School of Medical and Health Sciences, Edith Cowan University, 6027, WA, Australia.
Genos Glycoscience Research Laboratory, 10000, Zagreb, Croatia.
Arch Biochem Biophys. 2019 Jan;661:10-21. doi: 10.1016/j.abb.2018.10.015. Epub 2018 Oct 24.
Aberrant protein glycosylation may reflect changes in cell metabolism of type II diabetes mellitus (T2DM) and offers fresh vistas for discovering potential biomarkers. However, the functional significance of T2DM N-glycan alterations is underexplored, since to date, N-glycan profiling studies have been performed in selected populations. Geographically and genetically isolated populations are needed for validation of specific biomarkers. This age-sex matched cross sectional study comprising 232 T2DM patients and 219 controls was conducted in Ghana, Western Africa. Blood plasma samples were collected for clinical assessment after which plasma N-glycans were freed and analysed by ultra-performance liquid chromatography (UPLC). High branching (HB) [W = 46328; q = 0.00072], tri-galactosylated (G3) [W = 44076; q = 0.00096], antennary fucosylated (FUC_A) [W = 43055; q = 0.0000763], and triantennary (TRIA) [W = 44624; q = 0.0025], N-glycan structures were increased in T2DM whereas low branching (LB) [W = 46328; q = 0.00072], non-sialylated (S0) [W = 46929; q = 0.00292], monogalactosylation (G1) [W = 44091; q = 0.0000763], core fucosylation (FUC_C), [W = 46497; q = 0.00096], biantennary galactosylation (A2G) [W = 45663; q = 0.000763], and biantennary (BA) [W = 46376; q = 0.00072], structures were decreased compared to controls. Nine N-glycan peaks (GPs (GP1, GP4, GP7, GP11, GP17, GP19, GP22, GP26, GP29)) were found to predict case status based on Akaike's information criterion (AIC) and Bayesian information criterion (BIC) model selection. Adjusting for age, sex and other co-variates in this model yielded an area under the curve (AUC) of 80.5% with sensitivity of 79% and specificity of 73%, indicating the predicting power of N-glycans as robust biomarkers. Our results show that hyperglycemia influences N-glycan complexities among Ghanaians. N-glycan profiling in distinct populations has affirmed the potentiality of N-glycan profiles as generic biomarkers which may facilitate better prognosis for T2DM.
异常的蛋白质糖基化可能反映了 2 型糖尿病 (T2DM) 细胞代谢的变化，并为发现潜在的生物标志物提供了新的视角。然而，由于迄今为止，N-糖链谱分析研究仅在选定的人群中进行，因此 T2DM N-糖链改变的功能意义仍未得到充分探索。需要具有地理和遗传隔离的人群来验证特定生物标志物。这项在加纳进行的、年龄和性别匹配的横断面研究共纳入了 232 例 T2DM 患者和 219 名对照者。采集血液样本进行临床评估，然后释放血浆 N-糖并通过超高效液相色谱 (UPLC) 进行分析。在 T2DM 中，高分支 (HB) [W=46328; q=0.00072]、三半乳糖基化 (G3) [W=44076; q=0.00096]、触角岩藻糖化 (FUC_A) [W=43055; q=0.0000763] 和三触角 (TRIA) [W=44624; q=0.0025] 的 N-糖结构增加，而低分支 (LB) [W=46328; q=0.00072]、非唾液酸化 (S0) [W=46929; q=0.00292]、单半乳糖基化 (G1) [W=44091; q=0.0000763]、核心岩藻糖化 (FUC_C) [W=46497; q=0.00096]、双触角半乳糖基化 (A2G) [W=45663; q=0.000763] 和双触角 (BA) [W=46376; q=0.00072] 的结构与对照组相比有所减少。基于赤池信息量准则 (AIC) 和贝叶斯信息准则 (BIC) 模型选择，发现 9 个 N-糖峰 (GP(GP1、GP4、GP7、GP11、GP17、GP19、GP22、GP26、GP29)) 可用于预测病例状态。在该模型中，调整年龄、性别和其他协变量后，曲线下面积 (AUC) 为 80.5%，灵敏度为 79%，特异性为 73%，表明 N-糖作为稳健生物标志物的预测能力。我们的结果表明，高血糖会影响加纳人群的 N-糖复杂性。在不同人群中进行 N-糖谱分析证实了 N-糖谱作为通用生物标志物的潜力，这可能有助于改善 T2DM 的预后。
