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.

Inflammation causes widespread endothelial dysfunction, reduces vascular NO bioavailability and increases oxidative stress. These actions are partially reversible with local anti-oxidants. These findings suggest a role for reactive oxygen species in inflammation-induced endothelial dysfunction.

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A common CRP gene polymorphism is associated with important differences in CRP concentrations, free from confounding. The null association of this variant with coronary events suggests possible residual confounding (or reverse causation) in the CRP-coronary event association in observational studies, though the confidence limits are still compatible with a modest causal effect. Additional studies of genotype (or haplotype) and coronary events would help clarify whether or not the link between CRP and coronary events in observational studies is causal.