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2型糖尿病患者的白细胞端粒长度与死亡风险

Leukocyte telomere length and mortality risk in patients with type 2 diabetes.

作者信息

Bonfigli Anna Rita, Spazzafumo Liana, Prattichizzo Francesco, Bonafè Massimiliano, Mensà Emanuela, Micolucci Luigina, Giuliani Angelica, Fabbietti Paolo, Testa Roberto, Boemi Massimo, Lattanzio Fabrizia, Olivieri Fabiola

机构信息

Scientific Direction, INRCA-IRCCS National Institute, Ancona, Italy.

Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy.

出版信息

Oncotarget. 2016 Aug 9;7(32):50835-50844. doi: 10.18632/oncotarget.10615.

Abstract

Leukocyte telomere length (LTL) shortening is found in a number of age-related diseases, including type 2 diabetes (T2DM). In this study its possible association with mortality was analyzed in a sample of 568 T2DM patients (mean age 65.9 ± 9 years), who were followed for a median of 10.2 years (interquartile range 2.2). A number of demographic, laboratory and clinical parameters determined at baseline were evaluated as mortality risk factors. LTL was measured by quantitative real-time PCR and reported as T/S (telomere-to-single copy gene ratio). Age, gender, creatinine, diabetes duration at baseline, and LTL were significantly different between T2DM patients who were dead and alive at follow-up. In the Cox regression analysis adjusted for the confounding variables, shorter LTL, older age, and longer disease duration significantly increased the risk of all-cause mortality (HR = 3.45, 95%CI 1.02-12.5, p = 0.004). Kaplan-Maier analysis also found a different cumulative mortality risk for patients having an LTL shorter than the median (T/S ≤0.04) and disease duration longer than the median (>10 years) (log-rank = 11.02, p = 0.011). Time-dependent mortality risk stratification showed that T2DM duration and LTL combined was a fairly good predictor of mortality over the first 76 months of follow-up.In conclusion, LTL combined with clinical parameters can provide additive prognostic information on mortality risk in T2DM patients.

摘要

白细胞端粒长度(LTL)缩短在包括2型糖尿病(T2DM)在内的多种与年龄相关的疾病中都有发现。在本研究中,对568例T2DM患者(平均年龄65.9±9岁)的样本进行了分析,以探讨其与死亡率之间可能存在的关联,这些患者的随访时间中位数为10.2年(四分位间距为2.2年)。对基线时测定的一些人口统计学、实验室和临床参数作为死亡风险因素进行了评估。通过定量实时PCR测量LTL,并以T/S(端粒与单拷贝基因比率)表示。随访时死亡和存活的T2DM患者在年龄、性别、肌酐、基线糖尿病病程和LTL方面存在显著差异。在对混杂变量进行校正的Cox回归分析中,较短的LTL、较高的年龄和较长的病程显著增加了全因死亡风险(HR=3.45,95%CI 1.02-12.5,p=0.004)。Kaplan-Meier分析还发现,LTL短于中位数(T/S≤0.04)且病程长于中位数(>10年)的患者累积死亡风险不同(对数秩检验=11.02,p=0.011)。时间依赖性死亡风险分层显示,在随访的前76个月中,T2DM病程和LTL相结合是死亡率的一个相当好的预测指标。总之,LTL与临床参数相结合可以为T2DM患者的死亡风险提供额外的预后信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa1/5239440/85821393a581/oncotarget-07-50835-g001.jpg

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