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

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

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.

Highlights

Telomeres are complexes consisting of G-rich DNA sequences and specialized proteins that cap and protect the ends of chromosomes [1]
The predictive value of leukocyte telomere length (LTL) - tested by Cox regression analysis including age, gender, presence of diabetes complications, type 2 DM (T2DM) duration and LTL as continuous variables (Table 2) - disclosed that a shorter LTL predicted all-cause mortality in the three models
The present data, found in a large sample of Caucasian patients with T2DM followed for a median of 10.2 years, highlighted a complex relationship among LTL, diabetes duration, and mortality

Summary

Introduction

Telomeres are complexes consisting of G-rich DNA sequences and specialized proteins that cap and protect the ends of chromosomes [1]. Telomeric DNA is subject to attrition during mitosis, and replication can go on until a critical threshold of telomere length is reached. Telomeric DNA is highly prone to oxidative damage, and increases in oxidative stress induce its shortening [2]. For these reasons, telomere shortening is a widely used indicator of replicative senescence and cumulative genomic damage in somatic cells [3, 4], and telomere length, especially leukocyte telomere length (LTL), has extensively been investigated as a biomarker of organismal aging [5,6,7,8]. LTL determination in patients with diabetes mellitus (DM) has highlighted a significant association with the presence www.impactjournals.com/oncotarget

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