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      Adiposity and insulin resistance correlate with telomere length in middle-aged Arabs: the influence of circulating adiponectin

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          Abstract

          Objective

          Studies in obesity have implicated adipocytokines in the development of insulin resistance, which in turn may lead to accelerated aging. In this study, we determined associations of chromosomal telomere length (TL) to markers of obesity and insulin resistance in middle-aged adult male and female Arabs with and without diabetes mellitus type 2 (DMT2).

          Design and methods

          One hundred and ninety-three non-diabetic and DMT2 subjects without complications (97 males and 96 females) participated in this cross-sectional study. Clinical data, as well as fasting blood samples, were collected. Serum glucose and lipid profile were determined using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumor necrosis factor-α, and PAI-1 were quantified using customized multiplex assay kits. High sensitive C-reactive protein (hsCRP) and angiotensin II (ANG II) were measured using ELISAs. Circulating leukocyte TL was examined by quantitative real-time PCR.

          Results

          Circulating chromosomal leukocyte TL had significant inverse associations with body mass index (BMI), systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein (LDL)- and total cholesterol, ANG II and hsCRP levels. Adiponectin, BMI, systolic blood pressure, and LDL cholesterol predicted 47% of the variance in TL ( P<0.0001). HOMA-IR was the most significant predictor for TL in males, explaining 35% of the variance ( P=0.01). In females, adiponectin accounted for 28% of the variance in TL ( P=0.01).

          Conclusion

          Obesity and insulin resistance are associated with chromosomal TL among adult Arabs. Evidence of causal relations needs further investigation. The positive association of adiponectin to TL has clinical implications as to the possible protective effects of this hormone from accelerated aging.

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          Most cited references27

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          Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study.

          S Demissie, D Levy, E J Benjamin … (2006)
          Insulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40-89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age (r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r =-0.16, P = 0.007) and urinary 8-epi-PGF(2alpha) (r = -0.16, P = 0.005) - an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 +/- 0.042 kb, normotensives = 6.07 +/- 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance.
          Article 0 comments Cited 162 times – based on 0 reviews     Review now
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            Obesity in Saudi Arabia.

            Jafri M. Abdullah, Z Khalil, A Abu Khadra … (2005)
            Obesity and overweight are well known risk factors for coronary artery disease (CAD), and are expected to be increasing in the Kingdom of Saudi Arabia (KSA) particularly among females. Therefore, we designed this study with the objective to determine the prevalence of obesity and overweight among Saudis of both gender, between the ages of 30-70 years in rural as well as in urban communities. This work is part of a major national project called Coronary Artery Disease in Saudis Study (CADISS) that is designed to look at CAD and its risk factors in Saudi population. This study is a community-based national epidemiological health survey, conducted by examining Saudi subjects in the age group of 30-70 years of selected households over a 5-year period between 1995 and 2000 in KSA. Data were obtained from body mass index (BMI) and were analyzed to classify individuals with overweight (BMI = 25-29.9 kg/m2), obesity (BMI >/=30 kg/m2) and severe (gross) obesity (BMI >/=40 kg/m2) to provide the prevalence of overweight and obesity in KSA. Data were obtained by examining 17,232 Saudi subjects from selected households who participated in the study. The prevalence of overweight was 36.9%. Overweight is significantly more prevalent in males (42.4%) compared to 31.8% of females (p<0.0001). The age-adjusted prevalence of obesity was 35.5% in KSA with an overall prevalence of 35.6% [95% CI: 34.9-36.3], while severe (gross) obesity was 3.2%. Females are significantly more obese with a prevalence of 44% than males 26.4% (p<0.0001). Obesity and overweight are increasing in KSA with an overall obesity prevalence of 35.5%. Reduction in overweight and obesity are of considerable importance to public health. Therefore, we recommend a national obesity prevention program at community level to be implemented sooner to promote leaner and consequently healthier community.
            Article 0 comments Cited 119 times – based on 0 reviews     Review now
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              The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes.

              G A Chrousos (2000)
              The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
              Article 0 comments Cited 112 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Eur J Endocrinol
                Journal ID (publisher-id): EJE
                Title: European Journal of Endocrinology
                Publisher: BioScientifica (Bristol )
                ISSN (Print): 0804-4643
                ISSN (Electronic): 1479-683X
                Publication date (Print): October 2010
                Volume: 163
                Issue: 4
                Pages: 601-607
                Affiliations
                [1 ]simpleDepartment of Biochemistry simpleCollege of Science, King Saud University PO Box 2455, Riyadh, 11451Kingdom of Saudi Arabia
                [2 ]simpleCollege of Medicine, Obesity Research Center simpleKing Saud University RiyadhKingdom of Saudi Arabia
                [3 ]simpleDiabetes and Metabolism Unit simpleWarwick Medical School, Clinical Sciences Research Institute, University of Warwick Coventry, CV4 7ALUK
                [4 ]simpleDivision of Endocrinology, Metabolism and Diabetes simpleUniversity of Athens Medical School, Children's Hospital Aghia Sophia Athens, 115 27Greece
                Author notes
                (Correspondence should be addressed to N M Al-Daghri; Email: aldaghri2000@ 123456hotmail.com )
                Article
                Publisher ID: EJE100241
                DOI: 10.1530/EJE-10-0241
                PMC ID: 2938925
                PubMed ID: 20679357
                SO-VID: db19b0f2-a6a4-4500-aab7-b881aff6342e
                Copyright © © 2010 European Society of Endocrinology
                License:

                This is an Open Access article distributed under the terms of the European Journal of Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 1 July 2010
                Date accepted : 2 August 2010
                Funding
                Funded by: King Abdul-Aziz City for Science and Technology
                Award ID: APR-26-046
                Categories
                Subject: Clinical Study

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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