Clinical Research Unit, Khoo Teck Puat Hospital, Singapore; Cardiovascular and Metabolic Disorders Signature Research Program, Duke-NUS Medical School, Singapore.
Clinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Diabetes Res Clin Pract. 2024 Aug;214:111790. doi: 10.1016/j.diabres.2024.111790. Epub 2024 Jul 25.
Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications.
1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications.
Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline.
Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms.
在多民族亚洲人群中，2 型糖尿病（T2D）分为三种亚型；轻度肥胖相关糖尿病（MOD）、轻度年龄相关伴胰岛素不足的糖尿病（MARD-II）和严重胰岛素抵抗伴相对胰岛素不足的糖尿病（SIRD-RII），它们具有不同的心血管和肾脏并发症风险。我们评估了蛋白质组学特征，以确定亚型特异性生物标志物及其与糖尿病并发症的关系。
在基线时测量了 1448 种血浆蛋白，并在 T2D 亚型之间进行了比较。多变量 Cox 回归用于评估显著蛋白质组学特征与心血管和肾脏并发症之间的关联。
在 645 名 T2D 参与者中（SIRD-RII[19%]、MOD[45%]、MARD-II[36%]），有 295 种蛋白质的表达在各组之间存在显著差异。这些蛋白质在细胞黏附、神经发生和炎症反应过程中富集。在 SIRD-RII 组中，ADH4、ACY1、THOP1、IGFBP2、NEFL、ENTPD2、CALB1、HAO1、CTSV、ITGAV、SCLY、EDA2R、ERBB2 蛋白与进行性 CKD 显著相关，LILRA5 蛋白与新发心力衰竭（HF）显著相关。在 MOD 组中，TAFA5、RSPO3、EDA2R 蛋白与新发 HF 显著相关。在 MARD-II 组中，FABP4 蛋白与进行性 CKD 显著相关，PTPRN2 蛋白与主要不良心血管事件显著相关。遗传决定的 NEFL 和 CALB1 与肾功能下降相关。
每种 T2D 亚型都有独特的蛋白质组学特征，与临床结局和潜在机制相关。
