Harkin Carla, Cobice Diego, Watt Joanne, Kurth Mary Jo, Brockbank Simon, Bolton Stephanie, Johnston Frances, Strzelecka Anna, Lamont John V, Moore Tara, Fitzgerald Peter, Ruddock Mark W
Biomedical Sciences Research Institute, Ulster University, Coleraine, United Kingdom.
Clinical Studies Group, Randox Laboratories Ltd., Randox Science Park, Antrim, United Kingdom.
Front Nutr. 2023 Jan 16;9:997015. doi: 10.3389/fnut.2022.997015. eCollection 2022.
Diabetes is a major public health issue that is approaching epidemic proportions globally. Diabetes mortality is increasing in all ethnic groups, irrespective of socio-economic class. Obesity is often seen as the main contributor to an increasing prevalence of diabetes. Oxidative stress has been shown to trigger obesity by stimulating the deposition of white adipose tissue. In this study, we measured reactive aldehydes by liquid chromatography-mass spectrometry (LC-MS), in the urine and plasma of type-2 diabetic mellitus (T2DM) patients, as potential surrogates of oxidative stress. Our hypothesis was that reactive aldehydes play a significant role in the pathophysiology of diabetes, and these reactive species, may present potential drug targets for patient treatment.
Study participants [ = 86; control = 26; T2DM = 32, and diabetic nephropathy (DN) = 28] were recruited between 2019 and 2020. Urine and blood samples were collected from all participants, including a detailed clinical history, to include patient behaviours, medications, and co-morbidities. Reactive aldehyde concentrations in urine and plasma were measured using pre-column derivatisation and LC-MS, for control, T2DM and DN patients.
Reactive aldehydes were measured in the urine and plasma of control subjects and patients with T2DM and DN. In all cases, the reactive aldehydes under investigation; 4-HNE, 4-ONE, 4-HHE, pentanal, methylglyoxal, and glyoxal, were significantly elevated in the urine and serum of the patients with T2DM and DN, compared to controls ( < 0.001) (Kruskal-Wallis). Urine and serum reactive aldehydes were significantly correlated (≥0.7) ( < 0.001) (Spearman rho). The concentrations of the reactive aldehydes were significantly higher in plasma samples, when compared to urine, suggesting that plasma is the optimal matrix for screening T2DM and DN patients for oxidative stress.
Reactive aldehydes are elevated in the urine and plasma of T2DM and DN patients. Reactive aldehydes have been implicated in the pathobiology of T2DM. Therefore, if reactive aldehydes are surrogates of oxidative stress, these reactive aldehyde species could be therapeutic targets for potential drug development.
糖尿病是一个重大的公共卫生问题，在全球正呈流行趋势。糖尿病死亡率在所有种族群体中都在上升，与社会经济阶层无关。肥胖常被视为糖尿病患病率上升的主要原因。氧化应激已被证明可通过刺激白色脂肪组织沉积引发肥胖。在本研究中，我们通过液相色谱 - 质谱联用（LC - MS）测定了2型糖尿病（T2DM）患者尿液和血浆中的反应性醛类，作为氧化应激的潜在替代指标。我们的假设是，反应性醛类在糖尿病的病理生理学中起重要作用，并且这些反应性物质可能为患者治疗提供潜在的药物靶点。
2019年至2020年招募了研究参与者[共86例；对照组26例；T2DM组32例，糖尿病肾病（DN）组28例]。收集了所有参与者的尿液和血液样本，包括详细的临床病史，涵盖患者行为、用药情况和合并症。使用柱前衍生化和LC - MS测定对照组、T2DM组和DN组患者尿液和血浆中的反应性醛类浓度。
在对照组、T2DM患者和DN患者的尿液和血浆中均检测到反应性醛类。在所有情况下，所研究的反应性醛类；4 - 羟基壬烯醛（4 - HNE）、4 - 氧代壬烯醛（4 - ONE）、4 - 羟基己烯醛（4 - HHE）、戊醛、甲基乙二醛和乙二醛，与对照组相比，T2DM患者和DN患者尿液和血清中的含量显著升高（P < 0.001）（Kruskal - Wallis检验）。尿液和血清中的反应性醛类显著相关（≥0.7）（P < 0.001）（Spearman秩相关）。与尿液相比，血浆样本中反应性醛类的浓度显著更高，这表明血浆是筛查T2DM和DN患者氧化应激的最佳基质。
T2DM和DN患者尿液和血浆中的反应性醛类升高。反应性醛类与T2DM的病理生物学有关。因此，如果反应性醛类是氧化应激的替代指标，那么这些反应性醛类物质可能成为潜在药物开发的治疗靶点。
