Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Diabetes Metab Res Rev. 2022 Sep;38(6):e3554. doi: 10.1002/dmrr.3554. Epub 2022 Jun 17.
12(S)-hydroxyeicosatetraenoic (12(S)-HETE), an alternate arachidonic acid metabolite, has been recently examined in metabolic disease. However, the role of 12(S)-HETE in diabetic kidney disease (DKD) remains unclear. We studied for the first time the relationship of serum 12(S)-HETE and DKD and renal function parameters in a Chinese population.
We recruited 275 subjects who were diagnosed with type 2 diabetes (T2DM) for more than 10 years, including 149 DKD patients and 126 T2DM patients without DKD. Serum 12(S)-HETE was measured using the enzyme-linked immunosorbent assay.
Serum 12(S)-HETE was significantly higher in DKD patients than controls [384.69 (77.54, 1003.05) pg/ml and 17.77 (8.11, 75.13) pg/ml, respectively, p < 0.0001]. Compared to controls, 12(S)-HETE was significantly increased in both macroalbuminuria and microalbuminuria groups (p < 0.0001). Further, the macroalbuminuria group also had a higher serum 12(S)-HETE level compared to the microalbuminuria group (p = 0.0063). Moreover, serum 12(S)-HETE was positively correlated with the albuminuria level (r = 0.5833, p < 0.0001), serum creatinine (r = 0.2725, p < 0.0001), and was negatively associated with the estimated glomerular filtration rate (r = -0.2085, p = 0.0005). Further, receiver operating characteristic analysis (ROC) revealed that 12(S)-HETE had a good performance of distinguishing DKD from controls (AUC 0.828) with a sensitivity of 0.913 and a specificity of 0.711.
Our findings revealed that serum 12(S)-HETE significantly associated with DKD and disease severity, suggesting that serum 12(S)-HETE may be used as a potential biomarker for the early diagnosis of DKD.
12(S)-羟基二十碳四烯酸（12(S)-HETE）是一种替代的花生四烯酸代谢物，最近在代谢疾病中进行了研究。然而，12(S)-HETE 在糖尿病肾病（DKD）中的作用仍不清楚。我们首次在中国人群中研究了血清 12(S)-HETE 与 DKD 及肾功能参数的关系。
我们招募了 275 名患有 2 型糖尿病（T2DM）超过 10 年的患者，其中 149 名 DKD 患者和 126 名无 DKD 的 T2DM 患者。使用酶联免疫吸附试验测量血清 12(S)-HETE。
与对照组相比，DKD 患者的血清 12(S)-HETE 水平显著升高[384.69（77.54，1003.05）pg/ml 和 17.77（8.11，75.13）pg/ml，p<0.0001]。与对照组相比，白蛋白尿组和微量白蛋白尿组的 12(S)-HETE 水平均显著升高（p<0.0001）。此外，白蛋白尿组的血清 12(S)-HETE 水平也高于微量白蛋白尿组（p=0.0063）。此外，血清 12(S)-HETE 与蛋白尿水平呈正相关（r=0.5833，p<0.0001），与血清肌酐呈正相关（r=0.2725，p<0.0001），与估计肾小球滤过率呈负相关（r=-0.2085，p=0.0005）。进一步的受试者工作特征分析（ROC）显示，12(S)-HETE 对区分 DKD 与对照组具有良好的性能（AUC 0.828），其敏感性为 0.913，特异性为 0.711。
我们的研究结果表明，血清 12(S)-HETE 与 DKD 及其严重程度显著相关，提示血清 12(S)-HETE 可作为 DKD 早期诊断的潜在生物标志物。
