Intersecting Molecular Pathways in Cardiovascular Disease and Diabetes Mellitus: Emerging Roles of Inflammation and Therapeutics

心血管疾病和糖尿病中交叉的分子通路:炎症和治疗的新兴作用

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Abstract

Diabetes mellitus (DM) and cardiovascular diseases (CVD) remain leading contributors to global morbidity and mortality, imposing a substantial burden on healthcare systems worldwide. The pathophysiological mechanisms underlying these conditions are complex and closely interconnected, with chronic low-grade inflammation, oxidative stress, endothelial dysfunction, insulin resistance and dysregulated lipid metabolism serving as pivotal shared pathways. Persistent hyperglycaemia and metabolic imbalance in DM accelerate vascular injury and atherosclerotic progression, thereby significantly increasing cardiovascular risk. Consequently, therapeutic strategies that concurrently target both metabolic and cardiovascular dysfunction may offer meaningful clinical advantages and improved long-term outcomes. In recent years, novel antidiabetic agents such as sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated not only glycaemic control but also substantial cardiovascular protection, including reductions in major adverse cardiovascular events, heart failure hospitalisations and renal disease progression. These pleiotropic effects extend beyond glucose lowering and involve modulation of inflammatory pathways, improvement of endothelial function, attenuation of oxidative stress and favourable haemodynamic changes. Additionally, emerging evidence highlights the role of the gut microbiota as a critical mediator in the bidirectional relationship between DM and CVD. Alterations in microbial composition and diversity, collectively termed dysbiosis, have been associated with systemic inflammation, impaired metabolic homoeostasis, increased intestinal permeability and the production of pro-atherogenic metabolites such as trimethylamine N-oxide. Understanding these microbiome-related mechanisms may open new avenues for preventive and therapeutic interventions targeting the gut-metabolic-cardiovascular axis. This narrative review provides an updated and comprehensive overview of the molecular and cellular mechanisms linking DM and CVD, with particular emphasis on inflammatory signalling, metabolic dysregulation and the emerging influence of the gut microbiome in their shared pathogenesis and therapeutic modulation.

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