N-Glycan Profile and Kidney Disease in Type 1 Diabetes
N-Glycan Profile and Kidney Disease in Type 1 Diabetes
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DOI：
10.2337/dc17-1042
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发表时间：
2018-01-01
期刊：
影响因子：
16.2
通讯作者：
Colhoun, Helen M.
中科院分区：
文献类型：
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作者：
Bermingham, Mairead L.;Colombo, Marco;Colhoun, Helen M.
结论1型糖尿病的药物血糖控制可能改变循环糖蛋白的N-糖基化模式，这些改变可能与糖尿病肾病（DKD）有关。我们调查了1型糖尿病患者N-聚糖与血糖控制和肾功能之间的关系。研究设计和方法使用来自818名被认为在估计肾小球滤过率（eGFR;即，基于回顾性临床记录，我们从苏格兰糖尿病研究网络1型生物资源研究的6，127名成年人中测量了总N-聚糖和IgG特异性N-聚糖谱。这产生了39个总（GP）和24个IgG（IGP）N-聚糖的相对丰度。使用线性回归模型研究N-聚糖结构与HbA（1c）、白蛋白/肌酐比值（ACR）和eGFR斜率之间的相关性。调整模型的年龄、性别、1型糖尿病病程和血清总IgG。HbA（1c）较高与简单双触角N-聚糖的相对丰度较低和具有更多分支、半乳糖基化和唾液酸化的更复杂结构的相对丰度较高相关（GP 12、26、31、32和34，以及IGP 19和23;所有P < 3.79 x 10（-4））。ACR和eGFR的年平均损失也有类似的模式，这也与更简单的N-聚糖减少有关（P < 3.79 × 10（-4））。结论1型糖尿病患者的HbA（1c）升高与血清N-糖组的变化有关，而血清N-糖组的变化在其他地方被证明可以调节表皮生长因子受体和转化生长因子途径，这些途径与DKD有关。此外，N-聚糖与ACR和eGFR斜率相关。这些数据表明，改变的N-聚糖在DKD中的作用值得进一步研究。
OBJECTIVEPoorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes.RESEARCH DESIGN AND METHODSUsing serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA(1c), albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.RESULTSHigher HbA(1c) was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 x 10(-4)). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 x 10(-4)).CONCLUSIONSHigher HbA(1c) in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor- pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.