Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, The Netherlands; Department of Internal Medicine, Maxima Medical Center, Eindhoven, The Netherlands.
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
Biochim Biophys Acta Gen Subj. 2017 Sep;1861(9):2240-2249. doi: 10.1016/j.bbagen.2017.06.020. Epub 2017 Jun 28.
Type 2 diabetes results from interplay between genetic and acquired factors. Glycans on proteins reflect genetic, metabolic and environmental factors. However, associations of IgG glycans with type 2 diabetes have not been described. We compared IgG N-glycan patterns in type 2 diabetes with healthy subjects.
In the DiaGene study, a population-based case-control study, (1886 cases and 854 controls) 58 IgG glycan traits were analyzed. Findings were replicated in the population-based CROATIA-Korcula-CROATIA-Vis-ORCADES studies (162 cases and 3162 controls), and meta-analyzed. AUCs of ROC-curves were calculated using 10-fold cross-validation for clinical characteristics, IgG glycans and their combination.
After correction for extensive clinical covariates, 5 IgG glycans and 13 derived traits significantly associated with type 2 diabetes in meta-analysis (after Bonferroni correction). Adding IgG glycans to age and sex increased the AUC from 0.542 to 0.734. Adding them to the extensive model did not substantially improve the AUC. The AUC for IgG glycans alone was 0.729.
Several IgG glycans and traits firmly associate with type 2 diabetes, reflecting a pro-inflammatory and biologically-aged state. IgG glycans showed limited improvement of AUCs. However, IgG glycans showed good prediction alone, indicating they may capture information of combined covariates. The associations found may yield insights in type 2 diabetes pathophysiology.
This work shows that IgG glycomic changes have biomarker potential and may yield important insights into pathophysiology of complex public health diseases, illustrated here for the first time in type 2 diabetes.
2 型糖尿病是由遗传和后天因素相互作用引起的。蛋白质上的聚糖反映了遗传、代谢和环境因素。然而，尚未描述 IgG 聚糖与 2 型糖尿病的关联。我们比较了 2 型糖尿病患者和健康对照者的 IgG N-糖型模式。
在 DiaGene 研究中，这是一项基于人群的病例对照研究，共分析了 1886 例病例和 854 例对照的 58 种 IgG 聚糖特征。在基于人群的 CROATIA-Korcula-CROATIA-Vis-ORCADES 研究中对这些发现进行了复制和荟萃分析（162 例病例和 3162 例对照），并进行了荟萃分析。使用 10 倍交叉验证计算了临床特征、IgG 聚糖及其组合的 ROC 曲线 AUC。
在对广泛的临床协变量进行校正后，荟萃分析显示，5 种 IgG 聚糖和 13 种衍生特征与 2 型糖尿病显著相关（经 Bonferroni 校正）。将 IgG 聚糖与年龄和性别相加，AUC 从 0.542 增加到 0.734。将其添加到广泛的模型中并不会显著提高 AUC。单独 IgG 聚糖的 AUC 为 0.729。
几种 IgG 聚糖和特征与 2 型糖尿病密切相关，反映了一种促炎和生物学老化状态。IgG 聚糖对 AUC 的改善有限。然而，单独 IgG 聚糖的预测性能良好，表明它们可能捕捉到了综合协变量的信息。所发现的关联可能为 2 型糖尿病的病理生理学提供深入了解。
这项工作表明 IgG 聚糖变化具有生物标志物潜力，并可能为复杂的公共卫生疾病的病理生理学提供重要见解，在本研究中首次在 2 型糖尿病中得到了证明。
