Objectives Herpes zoster (HZ) infection is associated with a higher risk of major adverse cardiovascular events (MACE), including stroke and coronary artery disease (CAD). Patients with diabetes are at an increased risk of MACE, highlighting the importance of studying this population to assess the potential protective effects of HZ vaccination. This study aims to investigate the risk of MACE after HZ vaccination in patients with diabetes. Design Retrospective cohort study. Setting Community-based population in the USA. Participants Using the TriNetX database, the study included 4.9 million patients with diabetes from 2006 to 2022. It established two cohorts: 68 178 patients in the HZ vaccination (comprising any HZ vaccine, Shingrix or Zostavax) and 4 835 246 patients in the no HZ vaccination group. After excluding patients with a history of MACE, immune disease and complications of HZ prior to the index date, the study cohort was reduced to 45 960 patients. Propensity score matching, accounting for age, sex, race, socio-economic status and disease comorbidities, was conducted to minimise study bias. Interventions HZ vaccination. Outcome measures MACE outcomes are defined as the first occurrence of CAD or stroke. Comparative risk analysis was conducted using HRs. Results Post matching, the mean patient age was 63.5 years, with 49.2% females. The incidence rate of MACE was lower among vaccinated patients compared with unvaccinated individuals, with an HR of 0.76 (0.72–0.79). For secondary endpoints, the HRs were 0.73 (0.69–0.78) for CAD, 0.79 (0.74–0.84) for stroke and 0.54 (0.52–0.57) for all-cause mortality. These protective effects remained consistent across different age groups, sexes and diabetes types, supporting the potential benefit of HZ vaccination in reducing cardiovascular risk. Conclusions HZ vaccination is associated with a lower risk of MACE in patients with diabetes. Further prospective studies are critically needed to confirm this finding.

Diabetic neuropathy (DN) is a type of sensory nerve damage that can occur in patients with diabetes. Although the understanding of pathophysiology is incomplete, DN is often associated with structural and functional alterations of the affected neurons. Among all possible causes of nerve damage, Schwann cells (SCs) are thought to play a key role in repairing peripheral nerve injury, suggesting that functional deficits occurring in SCs may potentially exhibit their pathogenic roles in DN. Therefore, elucidating the mechanisms that underlie this pathology can be used to develop novel therapeutic targets. In this regard, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently attracted great attention in ameliorating SCs’ dysfunction. However, the detailed mechanisms remain uncertain. In the present study, we investigated how GLP-1 RA Liraglutide protects against RSC96 SCs dysfunction through a diabetic condition mimicked by high glucose and high free fatty acid (FFA). Our results showed that high glucose and high FFAs reduced the viability of RSC96 SCs by up to 51%, whereas Liraglutide reduced oxidative stress by upregulating antioxidant enzymes, and thus protected cells from apoptosis. Liraglutide also inhibited NFκB-mediated inflammation, inducing SCs to switch from pro-inflammatory cytokine production to anti-inflammatory cytokine production. Moreover, Liraglutide upregulated the production of neurotrophic factors and myelination-related proteins, and these protective effects appear to be synergistically linked to insulin signaling. Taken together, our findings demonstrate that Liraglutide ameliorates diabetes-related SC dysfunction through the above-mentioned mechanisms, and suggest that modulating GLP-1 signaling in SCs may be a promising strategy against DN.