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

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.

Leukocyte Telomere Length in Relation to 17 Biomarkers of Cardiovascular Disease Risk: A Cross-Sectional Study of US Adults

“…A meta-analysis identifying an association between LTL and diabetes did not examine what potential confounding factors were controlled for [53]. In addition, studies showing greater mortality for those with shorter telomere length within diabetic populations [54] are more informative about the role of telomere length in the progression of disease rather than in the general population. With respect to kidney function, many prior studies reporting an association with LTL were in clinical samples, not in the general population [55].…”

Where Metabolism Meets Senescence: Focus on Endothelial Cells

“…The aberrant non-enzymatic glycation of circulating and intracellular proteins is a key determinant of T2DM cardiovascular complications (Mapanga and Essop, 2016). Endothelial dysfunction (ED) and senescence are "historically" considered two consequences of T2DM (Bonfigli et al, 2016;Prattichizzo et al, 2018a,d), possibly as a result of the overabundance of senescencepromoting, endothelium-damaging factors in the bloodstream of these patients, e.g., pro-oxidant molecules, glucose, and lipids (Prattichizzo et al, 2018c). In particular, the role of EC senescence has been emphasized in both the development of T2DM and of its CV complications.…”

Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial

“…We also observed in our sample that obesity/overweight (elevated BMI and WC), associated with hyperhomocysteinemia caused by C677T polymorphism, can trigger inflammation and oxidative stress by activating the NF-κB signaling pathway [65,66]. Furthermore, the production of Reactive Oxygen Species (ROS) could selectively change the pattern of interleukins' expression [67][68][69] and tumor necrosis factor-alpha (TNF-α). TNF-α is an important inflammatory marker that induces the synthesis of cytokine mediators IL-1β and IL-6 [70,71], acting synergistically and intensifying inflammation [72][73][74].…”