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Background <p>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.</p> Methods <p>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.</p> Results <p>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 &lt; 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 &lt; 0.001).</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月24日

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  • Miriam Longo,
  • Paola Caruso,
  • Maria Chiara Auriemma,
  • Antonietta Maio,
  • Irene Di Meo,
  • Lorenzo Scappaticcio,
  • Maria Ida Maiorino,
  • Giuseppe Bellastella,
  • Maria Rosaria Rizzo,
  • Giuseppe Paolisso,
  • Katherine Esposito

摘要

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.