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Insulin resistance is associated with cardiac aging and shorter leukocyte telomere length

Session Poster session 2

Speaker Ekaterina Plokhova

Event : ESC Congress 2014

  • Topic : basic science
  • Sub-topic : Basic Science - Cardiac Biology and Physiology
  • Session type : Poster Session

Authors : EV Plokhova (Moscow,RU), DU Akasheva (Moscow,RU), ON Tkacheva (Moscow,RU), ID Strazhesko (Moscow,RU), AS Kruglikova (Moscow,RU), VS Pikhtina (Moscow,RU), EN Dudinskaya (Moscow,RU), IN Ozerova (Moscow,RU), NV Brailova (Moscow,RU), SA Boytsov (Moscow,RU)

E.V. Plokhova1 , D.U. Akasheva1 , O.N. Tkacheva1 , I.D. Strazhesko1 , A.S. Kruglikova1 , V.S. Pikhtina1 , E.N. Dudinskaya1 , I.N. Ozerova1 , N.V. Brailova1 , S.A. Boytsov1 , 1National Center of Preventive Medicine - Moscow - Russian Federation ,

European Heart Journal ( 2014 ) 35 ( Abstract Supplement ), 277

Purpose: Cardiac aging is an independent risk factor for cardiovascular disease. The main signs of the aged heart are a thickening of the left (LV) ventricular walls and LV diastolic dysfunction. Insulin resistance (IR) is exacerbating aging-related changes in the cardiac structure and function. One possible mechanism underlying IR-induced cardiac dysfunction with advancing age could be related to decreased telomeres length of leukocytes (LTL). Telomeres are tandem repeats of the DNA sequence at the end of chromosomes and protect DNA molecule from damage. LTL is a marker of replicative aging. Our hypothesis is that IR led to shorter telomeres and senescent phenotypes in the heart.

Methods: We investigated 118 non-obese participants aged 60 to 85 years without history of CVD, diabetes and regular drug medication. All the volunteers underwent standardized transthoracic echocardiography with the available system (iE33; Philips), had an oral glucose tolerance test. HOMA-IR was calculated as fasting insulin (mU/ml) x fasting glucose (mmol/l) (mmol/l)/22.5. IR was diagnosed in case of HOMA-IR elevation >2.5 based on reference. LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).

Results: In older individuals HOMA-IR was significantly positively related to LV septal wall thickness (r=0.489, p<0.001), LV posterior wall thickness (r=0.458, p<0.001), E/Em (r=0.379, p<0.01) and inversely correlated with E/A (r= -0,320, p<0.01), Em/Am (r= -0.342, p<0.01). LTL was significantly and independently associated with age (β= -0.026, p=0.015) and HOMA-IR (β= -0.176, p=0.027). Results of analysis of variance (ANOVA) showed that LTL was significantly related to diastolic function indices regardless of age (p<0.001). Older subjects with higher HOMA-IR had a shorter telomeres (p=0.046) and more expressed LV hypertrophy and diastolic dysfunction to compared to subjects with normal HOMA-IR. Individuals with IR did not significantly differ from those with normal HOMA-IR in the proportion of smokers, or levels of blood pressure and BMI.

Conclusions: These findings suggest that insulin resistance is associated with more expressed signs of the aging heart and shorter LTL. Accelerated telomere attrition appears to be the mechanism by which impaired insulin resistance develops into cardiac aging.

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