Diabetes Care ( IF 14.8 ) Pub Date : 2018-01-01 , DOI: 10.2337/dc17-1042 Mairead L Bermingham 1 , Marco Colombo 2 , Stuart J McGurnaghan 1 , Luke A K Blackbourn 1 , Frano Vučković 3 , Maja Pučić Baković 3 , Irena Trbojević-Akmačić 3 , Gordan Lauc 3 , Felix Agakov 4 , Anna S Agakova 4 , Caroline Hayward 5 , Lucija Klarić 2, 5 , Colin N A Palmer 6 , John R Petrie 7 , John Chalmers 8 , Andrew Collier 9 , Fiona Green 10 , Robert S Lindsay 7 , Sandra Macrury 11 , John A McKnight 12 , Alan W Patrick 13 , Sandeep Thekkepat 14 , Olga Gornik 15 , Paul M McKeigue 2, 4 , Helen M Colhoun 1, 16 ,
OBJECTIVE Poorer 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 METHODS Using 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 HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.
RESULTS Higher HbA1c 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 × 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 × 10−4).
CONCLUSIONS Higher HbA1c 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-β 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.
中文翻译：
1 型糖尿病中的 N-聚糖谱和肾脏疾病
目的1 型糖尿病患者较差的血糖控制可能会改变循环糖蛋白的 N-糖基化模式，而这些改变可能与糖尿病肾病 (DKD) 有关。我们研究了 N-聚糖与 1 型糖尿病患者的血糖控制和肾功能之间的关联。
研究设计和方法使用来自苏格兰糖尿病研究网络 1 型生物资源研究中 6,127 名成年人的回顾性临床记录，估计肾小球滤过率（eGFR；即斜率）每年有极端损失的 818 名成年人的血清样本，我们测量了总的和 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。线性回归模型用于研究 N-聚糖结构与 HbA 1c、白蛋白肌酐比值 (ACR) 和 eGFR 斜率之间的关联。模型根据年龄、性别、1 型糖尿病持续时间和总血清 IgG 进行了调整。
结果较高的 HbA 1c与简单双触角 N-聚糖的相对丰度较低以及具有更多分支、半乳糖基化和唾液酸化（GP12、26、31、32 和 34，以及 IGP19 和 23）的更复杂结构的相对丰度较高相关; 所有P < 3.79 × 10 -4 )。ACR 和更大的 eGFR 年平均损失也有类似的模式，这也与较少的更简单的 N-聚糖相关（所有P < 3.79 × 10 -4）。
结论1 型糖尿病中较高的 HbA 1c与血清 N-糖组的变化相关，在其他地方已证明这种变化可调节与 DKD 相关的表皮生长因子受体和转化生长因子-β 通路。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。
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