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

Abstract

// Anna Rita Bonfigli 1 , Liana Spazzafumo 2 , Francesco Prattichizzo 3 , Massimiliano Bonafè 4 , Emanuela Mensà 5 , Luigina Micolucci 6 , Angelica Giuliani 6 , Paolo Fabbietti 2 , Roberto Testa 7 , Massimo Boemi 8 , Fabrizia Lattanzio 1 and Fabiola Olivieri 5,6 1 Scientific Direction, INRCA-IRCCS National Institute, Ancona, Italy 2 Center of Biostatistics, INRCA-IRCCS National Institute, Ancona, Italy 3 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Rosselló, Barcelona, Spain 4 Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy 5 Center of Clinical Pathology and Innovative Therapy, National Institute INRCA-IRCCS, Ancona, Italy 6 Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy 7 Experimental Models in Clinical Pathology, INRCA-IRCCS National Institute, Ancona, Italy 8 Metabolic Diseases and Diabetology Unit, INRCA-IRCCS National Institute, Ancona, Italy Correspondence to: Anna Rita Bonfigli, email: // Keywords : telomere shortening, type 2 diabetes, mortality, aging, Gerotarget Received : April 19, 2016 Accepted : July 01, 2016 Published : July 15, 2016 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.