Short leukocyte telomere length is associated with obesity in American Indians: The strong heart family study

Chen, Shufeng; Yeh, Fawn; Lin, Jue; Matsuguchi, Tet; Blackburn, Elizabeth H.; Lee, Elisa T.; Howard, Barbara V.; Zhao, Jinying

doi:10.18632/aging.100664

Cited by 59 publications

(57 citation statements)

References 43 publications

(49 reference statements)

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“…Thus, genetic factors [16] and the intrauterine environment [17][18][19] might play a role in fashioning TL, which, in turn, may have a major impact on the risk of metabolic diseases in adulthood. A recent clinical study in American Indians showed that short LTL was associated with the incidence of type 2 diabetes mellitus [20] and obesity [21]. The authors hypothesised that LTL could be used as a predictive marker of diabetes development in American Indians.…”

Section: Introductionmentioning

confidence: 99%

A short leucocyte telomere length is associated with development of insulin resistance

et al. 2016

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Aims/hypothesis A number of studies have shown that leucocyte telomere length (LTL) is inversely associated with insulin resistance and type 2 diabetes mellitus. The aim of the present longitudinal cohort study, utilising a twin design, was to assess whether shorter LTL predicts insulin resistance or is a consequence thereof. Methods Participants were recruited between 1997 and 2000 through the population-based national Danish Twin Registry to participate in the GEMINAKAR study, a longitudinal evaluation of metabolic disorders and cardiovascular risk factors. Baseline and follow-up measurements of LTL and insulin resistance over an average of 12 years were performed in a subset of the Registry consisting of 338 (184 monozygotic and 154 dizygotic) same-sex twin pairs. Results Age at baseline examination was 37.4± 9.6 (mean ± SD) years. Baseline insulin resistance was not associated with age-dependent changes in LTL (attrition) over the follow-up period, whereas baseline LTL was associated with changes in insulin resistance during this period. The shorter the LTL at baseline, the more pronounced was the increase in insulin resistance over the follow-up period (p < 0.001); this effect was additive to that of BMI. The co-twin with the shorter baseline LTL displayed higher insulin resistance at follow-up than the co-twin with the longer LTL. Conclusions/interpretation These findings suggest that individuals with short LTL are more likely to develop insulin resistance later in life. By contrast, presence of insulin resistance does not accelerate LTL attrition.

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Section: Introductionmentioning

confidence: 99%

A short leucocyte telomere length is associated with development of insulin resistance

et al. 2016

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“…Thus far, several traditional and newly emerging risk factors are associated with CHD risk, 6,7 some of which, such as glycemic traits, lipids, and obesity, are also closely related to telomere shortening. [8][9][10][11] Thus, these may act as potential mediators that lie in the pathway from telomere shortening to increased risk of CHD.…”

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confidence: 99%

Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease

Zhan

Karlsson

et al. 2017

Circ Res

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In this study, we aim to examine metabolic risk factors as possible mediators in the causal relationship between genetically determined TL and CHD using a network MR method 12 from summarized genome-wide association study (GWAS) data. The rationale for focusing on metabolic risk factors is based on the following: (1) these metabolic risk factors explain a large proportion Molecular Medicine© 2017 American Heart Association, Inc. Rationale: Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention.Objective: To examine whether metabolic risk factors for CHD mediate the causal pathway from short TL to increased risk of CHD using a network Mendelian randomization design. Methods and Results:Summary statistics from several genome-wide association studies were used in a 2-sample Mendelian randomization study design. Network Mendelian randomization analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality-was performed to examine the causal association between telomeres and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D Consortium data were used (case=22 233 and control=64 762) for CHD, and other consortia data were used for metabolic traits (fasting insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip ratio). One-unit increase of genetically determined TL was associated with −0.07 (95% confidence interval, −0.01 to −0.12; P=0.01) lower log-transformed fasting insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of CHD. Higher genetically determined log-transformed fasting insulin level was associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01-3.41; P=0.04). Conclusions:

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“…Obesity is associated with significantly shortened leukocyte telomere length even when controlling for covariates such as age, smoking, C-reactive protein (CRP), diabetes, and hypertension [41]. Severely obese patients demonstrated shorter relative telomere length at baseline and one year after bariatric surgery, irrespective of whether they also had metabolic syndrome [42].…”

Section: Telomere Length and Dynamics In Somatic Diseasesmentioning

confidence: 99%

Telomeres, Early-Life Stress and Mental Illness

Ridout

Kao

et al. 2015

Clinical Challenges in the Biopsychosocial Interface

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Telomeres are structures of tandem TTAGGG repeats at the ends of chromosomes which preserve the encoding DNA by serving as a disposable brake to terminate DNA duplication during chromosome replication. In this process, the telomere itself shortens with each cell division, and can consequently be thought of as a cellular “clock” reflecting the age of a cell and the time until senescence. Telomere shortening, and changes in levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress [ELS]), and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying biomarker of stress response that crosses the brain/body distinction often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine in the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

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Short leukocyte telomere length is associated with obesity in American Indians: The strong heart family study

Cited by 59 publications

References 43 publications

A short leucocyte telomere length is associated with development of insulin resistance

A short leucocyte telomere length is associated with development of insulin resistance

Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease

Telomeres, Early-Life Stress and Mental Illness

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