Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases

Abstract

BackgroundChronic inflammation and oxidative stress might be considered the key mechanisms of aging. Insulin resistance (IR) is a phenomenon related to inflammatory and oxidative stress. We tested the hypothesis that IR may be associated with cellular senescence, as measured by leukocyte telomere length (LTL), and arterial stiffness (core feature of arterial aging), as measured by carotid-femoral pulse wave velocity (c-f PWV).MethodsThe study group included 303 subjects, mean age 51.8 ±13.3 years, free of known cardiovascular diseases and regular drug consumption. For each patient, blood pressure was measured, blood samples were available for biochemical parameters, and LTL was analyzed by real time q PCR. C-f PWV was measured with the help of SphygmoCor. SAS 9.1 was used for statistical analysis.ResultsThrough multiple linear regression analysis, c-f PWV is independently and positively associated with age (p = 0.0001) and the homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.0001) and independently negatively associated with LTL (p = 0.0378). HOMA-IR seems to have a stronger influence than SBP on arterial stiffness. In all subjects, age, HOMA-IR, LTL, and SBP predicted 32% of the variance in c-f PWV. LTL was inversely associated with HOMA-IR (p = 0.0001) and age (p = 0.0001). In all subjects, HOMA-IR, age, sex, and SBP predicted 16% of the variance in LTL.ConclusionsThese data suggest that IR is associated with cell senescence and arterial aging and could, therefore, become the main target in preventing accelerated arterial aging, besides blood pressure control. Research in telomere biology may reveal new ways of estimating cardiovascular aging and risk.

Leukocyte telomere length and mortality risk in patients with type 2 diabetes

“…The significantly shorter LTL measured in T2DM patients compared with healthy subjects over a wide age range has lent support to the hypothesis, which is also consistent with the beta cell failure and the increased senescence of vascular endothelial and smooth muscle cells seen in hyperglycemic media [49]. The notion is further reinforced by the inverse age-dependent relationship documented between LTL and insulin resistance [50]. Notably, in vivo evidence of increased senescence in both atherosclerotic plaques and renal tissue of diabetes patients suggest the relevance of this phenomenon to the vascular complications of diabetes [20, 50].…”

“…The notion is further reinforced by the inverse age-dependent relationship documented between LTL and insulin resistance [50]. Notably, in vivo evidence of increased senescence in both atherosclerotic plaques and renal tissue of diabetes patients suggest the relevance of this phenomenon to the vascular complications of diabetes [20, 50]. Increased beta cell senescence in diabetic patients has also been demonstrated [51].…”

Diabetes Mellitus, ArterialWall, and Cardiovascular Risk Assessment

“…Ba-PWV was independently and positively associated with fasting plasma glucose, with one-hour post-challenge glucose or with HOMA-IR index in general population, in the pre-diabetic subjects, and in non-diabetic hypertensive subjects [ 105 , 106 , 107 , 108 , 109 ]. Finally, a recent study in middle-aged subjects free of CVD demonstrated the relationships of Cf-PWV with HOMA-IR index (direct) and telomere length (inverse), and suggested that insulin resistance linked with chronic inflammation can enhance telomere shortening (a marker of cellular senescence), and thus induce accelerated vascular aging [ 110 ].…”

Nutrition and lifestyle in healthy aging: the telomerase challenge

“…Lifestyle factors known to modulate aging and age-related diseases might also affect telomerase activity. Obesity [ 42 ], insulin resistance [ 43 , 44 ], and cardio-vascular disease processes [ 45 , 46 ], which are related to oxidative stress and inflammation, have all been linked to shorter telomeres. Smoking, exposure to pollution, lower physical activity, psychological stress, and unhealthy diet significantly increase the oxidative burden and the rate of telomere shortening [ 47 - 53 ].…”