Type 2 diabetes mellitus (T2DM) is a common complex trait arising from interactions among multiple environmental, genomic, and postgenomic factors. We report here the first attempt to investigate the association between immunoglobulin G (IgG) N-glycan patterns, T2DM, and their clinical risk factors in an Australian population. N-glycosylation of proteins is one of the most frequently observed co- and post-translational modifications, reflecting, importantly, the real-time status of the interplay between the genomic and postgenomic factors. In a community-based case-control study, 849 participants (217 cases and 632 controls) were recruited from an urban community in Busselton, Western Australia. We applied the ultraperformance liquid chromatography method to analyze the composition of IgG N-glycans. We then conducted Spearman's correlation analyses to explore the association between glycan biomarker candidates and clinical risk factors. We performed area under the curve (AUC) analysis of the receiver operating characteristic curves by fivefold cross-validation for clinical risk factors, IgG glycans, and their combination. Two directly measured and four derived glycan peaks were significantly associated with T2DM, after correction for extensive clinical confounders and false discovery rate, thus suggesting that IgG N-glycan traits are highly correlated with T2DM clinical risk factors. Moreover, adding the IgG glycan profiles to fasting blood glucose in the logistic regression model increased the AUC from 0.799 to 0.859. The AUC for IgG glycans alone was 0.623 with a 95% confidence interval 0.580-0.666. In addition, our study provided new evidence of diversity in T2DM complex trait by IgG N-glycan stratification. Six IgG glycan traits were firmly associated with T2DM, which reflects an increased proinflammatory and biological aging status. In summary, our study reports novel associations between the IgG N-glycome and T2DM in an Australian population and the putative role of proinflammatory mechanisms. Furthermore, IgG N-glycomic alterations offer future prospects as inflammatory biomarker candidates for T2DM diagnosis, and monitoring of T2DM progression to cardiovascular disease or renal failure.

中文翻译：

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2型糖尿病是通过澳大利亚人群的推定促炎机制与免疫球蛋白G N糖相关的。

2型糖尿病（T2DM）是一种常见的复杂性状，由多种环境，基因组和后基因组因素之间的相互作用引起。我们在这里报告的第一次尝试调查免疫球蛋白G（IgG）N糖模式，T2DM和其在澳大利亚人群中的临床危险因素之间的关联。蛋白质的N-糖基化是最常观察到的共翻译和翻译后修饰之一，重要地反映了基因组和后基因组之间相互作用的实时状态。在一项基于社区的病例对照研究中，从西澳大利亚州巴瑟尔顿的一个城市社区招募了849名参与者（217名病例和632名对照）。我们应用超高效液相色谱法分析了IgG N-聚糖的组成。然后我们进行了Spearman' 的相关性分析探讨了聚糖生物标志物候选物与临床危险因素之间的关联。通过对临床危险因素，IgG聚糖及其组合进行五重交叉验证，我们对接收器的工作特征曲线进行了曲线下面积（AUC）分析。在校正了广泛的临床混杂因素和错误发现率之后，两个直接测量的峰和四个衍生的聚糖峰与T2DM显着相关，因此表明IgG N-聚糖特征与T2DM临床危险因素高度相关。此外，在逻辑回归模型中将IgG聚糖谱添加到空腹血糖中，AUC从0.799增加到0.859。IgG聚糖的单独AUC为0.623，95％置信区间为0.580-0.666。此外，我们的研究通过IgG N-聚糖分层为T2DM复杂性状的多样性提供了新的证据。六个IgG聚糖特性与T2DM紧密相关，这反映了促炎和生物衰老状态的增加。总而言之，我们的研究报告了澳大利亚人群中IgG N-糖基团和T2DM之间的新型关联以及促炎机制的假定作用。此外，IgG N糖基化改变为T2DM诊断和监测T2DM演变为心血管疾病或肾衰竭的炎症生物标志物候选物提供了未来的前景。我们的研究报告了澳大利亚人群中IgG N-糖基团和T2DM之间的新型关联以及促炎机制的假定作用。此外，IgG N糖基化改变作为T2DM诊断和监测T2DM进展为心血管疾病或肾功能衰竭的炎性生物标志物候选物提供了未来的前景。我们的研究报告了澳大利亚人群中IgG N-糖基团和T2DM之间的新型关联以及促炎机制的假定作用。此外，IgG N糖基化改变作为T2DM诊断和监测T2DM进展为心血管疾病或肾功能衰竭的炎性生物标志物候选物提供了未来的前景。