Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.

Short leukocyte telomere length (LTL) has been associated with atherosclerosis in cross-sectional studies, but the prospective relationship between telomere shortening and risk of developing carotid atherosclerosis has not been well-established. This study examines whether LTL at baseline predicts incidence and progression of carotid atherosclerosis in American Indians in the Strong Heart Study. The analysis included 2,819 participants who were free of overt cardiovascular disease at baseline (2001-2003) and were followed through the end of 2006-2009 (average 5.5-yr follow-up). Discrete atherosclerotic plaque was defined as focal protrusion with an arterial wall thickness ≥50% the surrounding wall. Carotid progression was defined as having a higher plaque score at the end of study follow-up compared to baseline. Associations of LTL with incidence and progression of carotid plaque were examined using Cox proportional hazard regression, adjusting for standard coronary risk factors. Compared to participants in the highest LTL tertile, those in the lowest tertile had significantly elevated risk for both incident plaque (HR, 1.49; 95% CI, 1.09–2.03) and plaque progression (HR, 1.61; 95% CI, 1.26–2.07). Our results provide initial evidence for a potential prognostic utility of LTL in risk prediction for atherosclerosis.

Background: Obesity is an independent risk factor for diabetes and cardiovascular disease. Telomere length shortens progressively with age, and shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders. However, the association between LTL and obesity has not been well established. Objective: To examine the association of LTL with obesity and related traits in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003), independent of known risk factors. Methods: A total of 3,162 participants (18-93 years old, 1,938 women) from 94 multigenerational families were included in this analysis. Obesity-related traits included body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. LTL was measured by quantitative PCR. Association of LTL (continuous or in quintiles) with each adiposity index was examined using generalized linear mixed model, adjusting for age, sex, study center, education, lifestyle factors (current smoking, current drinking, physical activity, and total energy intake), hypertension (yes/no) and diabetes (yes/no). The association of LTL with prevalent obesity (BMI ≥30 kg/m2) was examined by multivariate logistic regression using the GLIMMIX procedure in SAS 9.3. Results: Prevalence of obesity was 59.6% (1,883 of 3,162). LTL was negatively correlated with age (r=-0.3, P<0.0001). Obese participants had significantly shorter LTL than non-obese participants (age-adjusted P=0.0004). Multivariate regression analyses demonstrated that, LTL was significantly and inversely associated with all obesity indices (β= -2.68 [95% confidence interval (CI), -3.96 [[Unable to Display Character: &#8210;]] -1.40] for BMI; -6.28 [95% CI, -9.29 [[Unable to Display Character: &#8210;]] -3.27] for waist circumference; -3.95 [95% CI, -6.61 [[Unable to Display Character: &#8210;]] -1.29] for hip circumference; and -0.02 [95% CI, -0.03 [[Unable to Display Character: &#8210;]] -0.01] for waist-to-hip ratio). Participants with shorter LTL had significantly larger BMI (P trend across quintiles =0.0006), waist circumference (P trend =0.0005), hip circumference (P trend =0.01), and waist-to-hip ratio (P trend =0.002) compared to those with longer LTL. Multivariate-adjusted odds ratio (95% CI) for prevalent obesity was 1.32 (1.05-1.67), 1.29 (0.99-1.67), 1.29 (1.01-1.65) and 1.18 (0.89-1.57), respectively, for the 1st through 4th quintiles of LTL in comparison with the 5th quintile (P for trend =0.02). Excluding participants with diabetes and cardiovascular disease did not change our results. Conclusion: Shorter LTL was significantly associated with obesity and related measures in American Indians, independent of known risk factors. Our results may shed light on the complex pathophysiology of obesity and its related disorders.