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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.
- Source :
-
Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2024 Mar 22; Vol. 15, pp. 1336357. Date of Electronic Publication: 2024 Mar 22 (Print Publication: 2024). - Publication Year :
- 2024
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Abstract
- Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-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.<br />Methods: 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.<br />Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (T <subscript>reg</subscript> ) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p =0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p =0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c ( p =0.314) or LDL-C ( p =0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group ( p =0.011), but not in the rosuvastatin group ( p =0.339).<br />Conclusions: 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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2024 Ju, Lim, Song, Kim, Kang, Yi, Joung, Lee, Kim and Ku.)
- Subjects :
- Humans
Rosuvastatin Calcium therapeutic use
Ezetimibe therapeutic use
Cholesterol, LDL
Glycated Hemoglobin
Leukocytes, Mononuclear
Fluorobenzenes therapeutic use
Pyrimidines
Sulfonamides therapeutic use
Drug Therapy, Combination
Treatment Outcome
Inflammation drug therapy
T-Lymphocytes
Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
Anticholesteremic Agents therapeutic use
Diabetes Mellitus, Type 2 drug therapy
Hypercholesterolemia drug therapy
Azetidines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1664-2392
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Frontiers in endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 38586464
- Full Text :
- https://doi.org/10.3389/fendo.2024.1336357