Angiogenic T cells and cognitive function in older adults with type 2 diabetes treated with GLP-1 receptor agonists

Background: Older adults with type 2 diabetes mellitus (T2DM) are at high risk of both cardiovascular complications and cognitive decline, with major implications for independence and self-management. Endothelial dysfunction and impaired angiogenic capacity may play a key role. This study investigated the association between circulating angiogenic T cells (Tang cells) and cognitive function in older adults with T2DM and explored the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. Methods: A cross-sectional study was conducted on 154 T2DM patients aged 60-80 years, treated either with GLP-1 receptor agonist (GLP-1RA) plus metformin or metformin alone. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Circulating CD3+CD31+CXCR4+ Tang cells were quantified by flow cytometry. Propensity score matching was applied to control for age, body weight and HbA1c. Results: In the overall cohort, higher Tang cell levels were significantly associated with better cognitive performance (MoCA, r = 0.423; MMSE, r = 0.428; both P < 0.001). After matching, 35 patients in each treatment group were included in the comparative analysis. The GLP-1RA + MET group showed significantly higher circulating Tang cell levels than the MET group, both in absolute counts and as percentage of CD3+ T cells (P < 0.001). Conclusions: Circulating Tang cell levels are positively associated with cognitive function in older adults with T2DM. GLP-1RA therapy is associated with higher Tang cell levels compared with metformin alone, suggesting a potential association with mechanisms related to endothelial repair in diabetes-related cognitive impairment in older age.