Article

Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction.

Dept. of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, Ancona, Italy.
Atherosclerosis (Impact Factor: 3.71). 05/2009; 206(2):588-93. DOI: 10.1016/j.atherosclerosis.2009.03.034
Source: PubMed

ABSTRACT We performed a cross-sectional study to examine the differences in leukocyte telomere length among three groups of subjects: patients with type 2 diabetes mellitus without history of previous myocardial infarction (Type2DM), patients with type 2 diabetes mellitus with evidence of previous myocardial infarction (Type2DM+MI), and healthy control subjects (CTR). The main objective of the present study is to investigate differences in telomere length between the studied groups of subjects, with the aim to clarify if telomere length could be a reliable marker associated with MI in Type2DM patients. Secondary end point is the identification of associations between leukocyte telomere length and selected variables related to glycemic control, pro-inflammatory status and lipidic profile.
A total of 272 elderly subjects, 103 Type2DM (mean age 70+/-4 years, 59% males), 65 Type2DM+MI (mean age 68+/-7 years, 68% males), and 104 CTR (mean age 69+/-7 years, 50% males) were studied. Telomere length, defined as T/S (Telomere-Single copy gene ratio), was determined in leukocytes by quantitative real-time polymerase chain reaction (real-time PCR)-based assay. Moreover, we assessed: (1) high sensitive C reactive protein (hsCRP), fibrinogen and plasminogen-activator inibitor-1 (PAI-1) as inflammatory markers; (2) fasting glucose, insulin, glycated haemoglobin (HbA1C) and waist-to-hip ratio as markers of glycemic control; (3) total-cholesterol, HDL-cholesterol and triglycerides as markers of lipidic profile, in all sample population. The use of statins and sulfonylurea, as well as the presence of some relevant diabetes complications (nephropathy and retinopathy) were also assessed.
Type2DM+MI elderly patients have leukocyte telomere lengths shorter than those of Type2DM (without MI) and healthy CTR. Moreover, glucose, HbA1C and waist-to-hip ratio, variables related to glycemic control, showed a significant inverse correlation with leukocyte telomeres length.

1 Bookmark
 · 
135 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Several epidemiological studies have examined the association between shortened telomere length and type 2 diabetes mellitus (T2DM), while the results remained conflicting. We conducted a meta-analysis to derive a more precise estimation of the relationship between them. We systematically reviewed the databases of PubMed, EMBASE, and Web of Science for all studies on the association between telomere length and T2DM. We conducted this study assessed by STATA 11.0. Data were summarized using random-effects or fixed-effects meta-analysis. The heterogeneity and publication bias among studies were examined by using χ(2)-based Q statistic test and Egger's test, respectively. Nine cohorts consisting of 5759 cases and 6518 controls were selected into the meta-analysis. The results indicated that shortened telomere length was significantly associated with T2DM risk (OR: 1.291; 95% CI: 1.112, 1.498; P<0.001) with heterogeneity (I(2) = 71.6%). When three cohorts responsible for the heterogeneity were excluded, the pooled OR for the remaining cohorts indicated a significant association between shortened telomere length and T2DM (OR: 1.117; 95% CI: 1.002, 1.246; P = 0.045) without heterogeneity. We found a statistically significant association between shortened telomere length and T2DM.
    PLoS ONE 01/2013; 8(11):e79993. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Telomeres are the tips of chromosomes and consist of proteins and hexanucleotide tandem repeats of DNA. The DNA repeats are shortened at each mitotic division of normal cells, and the telomere length chronicles how many divisions the cell has undergone. Thus, telomere length is a marker of fundamental biological pathways. It has been possible to measure telomere length for more than 20 years, and it has been established that telomere length is associated with age, sex and lifestyle factors. Here, the current knowledge of telomere length as a biomarker of disease susceptibility and mortality will be reviewed. In addition, technical difficulties and the reasons why measurement of telomeres has still not been introduced into routine clinical practice will be discussed. Findings from recent studies conducted in many thousands of individuals indicate that telomere length is not-or at best only marginally-independently associated with risk of common disorders such as cardiovascular, pulmonary and neoplastic diseases. However, in sufficiently powered studies, short telomeres are repeatedly and independently found to be associated with increased risk of early death in the general population or in subsets of individuals. This indicates that measurement of telomeres could be a valuable prognostic biomarker in many clinical settings. However, whether short telomeres are a causal factor for or simply a marker of increased risk of early death must be determined. Finally, how Mendelian randomization studies could clarify this issue, and which clinical studies might be carried out to refine this very promising biomarker for routine clinical use will be considered.
    Journal of Internal Medicine 11/2013; 274(5):399-413. · 6.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of atherosclerosis, an age-related disorder, may be due to a premature biological ageing. Cellular senescence, the finite replicative lifespan of cells, plays a critical role in the pathogenesis of atherosclerosis. The biological mechanism that triggers the onset of cellular senescence is thought to be telomere shortening. The two major mechanisms responsible for telomere shortening are the end-replication problem, oxidative DNA damage as well as inflammation induced by environmental risk factors. Repair of the endothelium depends on the presence of endothelial progenitor cells which depends on the hematopoietic stem cells (HSC) reserves. In numerous past studies, short LTL has been associated with atherosclerosis. Here we review the literature on telomere biology and coronary artery disease (CAD).
    Nutrition, Metabolism and Cardiovascular Diseases. 01/2014;

Full-text

Download
48 Downloads
Available from
May 20, 2014