OBJECTIVE Oxidative stress is believed to play an important role in the pathophysiology of type 2 diabetes, but the few cohort studies that have assessed the association of oxidative stress biomarkers with type 2 diabetes incidence were small and reported inconclusive results. RESEARCH DESIGN AND METHODS We examined the associations of urinary oxidized guanine/guanosine (OxGua) levels (a biomarker of DNA/RNA oxidation) and urinary 8-isoprostane levels (a biomarker of lipid peroxidation) with type 2 diabetes incidence in 7,828 individuals initially without diabetes from a population-based German cohort study with 14 years of follow-up. Hazard ratios (HRs) (95% CIs) per 1 SD were obtained using multivariable-adjusted Cox proportional hazards regression models. RESULTS In the total population, weak but statistically significant associations with type 2 diabetes incidence were observed for OxGua levels (HR [95% CI] per 1 SD 1.05 [1.01; 1.09]) and 8-isoprostane levels (1.04 [1.00; 1.09]). Stratified analyses showed that associations of both biomarkers with type 2 diabetes incidence were absent in the youngest age-group (50-59 years) and strongest in the oldest age-group (65-75 years) of the cohort, with HR of OxGua levels 1.14 (1.05; 1.23) per 1 SD and of 8-isoprostane levels 1.22 (1.02; 1.45) per 1 SD. CONCLUSIONS These results from a large cohort study support suggestions that an imbalanced redox system contributes to the development of type 2 diabetes but suggest that this association becomes clinically apparent at older ages only, possibly as a result of reduced cellular repair capacity.

中文翻译：

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氧化损伤的DNA / RNA和8-异前列腺素水平与年龄较大的2型糖尿病的发生有关：一项大型队列研究的结果。

目的氧化应激被认为在2型糖尿病的病理生理中起着重要的作用，但是少数评估氧化应激生物标志物与2型糖尿病发生率相关性的队列研究很小，并且报告的结果尚无定论。研究设计与方法我们研究了最初在没有患病的7828例患者中，尿氧化的鸟嘌呤/鸟嘌呤（OxGua）水平（DNA / RNA氧化的生物标志物）和尿中8-异前列腺素水平（脂质过氧化的生物标志物）与2型糖尿病发生率的相关性。一项基于人群的德国队列研究对糖尿病进行了14年的随访。使用多变量调整的Cox比例风险回归模型获得每1个SD的危险比（HRs）（95％CI）。结果在总人口中，OxGua水平（每1 SD 1.05 [1.01; 1.09]的HR [95％CI]）和8-异前列腺素水平（1.04 [1.00; 1.09]）观察到与2型糖尿病发病率的关联较弱，但具有统计学意义。分层分析显示，在该队列的最年轻年龄组（50-59岁）中，这两种生物标志物与2型糖尿病的发病率均不相关，而在最老年龄组（65-75岁）中，这两种生物标志物的相关性最强，HRGua水平为每1 SD 1.14（1.05; 1.23），以及8个异前列腺素水平每1 SD 1.22（1.02; 1.45）。结论一项大型队列研究的这些结果表明，氧化还原系统失衡会导致2型糖尿病的发展，但提示这种关联仅在年纪较大时才在临床上变得明显，这可能是由于细胞修复能力降低所致。