Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates.
Health Engineering Innovation Center, Khalifa University, Abu Dhabi, United Arab Emirates.
J Diabetes Investig. 2021 Oct;12(10):1881-1889. doi: 10.1111/jdi.13551. Epub 2021 May 20.
Prediabetes is a multifactorial condition. Current guidelines for diabetes screening recommend either the use of glycated hemoglobin (HbA1c), or blood glucose level (BGL). This research aimed to identify if p66shc a component of the Human SHC-Transforming Protein 1 (Shc1), a mitochondrial associated oxidative stress biomarker, is significantly altered in patients with elevated BGL. Furthermore, we evaluated if inflammatory and oxidative stress markers, such as p66shc, are a useful addition to the regularly used biomarkers to increase sensitivity for identification of prediabetes.
All participants attended the Diabetic Health Screening at Charles Sturt University (CSU), Australia. The cross-sectional clinical study collected demographic and clinical variables from 346 participants and classified into control or prediabetes based on fasting BGL. Blood and urine samples were analyzed for oxidative stress and inflammation markers. Logistic regression was used to compare multidimensional diagnostic models for prediabetes, including p66shc/Shc1, to the current HbA1c-only model in terms of sensitivity, specificity and predictive accuracy. Significance was set at P ≤ 0.05.
A significant decrease of p66shc/Shc1 was determined in prediabetes compared to controls (P ≤ 0.05). HbA1c testing resulted in an accuracy of 62%, while adding p66shc and triglycerides increased predictive accuracy to 88.05%. When HbA1c was omitted and Shc1 was combined with 8-hydroxy-2'-deoxyguanosine (8-OHdG) and monocyte chemo-attractant protein-1 (MCP-1), a predictive accuracy of 89.5% was achieved.
Our findings showed a major improvement of sensitivity to identify prediabetes by including oxidative stress and inflammatory biomarkers underlining beneficial diagnostic information, which most likely improves prevention and early treatment options in prediabetes.
前驱糖尿病是一种多因素疾病。目前的糖尿病筛查指南建议使用糖化血红蛋白（HbA1c）或血糖水平（BGL）。本研究旨在确定 p66shc 是否是人 SHC-转化蛋白 1（Shc1）的一个组成部分，Shc1 是一种与线粒体相关的氧化应激生物标志物，在血糖升高的患者中是否发生显著改变。此外，我们评估了 p66shc 等炎症和氧化应激标志物是否可作为常规使用的生物标志物的有益补充，以提高识别前驱糖尿病的敏感性。
所有参与者均参加了澳大利亚查尔斯·斯图尔特大学（CSU）的糖尿病健康筛查。这项横断面临床研究从 346 名参与者中收集了人口统计学和临床变量，并根据空腹 BGL 将其分类为对照组或前驱糖尿病组。分析了血液和尿液样本中的氧化应激和炎症标志物。使用逻辑回归比较了包括 p66shc/Shc1 在内的多维诊断模型与目前仅基于 HbA1c 的模型在预测前驱糖尿病方面的敏感性、特异性和预测准确性。P 值≤0.05 时认为差异有统计学意义。
与对照组相比，前驱糖尿病患者的 p66shc/Shc1 显著降低（P ≤ 0.05）。HbA1c 检测的准确率为 62%，而加入 p66shc 和三酰甘油可将预测准确率提高至 88.05%。当省略 HbA1c 并将 Shc1 与 8-羟基-2'-脱氧鸟苷（8-OHdG）和单核细胞趋化蛋白-1（MCP-1）联合使用时，可达到 89.5%的预测准确率。
我们的研究结果表明，通过纳入氧化应激和炎症生物标志物，可以显著提高识别前驱糖尿病的敏感性，这为前驱糖尿病提供了有益的诊断信息，很可能改善了前驱糖尿病的预防和早期治疗选择。
