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      Lymphocytes of Type 2 Diabetic Women Carry a High Load of Stable Chromosomal Aberrations : A Novel Risk Factor for Disease-Related Early Death

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          Abstract

          OBJECTIVE—Diabetes is associated with an increased risk of death in women. Oxidative stress due to chronic hyperglycemia leads to the generation of reactive oxygen species and loss of chromosomal integrity. To clarify whether diabetes is a premature aging syndrome, we determined telomere erosion dynamics and occurrence of structural chromosomal aberrations in women of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

          RESEARCH DESIGN AND METHODS—Telomere lengths and karyotypes were examined in peripheral blood mononuclear cells. Regarding these parameters, surviving and deceased type 2 diabetic women of the LURIC study were compared with nondiabetic LURIC women with or without coronary heart disease and with healthy female control subjects.

          RESULTS—Significantly enhanced telomere attrition was seen in all LURIC subjects compared with healthy control subjects. Although the average telomere-length loss is equivalent to well >10 years of healthy aging, telomere erosion was not associated with outcome within the LURIC cohort. However, strikingly high numbers of stable chromosomal aberrations were found in type 2 diabetic women but not in LURIC disease control subjects or in healthy individuals. Furthermore, within the younger age- groups, deceased type 2 diabetes patients had significantly more marker chromosomes than the surviving type 2 diabetic patients.

          CONCLUSIONS—All women at high risk for cardiovascular death have accelerated telomere erosion, not caused by type 2 diabetes per se but likely linked to other risk factors, including dyslipidemia. By contrast, the occurrence of marker chromosomes is associated with type 2 diabetes and is a novel risk factor for type 2 diabetes–related early death.

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          Most cited references53

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          Obesity, cigarette smoking, and telomere length in women.

          Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
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            Major causes of death among men and women in China.

            With China's rapid economic development, the disease burden may have changed in the country. We studied the major causes of death and modifiable risk factors in a nationally representative cohort of 169,871 men and women 40 years of age and older in China. Baseline data on the participants' demographic characteristics, medical history, lifestyle-related risk factors, blood pressure, and body weight were obtained in 1991 with the use of a standard protocol. The follow-up evaluation was conducted in 1999 and 2000, with a follow-up rate of 93.4 percent. We documented 20,033 deaths in 1,239,191 person-years of follow-up. The mortality from all causes was 1480.1 per 100,000 person-years among men and 1190.2 per 100,000 person-years among women. The five leading causes of death were malignant neoplasms (mortality, 374.1 per 100,000 person-years), diseases of the heart (319.1), cerebrovascular disease (310.5), accidents (54.0), and infectious diseases (50.5) among men and diseases of the heart (268.5), cerebrovascular disease (242.3), malignant neoplasms (214.1), pneumonia and influenza (45.9), and infectious diseases (35.3) among women. The multivariate-adjusted relative risk of death and the population attributable risk for preventable risk factors were as follows: hypertension, 1.48 (95 percent confidence interval, 1.44 to 1.53) and 11.7 percent, respectively; cigarette smoking, 1.23 (95 percent confidence interval, 1.18 to 1.27) and 7.9 percent; physical inactivity, 1.20 (95 percent confidence interval, 1.16 to 1.24) and 6.8 percent; and underweight (body-mass index [the weight in kilograms divided by the square of the height in meters] below 18.5), 1.47 (95 percent confidence interval, 1.42 to 1.53) and 5.2 percent. Vascular disease and cancer have become the leading causes of death among Chinese adults. Our findings suggest that control of hypertension, smoking cessation, increased physical activity, and improved nutrition should be important strategies for reducing the burden of premature death among adults in China. Copyright 2005 Massachusetts Medical Society.
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              Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study.

              Inter-individual differences in biological ageing could affect susceptibility to coronary heart disease. Our aim was to determine whether mean leucocyte telomere length is a predictor of the development of coronary heart disease. We compared telomere lengths at recruitment in 484 individuals in the West of Scotland Primary Prevention Study (WOSCOPS) who went on to develop coronary heart disease events with those from 1058 matched controls who remained event free. We also investigated whether there was any association between telomere length and observed clinical benefit of statin treatment in WOSCOPS. Mean telomere length decreased with age by 9% per decade (95% CI 3.6-14.1; p=0.001) in controls; much the same trend was seen in cases (-5.9% per decade, -3.1 to 14.1; p=0.1902). Individuals in the middle and the lowest tertiles of telomere length were more at risk of developing a coronary heart disease event than were individuals in the highest tertile (odds ratio [OR] for coronary heart disease: 1.51, 95% CI 1.15-1.98; p=0.0029 in the middle tertile; 1.44, 1.10-1.90, p=0.0090 in the lowest). In placebo-treated patients, the risk of coronary heart disease was almost double in those in the lower two tertiles of telomere length compared with those in the highest tertile (1.93, 1.33-2.80, p=0.0005 in the middle tertile; 1.94, 1.33-2.84, p=0.0006 in the lowest). By contrast, in patients treated with pravastatin, the increased risk with shorter telomeres was substantially attenuated (1.12, 0.75-1.69, p=0.5755 in the middle tertile; 1.02, 0.68-1.52, p=0.9380 in the lowest). Mean leucocyte telomere length is a predictor of future coronary heart disease events in middle-aged, high-risk men and could identify individuals who would benefit most from statin treatment. Our findings lend support to the hypothesis that differences in biological ageing might contribute to the risk--and variability in age of onset--of coronary heart disease.
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                Author and article information

                Journal
                Diabetes
                diabetes
                Diabetes
                American Diabetes Association
                0012-1797
                1939-327X
                November 2008
                : 57
                : 11
                : 2950-2957
                Affiliations
                [1 ]Division of Endocrinology and Diabetes, Graduate School Molecular Endocrinology and Diabetes, Ulm University, Ulm, Germany
                [2 ]Institute of Pathology, Ulm University, Ulm, Germany
                [3 ]Institute of Human Genetics, Ulm University, Ulm, Germany
                [4 ]Cardiology Group, Frankfurt-Sachsenhausen, Germany
                [5 ]Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
                [6 ]Ludwigshafen Risk and Cardiovascular Health Study, Freiburg, Germany
                Author notes

                Corresponding author: Silke Brüderlein, silke.bruederlein@ 123456uniklinik-ulm.de

                Article
                57112950
                10.2337/db08-0274
                2570391
                18650367
                8d6e049b-1745-4116-b5d5-5128c4118081
                Copyright © 2008, American Diabetes Association

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 25 February 2008
                : 17 July 2008
                Categories
                Metabolism

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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