miRNAs 谱作为营养治疗预防 2 型糖尿病的生物标志物：来自 CORDIOPREV 研究。

MiRNAs profile as biomarkers of nutritional therapy for the prevention of type 2 diabetes mellitus: From the CORDIOPREV study.

机构信息

Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba. Córdoba. Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.

Biochemical Laboratory, Reina Sofia University Hospital, Córdoba, Spain.

出版信息

Clin Nutr. 2021 Mar;40(3):1028-1038. doi: 10.1016/j.clnu.2020.06.035. Epub 2020 Jul 15.

DOI:10.1016/j.clnu.2020.06.035

PMID:32723508

Abstract

BACKGROUND AND AIM

The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide. One of the first actions to reduce the risk of this disease is to implement healthy dietary models; however, no universal dietary strategies have so far been established. In addition, MicroRNAs (miRNAs) are emerging as new biomarkers to predict disease. We aimed to study whether miRNAs could be used to select the nutritional therapy to prevent T2DM development in patients with cardiovascular disease.

METHODS

All patients from the CORDIOPREV study without T2DM at baseline according to the American Diabetes Association (ADA) diagnostic criteria (n = 462) were included in the present study. Of them, after a median dietary intervention period of 60 months with two diets (Low fat or Mediterranean diets), 107 developed T2DM and 355 subjects did not develop the disease. The plasma levels of 24 miRNAs were measured at baseline by qRT-PCR. The risk of T2DM was evaluated by Cox regression analysis based on the plasma levels of the miRNAs at baseline and according to the dietary intervention. Finally, pathways analyses were carried out to identify target genes regulated by the miRNAs studied and cellular processes which could be associated with T2DM development.

RESULTS

Cox regression analyses showed that patients with low plasma levels of miR-145 at baseline showed a higher risk of developing T2DM after consumption of an LFHCC diet. In addition, patients with low levels of miR-29a, miR-28-3p and miR-126 and high plasma levels of miR-150 at baseline showed a higher risk of developing T2DM after consumption of the Med diet. Finally, pathways analysis showed an interaction of miR-126 and miR-29a in the modulation of FoxO, TNF-α, PI3K-AKT, p53 and mTOR signaling, associated with T2DM development.

CONCLUSION

Our results suggest that circulating miRNAs could be used in clinical practice as a new tool for selecting the most suitable diet to prevent type 2 diabetes mellitus development in patients with cardiovascular disease.

CLINICAL TRIALS NUMBER

NCT00924937.

摘要

背景和目的

2 型糖尿病（T2DM）的发病率在全球范围内有所增加。降低这种疾病风险的首要措施之一是实施健康的饮食模式；然而，到目前为止，还没有建立通用的饮食策略。此外，MicroRNAs（miRNAs）作为预测疾病的新生物标志物而出现。我们旨在研究 miRNA 是否可用于选择营养疗法，以预防心血管疾病患者 T2DM 的发生。

方法

根据美国糖尿病协会（ADA）的诊断标准，本研究纳入了 CORDIOPREV 研究中所有基线时无 T2DM 的患者（n=462）。在接受为期 60 个月的两种饮食（低脂或地中海饮食）的中位饮食干预后，107 例患者发生 T2DM，355 例患者未发生该疾病。基线时通过 qRT-PCR 测量了 24 种 miRNA 的血浆水平。基于基线时 miRNA 的血浆水平并根据饮食干预，使用 Cox 回归分析评估 T2DM 的风险。最后，进行通路分析以确定受研究 miRNA 调控的靶基因和可能与 T2DM 发生相关的细胞过程。

结果

Cox 回归分析显示，基线时血浆 miR-145 水平较低的患者在接受 LFHCC 饮食后发生 T2DM 的风险较高。此外，基线时 miR-29a、miR-28-3p 和 miR-126 水平较低且 miR-150 水平较高的患者在接受 Med 饮食后发生 T2DM 的风险较高。最后，通路分析显示 miR-126 和 miR-29a 相互作用，调节 FoxO、TNF-α、PI3K-AKT、p53 和 mTOR 信号通路，与 T2DM 的发生有关。