作用。的确,开创性研究证明，微米或纳米塑料(MNP)，微米或纳米范围的颗粒，促进细胞损伤，衰老，炎症,和代谢紊乱，在动物和/或体外模型中导致胰岛素抵抗和葡萄糖代谢受损。在这里，我们综合了有关空气相关或塑料衍生污染物与T2D发病率之间关联的最新知识，还讨论了现有文献提出的可能的机械联系。然后，我们预计在临床前模型中限制污染引起的损害的候选治疗策略领域的未来研究的需要。如SGLT-2抑制剂。我们最后假设，未来的T2D预防指南应该考虑污染和性别作为限制糖尿病流行的额外风险因素。
