1 型糖尿病并发症中人类补体成分 C3 N-糖基化的变化。
Human complement component C3 N-glycome changes in type 1 diabetes complications.
机构信息
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
出版信息
Front Endocrinol (Lausanne). 2023 May 24;14:1101154. doi: 10.3389/fendo.2023.1101154. eCollection 2023.
AIM
Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors.
RESEARCH DESIGN AND METHODS
Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling.
RESULTS
Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration.
CONCLUSION
This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity.
目的
糖基化修饰的改变在许多疾病中都有描述，并被认为是疾病病理状态的生物标志物。先前的研究表明，N-糖基化与 1 型糖尿病（T1D）之间存在关联，特别是将血清 N-聚糖的变化与伴随疾病的并发症联系起来。此外，补体成分 C3 在糖尿病肾病和视网膜病变中的作用已被牵涉在内，并且在年轻的 T1D 患者中发现 C3 N-聚糖组发生改变。因此，我们研究了 C3 N-聚糖谱与 T1D 相关的蛋白尿和视网膜病变之间的关联，以及糖基化与其他已知的 T1D 并发症危险因素之间的关系。
研究设计和方法
从克罗地亚医院中心招募的 189 例 T1D 患者（中位年龄 46 岁）的 189 份血清样本中分析了补体成分 C3 N-糖基化谱。使用我们最近开发的高通量方法，确定了 C3 糖肽的所有六种相对丰度。使用线性模型评估 C3 N-聚糖与 T1D 并发症、高血压、吸烟状况、估算肾小球滤过率（eGFR）、血糖控制和疾病持续时间的相互关系。
结果
在伴有 1 型糖尿病的严重蛋白尿以及患有高血压的 T1D 患者中观察到 C3 N-聚糖谱的显著变化。除一种 C3 糖肽外，所有 C3 糖肽均与测量的 HbA1c 水平相关。一种糖型在非增生性 T1D 视网膜病变中发生改变。吸烟和 eGFR 对 C3 N-聚糖谱没有影响。此外，C3 N-糖基化谱与疾病持续时间无关。
结论
本研究增强了 C3 N-糖基化在 T1D 中的作用，表明其在区分不同糖尿病并发症患者方面具有价值。这些变化与疾病的发生有关，并且与疾病的持续时间无关，因此可能与疾病的进展和严重程度有关，使 C3 N-聚糖成为疾病进展和严重程度的潜在新型标志物。
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