Folkhälsan Research Center, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Cardiovasc Diabetol. 2024 Jul 4;23(1):235. doi: 10.1186/s12933-024-02316-w.
Despite improved glycemic treatment, the impact of glycation on pathological consequences may persist and contribute to adverse clinical outcomes in diabetes. In the present study we investigated the association between serum protein glycation products and progression of kidney disease as well as incident major adverse cardiovascular events (MACE) in type 1 diabetes.
Fructosamine, advanced glycation end products (AGEs), and methylglyoxal-modified hydro-imidazolone (MG-H1) were measured from baseline serum samples in the FinnDiane study (n = 575). Kidney disease progression was defined as steep eGFR decline (> 3 mL/min/1.73 m/year) or progression of albuminuria (from lower to higher stage of albuminuria). MACE was defined as acute myocardial infarction, coronary revascularization, cerebrovascular event (stroke), and cardiovascular death.
Fructosamine was independently associated with steep eGFR decline (OR 2.15 [95% CI 1.16-4.01], p = 0.016) in the fully adjusted model (age, sex, baseline eGFR). AGEs were associated with steep eGFR decline (OR 1.58 per 1 unit of SD [95% CI 1.07-2.32], p = 0.02), progression to end-stage kidney disease (ESKD) (HR 2.09 per 1 unit of SD [95% CI 1.43-3.05], p < 0.001), and pooled progression (to any stage of albuminuria) (HR 2.72 per 1 unit of SD [95% CI 2.04-3.62], p < 0.001). AGEs (HR 1.57 per 1 unit of SD [95% CI 1.23-2.00], p < 0.001) and MG-H1 (HR 4.99 [95% CI 0.98-25.55], p = 0.054) were associated with incident MACE. MG-H1 was also associated with pooled progression (HR 4.19 [95% CI 1.11-15.89], p = 0.035). Most AGEs and MG-H1 associations were no more significant after adjusting for baseline eGFR.
Overall, these findings suggest that protein glycation products are an important risk factor for target organ damage in type 1 diabetes. The data provide further support to investigate a potential causal role of serum protein glycation in the progression of diabetes complications.
尽管血糖控制得到改善，但糖化作用对病理后果的影响可能仍然存在，并导致 1 型糖尿病的不良临床结局。本研究旨在探讨血清蛋白糖化产物与 1 型糖尿病患者肾脏疾病进展以及主要不良心血管事件（MACE）发生之间的关系。
在 FinnDiane 研究中（n=575），从基线血清样本中测量果糖胺、晚期糖基化终产物（AGEs）和甲基乙二醛修饰的羟咪唑啉（MG-H1）。肾脏疾病进展定义为 eGFR 急剧下降（>3 mL/min/1.73 m/年）或蛋白尿进展（从较低阶段进展到较高阶段）。MACE 定义为急性心肌梗死、冠状动脉血运重建、脑血管事件（中风）和心血管死亡。
果糖胺在完全调整模型（年龄、性别、基线 eGFR）中与 eGFR 急剧下降独立相关（OR 2.15[95%CI 1.16-4.01]，p=0.016）。AGEs 与 eGFR 急剧下降（OR 1.58/SD 单位[95%CI 1.07-2.32]，p=0.02）、进展至终末期肾病（ESKD）（HR 2.09/SD 单位[95%CI 1.43-3.05]，p<0.001）和累积进展（任何阶段的蛋白尿）（HR 2.72/SD 单位[95%CI 2.04-3.62]，p<0.001）相关。AGEs（HR 1.57/SD 单位[95%CI 1.23-2.00]，p<0.001）和 MG-H1（HR 4.99[95%CI 0.98-25.55]，p=0.054）与 MACE 事件的发生相关。MG-H1 也与累积进展相关（HR 4.19[95%CI 1.11-15.89]，p=0.035）。在调整基线 eGFR 后，大多数 AGEs 和 MG-H1 相关性不再显著。
总的来说，这些发现表明，蛋白质糖化产物是 1 型糖尿病靶器官损伤的一个重要危险因素。这些数据进一步支持了研究血清蛋白糖化在糖尿病并发症进展中的潜在因果作用。
