{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T01:04:53Z","timestamp":1778893493056,"version":"3.51.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019265","name":"Yuhan","doi-asserted-by":"publisher","award":["IIT-009"],"award-info":[{"award-number":["IIT-009"]}],"id":[{"id":"10.13039\/100019265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to \u03b2-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin\/ezetimibe combination treatment on T cell senescence markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg\/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin\/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (T<jats:sub>reg<\/jats:sub>) significantly decreased after intervention in the rosuvastatin\/ezetimibe group (\u22124.5 \u00b1 14.1% and \u22121.2 \u00b1 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 \u00b1 9.4% and 1.4 \u00b1 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, <jats:italic>p<\/jats:italic>=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, <jats:italic>p<\/jats:italic>=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (<jats:italic>p<\/jats:italic>=0.314) or LDL-C (<jats:italic>p<\/jats:italic>=0.592). Finally, the ratio of na\u00efve to memory CD8+ T cells increased in the rosuvastatin\/ezetimibe group (<jats:italic>p<\/jats:italic>=0.011), but not in the rosuvastatin group (<jats:italic>p<\/jats:italic>=0.339).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin\/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1336357","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T15:07:22Z","timestamp":1711120042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Distinct effects of rosuvastatin and rosuvastatin\/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial"],"prefix":"10.3389","volume":"15","author":[{"given":"Sang-Hyeon","family":"Ju","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joung Youl","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minchul","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Min","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yea Eun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyon-Seung","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyong Hye","family":"Joung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bon Jeong","family":"Ku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2015.19","article-title":"Type 2 diabetes mellitus","volume":"1","author":"Defronzo","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01655-5","article-title":"Type 2 diabetes","volume":"400","author":"Ahmad","year":"2022","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12944-021-01455-3","article-title":"Prevalence, awareness, treatment, and control of dyslipidemia among diabetes mellitus patients and predictors of optimal dyslipidemia control: results from the Korea National Health and Nutrition Examination Survey","volume":"20","author":"Kim","year":"2021","journal-title":"Lipids Health Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dc23-S010","article-title":"10. 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