Introduction: Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Social Isolation (SI) has been identified as a modifiable risk factor for stroke and a contributing factor to poorer functional outcomes. SI has been increasingly recognized as a significant stressor that can impact metabolic health through various biological mechanisms. The relationship between SI and metabolic dysfunction is complex and involves interactions among the neuroendocrine, immune, and metabolic systems. However, studies investigating the role of SI in the development of host metabolic dysfunction in the context of stroke are limited. Hypothesis: Isolation alters metabolic pathways after stroke. Methods: We analyzed untargeted serum metabolic profiles of AIS patients (N=100) 24 hours after last known well, along with questionnaires regarding SI and loneliness, to assess metabolic differences between socially isolated and socially interactive individuals. Samples were collected from patients ranging from 29 to 89 years old, with 66 males and 34 females. SI was measured via the Lubben Social Network Scale collected from patients during their hospitalization. Results: We found that there is a significant correlation between Lubben Social Network score and alterations in genes related to insulin resistance and glycolysis (FDR adjusted p <0.05). Interestingly, acetyl-CoA carboxylase and glycogen phosphorylase were significantly downregulated in patients with lower Lubben Social Network scores, suggesting isolated individuals have lower rates of metabolic turnover. Our results also demonstrated that suppressor of cytokine signaling (SOCS) was shown to be upregulated with an increased Lubben Social Network scores, suggesting that SI patients have systemic cytokine signaling and inflammation compared to non-SI stroke patients. Conclusion: In summary, systemic alterations in metabolic activity are pronounced after stroke, correlate with SI status pre-injury and functional outcome post-injury, and have the potential to directly affect cellular function. We demonstrated that socially isolated individuals are more likely to have metabolic dysfunction, which is a significant risk factor for post stroke disability and recurrent stroke. These metabolic factors should be analyzed additionally through the lens of sex, race, and other social determinants of health that affect stroke severity and functional outcomes.

Abstract Background Accumulating evidence shows that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiovascular outcomes. However, this favorable effect is unclear for newly atrial fibrillation (AF) development compared to other anti-diabetic drugs. Purpose We investigated the association of SGLT-2 inhibitor for newly AF development compared to dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes. Methods Using the Korean National Health Insurance Service database, among 2,160,911 type 2 diabetes patients (age ≥20 years) between 1 May 2016 and 31 December 2018, we studied 42,806 patients with SGLT-2 inhibitors and 448,715 patients with DPP-4 inhibitors who had not prior AF diagnosis. Propensity score-matching (1:1 ratio) was used to correct for differences between the groups. Results During a median follow-up of 1.3 years, after propensity score matching, compared with patients with DPP-4 inhibitors (n=42,786), patients with SGLT-2 inhibitors (n=42,786) have shown lower incidence and risk of AF (2.7 and 3.3 per 1000 person-years; hazard ratio 0.73, 95% confidence interval 0.55-0.97; p=0.028) aand an absolute rate difference of −0.7 [95% confidence interval (CI) −1.3 to −0.1, p=0.034] per 1000 person-years by on-treatment analysis. In intention-to-treat analysis, these results were consistent (2.6 and 3.2 per 1000 person-years; hazard ratio 0.83, 95% confidence interval 0.66-1.03; p=0.092) with an absolute rate difference of −0.5 [95% confidence interval (CI) −1.2 to −0.1, p=0.093] per 1000 person-years . In subgroup analysis, SGLT-2 inhibitors were associated with lower risks of AF in heart failure compared to their counterparts in intention-to-treat analysis (p for interaction=0.036). Conclusion Based on this nationwide cohort of type 2 diabetes patients treated with SGLT-2 inhibitors or DPP-4 inhibitors, SGLT-2 inhibitors were associated with protection against newly AF development after adjusting for clinical confounders.Incidence rates and adjusted HR