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1 型糖尿病长期幸存者白细胞端粒长度缩短和 SIRT1 基因表达降低:Dialong 子研究。

Reduced leukocyte telomere lengths and sirtuin 1 gene expression in long-term survivors of type 1 diabetes: A Dialong substudy.

机构信息

Department of Cardiology, Center for Clinical Heart Research, Oslo University Hospital, Ullevål, Norway.

Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

出版信息

J Diabetes Investig. 2021 Jul;12(7):1183-1192. doi: 10.1111/jdi.13470. Epub 2020 Dec 30.

Abstract

AIMS/INTRODUCTION: The shortening of leukocyte telomere length with age has been associated with coronary disease, whereas the association with type 1 diabetes is unclear. We aimed to explore telomere lengths in diabetes patients with regard to coronary artery disease, compared with healthy controls. The longevity factors sirtuin 1 and growth-differentiating factor 11 were investigated accordingly.

MATERIALS AND METHODS

We carried out a cross-sectional study of 102 participants with long-term type 1 diabetes and 75 controls (mean age 62 and 63 years, respectively), where 88 cases and 60 controls without diagnosed coronary artery disease completed computed tomography coronary angiography. Telomere lengths and gene expression of sirtuin 1 and growth-differentiating factor 11 were quantified in leukocytes.

RESULTS

Telomere lengths and sirtuin 1 were reduced in diabetes patients versus controls, medians (25th to 75th percentiles): 0.97 (0.82-1.15) versus 1.08 (0.85-1.29) and 0.88 (0.65-1.14) vs 1.01 (0.78-1.36), respectively, adjusted P < 0.05, both. Previous coronary artery disease in diabetes patients (n = 15) was associated with lower sirtuin 1 and growth-differentiating factor 11 messenger ribonucleic acid expression (adjusted P < 0.03, both). In the combined diabetes and control group, previous artery coronary disease (n = 18) presented with significantly shorter telomeres (adjusted P = 0.038). Newly diagnosed obstructive coronary artery disease, defined as >50% stenosis, was not associated with the investigated variables.

CONCLUSIONS

Long-term type 1 diabetes presented with reduced telomeres and sirtuin 1 expression, with additional reduction in diabetes patients with previous coronary artery disease, showing their importance for cardiovascular disease development with potential as novel biomarkers in diabetes and coronary artery disease.

摘要

目的/引言:白细胞端粒长度随年龄的缩短与冠心病有关,而与 1 型糖尿病的关系尚不清楚。我们旨在探讨与健康对照组相比,糖尿病患者的端粒长度与冠状动脉疾病的关系。相应地,研究了长寿因子 SIRT1 和生长分化因子 11。

材料和方法

我们对 102 名长期 1 型糖尿病患者和 75 名对照者(平均年龄分别为 62 岁和 63 岁)进行了横断面研究,其中 88 例和 60 例无诊断为冠心病的患者完成了计算机断层扫描冠状动脉造影。在白细胞中定量测定端粒长度和 SIRT1 和生长分化因子 11 的基因表达。

结果

与对照组相比,糖尿病患者的端粒长度和 SIRT1 降低,中位数(25 至 75 百分位数):0.97(0.82-1.15)与 1.08(0.85-1.29)和 0.88(0.65-1.14)与 1.01(0.78-1.36),调整后 P<0.05。糖尿病患者(n=15)的既往冠状动脉疾病与 SIRT1 和生长分化因子 11 信使核糖核酸表达降低相关(调整后 P<0.03,均)。在糖尿病和对照组的合并组中,既往动脉粥样硬化性冠状动脉疾病(n=18)的端粒明显缩短(调整后 P=0.038)。新诊断的阻塞性冠状动脉疾病定义为>50%狭窄,与所研究的变量无关。

结论

长期 1 型糖尿病患者的端粒和 SIRT1 表达减少,且既往有冠状动脉疾病的糖尿病患者的表达进一步减少,表明它们对心血管疾病的发展具有重要意义,可能成为糖尿病和冠状动脉疾病的新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f329/8264411/bbbff54290f3/JDI-12-1183-g002.jpg

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