ObjectiveHigh oxidative stress potentially leads to accelerated telomere shortening and consequent premature cell senescence, implicated in type 2 diabetes (T2D) development. Therefore, we studied the association of leukocyte telomere length (LTL) with the presence of T2D, as well as the effect on the patients’ LTL of plasma oxidative stress and of variation in UCP2, a gene involved in the mitochondrial production of reactive oxygen species.MethodsMean LTL was determined in 569 Caucasian, 103 South Asian and 70 Afro-Caribbean T2D patients aged from 24 to 92 years, 81 healthy Caucasian male students aged from 18 to 28 years and 367 healthy Caucasian men aged from 40 to 61 years by real-time PCR. Plasma total antioxidant status (TAOS) was measured in the T2D patients by a photometric microassay. The patients were also genotyped for the UCP2 functional variants −866G>A and A55V.ResultsAfro-Carribeans had 510 bp longer mean length compared to Caucasians (p < 0.0001) and 500 bp longer than South Asians (p = 0.004). T2D subjects displayed shorter age-adjusted LTL compared to controls [6.94(6.8–7.03) vs. 7.72(7.53–7.9), p < 0.001] with subjects in the middle and the lowest tertile of LTL having significantly higher odds ratios for T2D compared to those in the highest tertile [1.50(1.08–2.07) and 5.04(3.63–6.99), respectively, p < 0.0001]. In the patients, LTL was correlated negatively with age (r = −0.18, p < 0.0001) and positively with TAOS measures (r = 0.12, p = 0.01) after adjusting for age, while carriers of the UCP2 −866A allele had shorter age-adjusted LTL than common homozygotes [6.86(6.76–6.96) kb vs. 7.03(6.91–7.15) kb, p = 0.04].ConclusionThe present data suggest that shorter LTL is associated with the presence of T2D and this could be partially attributed to the high oxidative stress in these patients. The association of the UCP2 functional promoter variant with the LTL implies a link between mitochondrial production of reactive oxygen species and shorter telomere length in T2D.

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Background Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories (“young”: 18–60 y; “middle”: 61–75 y; and “old”: >75 y), sex, and ethnicity. Results Each unit increase in BMI corresponded to a −3.99 bp (95% CI: −5.17, −2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a −7.67 bp (95% CI: −10.03, −5.31 bp) difference. Each unit increase in BMI corresponded to a −1.58 × 10−3 unit T/S ratio (0.16% decrease; 95% CI: −2.14 × 10−3, −1.01 × 10−3) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a −2.58 × 10−3 unit T/S ratio (0.26% decrease; 95% CI: −3.92 × 10−3, −1.25 × 10−3). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.

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