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氧化引起的 DNA/RNA 损伤标志物可预测 2 型糖尿病患者基于登记的精神疾病诊断。

Markers of DNA/RNA damage from oxidation as predictors of a registry-based diagnosis of psychiatric illness in type 2 diabetic patients.

机构信息

Psychiatric Center Copenhagen (Rigshospitalet), Mental Health Services of the Capital Region, Copenhagen, Denmark.

The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Denmark.

出版信息

Psychiatry Res. 2018 Jan;259:370-376. doi: 10.1016/j.psychres.2017.11.017. Epub 2017 Nov 6.

Abstract

Oxidative stress is a potential biological mediator of the higher rates of psychiatric illness (PI) observed after the onset of type 2 diabetes (T2DM). We investigated validated urinary markers of systemic DNA/RNA damage from oxidation (8-oxodG/8-oxoGuo respectively) as predictors of incident PI in a cohort of 1381 newly diagnosed T2DM patients, who were followed prospectively for a total of 19 years after diagnosis. Psychiatric diagnoses were from Danish national registries. Patients were examined at the time of diagnosis and at a 6-year follow-up. At baseline, 8-oxodG was slightly lower in PI vs. non-PI patients, while at 6-year follow-up, 8-oxoGuo was significantly higher in PI patients. Using Cox proportional hazard models, we found that higher levels of 8-oxodG at 6-year follow-up significantly predicted lower incidence of PI after the adjustment for confounders. In a subgroup analysis, this association was most predominant in minor PIs (unipolar depression and anxiety) compared to major PIs such as schizophrenia and bipolar disorder. These observations indicate that higher levels of systemic oxidative stress are not associated with a higher risk of PI after T2DM onset. Only PI patients treated in hospital care were included in the registries, and the conclusion thus only applies to these individuals.

摘要

氧化应激是 2 型糖尿病(T2DM)发病后精神疾病(PI)发病率较高的潜在生物学介质。我们研究了经过验证的尿液生物标志物,用于衡量全身 DNA/RNA 氧化损伤(分别为 8-oxodG/8-oxoGuo),以预测 1381 例新诊断的 T2DM 患者中 PI 的发病情况,这些患者在诊断后总共进行了 19 年的前瞻性随访。精神疾病诊断来自丹麦国家登记处。患者在诊断时和 6 年后进行检查。在基线时,PI 患者的 8-oxodG 略低于非 PI 患者,而在 6 年后随访时,PI 患者的 8-oxoGuo 明显升高。使用 Cox 比例风险模型,我们发现,在调整混杂因素后,6 年后随访时较高的 8-oxodG 水平显著预测 PI 的发病率降低。在亚组分析中,与精神分裂症和双相情感障碍等主要 PI 相比,这种关联在较轻的 PI(单相抑郁和焦虑)中更为明显。这些观察结果表明,在 T2DM 发病后,较高的系统性氧化应激水平与 PI 风险增加无关。只有在医院接受治疗的 PI 患者才被纳入登记处,因此该结论仅适用于这些个体。

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