Introduction Prediction of type 2 diabetes mellitus (T2DM) and its preceding factors, such as insulin resistance (IR), is of great importance as it may allow delay or prevention of onset of the disease. Plasma protein N-glycome has emerged as a promising predictive biomarker. In a prospective longitudinal study, we included patients with a first diagnosis of impaired glucose metabolism (IR or T2DM) to investigate the N-glycosylation’s predictive value years before diabetes development. Research design and methods Plasma protein N-glycome was profiled by hydrophilic interaction ultra-performance liquid chromatography in 534 TwinsUK participants free from disease at baseline. This included 89 participants with incident diagnosis of IR or T2DM during the follow-up period (7.14±3.04 years) whose last sample prior to diagnosis was compared using general linear regression with 445 age-matched unrelated controls. Findings were replicated in an independent cohort. Changes in N-glycome have also been presented in connection with time to diagnosis. Results Eight groups of plasma N-glycans were different between incident IR or T2DM cases and controls (p<0.05) after adjusting for multiple testing using Benjamini-Hochberg correction. These differences were noticeable up to 10 years prior to diagnosis and are changing continuously as becoming more expressed toward the diagnosis. The prediction model was built using significant glycan traits, displaying a discriminative performance with an area under the receiver operating characteristic curve of 0.77. Conclusions In addition to previous studies, we showed the diagnostic potential of plasma N-glycome in the prediction of both IR and T2DM development years before the clinical manifestation and indicated the continuous deterioration of N-glycome toward the diagnosis. Data are available upon reasonable request.

中文翻译：

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随着胰岛素抵抗诊断的临近，血浆 N-糖组显示持续恶化

简介 预测 2 型糖尿病 (T2DM) 及其先前的因素，如胰岛素抵抗 (IR)，非常重要，因为它可以延迟或预防疾病的发作。血浆蛋白 N-糖组已成为一种有前途的预测生物标志物。在一项前瞻性纵向研究中，我们纳入了首次诊断为糖代谢受损（IR 或 T2DM）的患者，以研究糖尿病发展前几年 N-糖基化的预测价值。研究设计和方法 血浆蛋白 N-糖组通过亲水相互作用超高效液相色谱法对 534 名基线时无疾病的 TwinsUK 参与者进行了分析。这包括 89 名在随访期间被诊断为 IR 或 T2DM 的参与者（7.14±3. 04 年），其诊断前的最后一个样本使用一般线性回归与 445 名年龄匹配的无关对照进行比较。研究结果在一个独立的队列中重复。N-糖组的变化也与诊断时间有关。结果 在使用 Benjamini-Hochberg 校正对多重测试进行调整后，8 组血浆 N-聚糖在 IR 或 T2DM 病例与对照组之间存在差异 (p<0.05)。这些差异在诊断前 10 年就很明显，并且随着对诊断的表达越来越多，这些差异也在不断变化。预测模型是使用显着的聚糖性状建立的，显示出判别性能，接受者操作特征曲线下的面积为 0.77。结论 除了以前的研究，我们展示了血浆 N-糖组在临床表现前几年预测 IR 和 T2DM 发展的诊断潜力，并表明 N-糖组对诊断的持续恶化。可根据合理要求提供数据。