School of Nursing, Peking University, Beijing, China.
School of Nursing, Peking University, Beijing, China.
Free Radic Biol Med. 2021 Aug 1;171:91-98. doi: 10.1016/j.freeradbiomed.2021.05.015. Epub 2021 May 12.
Chronic hyperglycemia, proinflammatory state, and oxidative stress are implicated in the etiology of mild cognitive impairment (MCI) in type 2 diabetes mellitus (T2DM) patients. However, roles and mechanisms of the diabetes-related dys-regulation of serum d-ribose in the pathogenesis remain unclear. This study was to assess: 1) changes of serum d-ribose in T2DM patients with or without MCI compared with healthy controls; and 2) associations of serum d-ribose with key biomarkers of ribosylation [advanced glycation end products (AGEs) and receptor for advanced glycation end products (RAGE)], inflammation (IL-6 and NF-κB) and oxidative stress [oxidized low density lipoproteins (ox-LDL), advanced oxidation protein products (AOPP), total thiol, and non-protein thiol)]. A cross-sectional study was conducted with 1564 initial participants including 362 T2DM patients. Based on their fasting blood glucose concentrations and Montreal cognitive assessment (MoCA) scores, we selected 89 participants and divided them into three groups: 27 healthy controls, 26 T2DM patients with normal cognition, 36 T2DM patients with MCI. All participants were gone through standard anthropometric tests and biochemical examinations of serum clinical profiles and concentrations of d-ribose, AGE, RAGE, IL-6, NF-κB, ox-LDL, AOPP, total thiol, and non-protein thiol. Serum concentrations of d-ribose, ox-LDL, and AOPP were greater (P < 0.05) in the T2DM-MCI patients than that in the T2DM or controls. Serum d-ribose exhibited a positive correlation (P < 0.05) with serum AGEs, RAGE, ox-LDL, and fasting blood glucose, but a negative correlation (P < 0.05) with MoCA score. This negative relationship remained (P < 0.05) after adjusting various covariates, and was found to be mediated (P < 0.05) by serum ox-LDL. In conclusion, our results reveal serum ox-LDL as a potential mediator for the inverse relationship between the elevation of serum d-ribose concentration and the decline of cognitive performance in the T2DM-MCI patients.
慢性高血糖、促炎状态和氧化应激与 2 型糖尿病（T2DM）患者轻度认知障碍（MCI）的发病机制有关。然而，糖尿病相关的血清 D-核糖失调在发病机制中的作用和机制尚不清楚。本研究旨在评估：1）与健康对照组相比，T2DM 患者伴或不伴 MCI 时血清 D-核糖的变化；2）血清 D-核糖与核糖基化的关键生物标志物[晚期糖基化终产物（AGEs）和晚期糖基化终产物受体（RAGE）]、炎症（IL-6 和 NF-κB）和氧化应激[氧化低密度脂蛋白（ox-LDL）、氧化型高级蛋白产物（AOPP）、总巯基和非蛋白巯基]之间的相关性。采用横断面研究方法，纳入了 1564 名初诊患者，其中包括 362 名 T2DM 患者。根据空腹血糖浓度和蒙特利尔认知评估（MoCA）评分，我们选择了 89 名参与者，并将他们分为三组：27 名健康对照者、26 名认知正常的 T2DM 患者和 36 名 MCI 的 T2DM 患者。所有参与者均进行了标准的人体测量学检查和生化检查，包括血清临床特征和 D-核糖、AGE、RAGE、IL-6、NF-κB、ox-LDL、AOPP、总巯基和非蛋白巯基的浓度。与 T2DM 患者或对照组相比，T2DM-MCI 患者的血清 D-核糖、ox-LDL 和 AOPP 浓度更高（P<0.05）。血清 D-核糖与血清 AGEs、RAGE、ox-LDL 和空腹血糖呈正相关（P<0.05），与 MoCA 评分呈负相关（P<0.05）。在调整了各种混杂因素后，这种负相关仍然存在（P<0.05），并且发现其由血清 ox-LDL 介导（P<0.05）。综上所述，我们的研究结果表明，血清 ox-LDL 可能是 T2DM-MCI 患者血清 D-核糖浓度升高与认知功能下降之间负相关的潜在介导因素。
