Angiopoietin-like 4 is a potential biomarker for diabetic kidney disease in type 2 diabetes patients

IF 3.1 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2024-09-12 DOI:10.1111/jdi.14304

Yan Wang, Kun Li, Shasha Yuan, Caiguo Yu, Ruili Yin, Di Wang, Yongsong Xu, Lijie Zhang, Lingling Wei, Yanan Cheng, Lin Mao, Dong Zhao, Longyan Yang

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Abstract

Aims/Introduction

The association between serum angiopoietin-like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear.

Methods

A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross-sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable-adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression.

Results

Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P < 0.05). There was a negative nonlinear relationship between ANGPTL4 and estimated glomerular filtration rate in type 2 diabetes mellitus patients. One standard deviation increased serum ANGPTL4 levels, the odds ratio of having DKD was 1.40 (95% confidence interval 1.08–1.80). The mediation analysis showed that triglycerides did not mediate the association between ANGPTL4 and DKD. Furthermore, ANGPTL4 could be the strongest among multiple panels of biomarkers in its association of DKD. Compared with mice at 8 weeks-of-age, db/db mice at 18 weeks-of-age had increased ANGPTL4 expression in glomeruli and tubular segments. In vitro, glucose could stimulate ANGPTL4 expression in tubular cells in a dose-dependent manner.

Conclusions

ANGPTL4 could be a potential marker and therapeutic target for DKD treatment.

Abstract Image

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血管生成素样 4 是 2 型糖尿病患者糖尿病肾病的潜在生物标志物

这项横断面研究共分析了 1,115 名 2 型糖尿病患者，其血清血管生成素样 4（ANGPTL4）水平与糖尿病肾病（DKD）严重程度之间的关系仍不清楚。DKD指数包括以估计肾小球滤过率定义的DKD分期、白蛋白尿分级和DKD风险管理分级。研究还检测了血清中 ANGPTL4 和其他生物标记物的水平。采用多变量调整线性分析和逻辑分析来研究 ANGPTL4 与 DKD 之间的关系。对肾脏中的 ANGPTL4 蛋白水平进行了评估。结果与ANGPTL4处于第三或第四量级的参与者相比，ANGPTL4处于第一或第二量级的参与者更年轻，糖化血红蛋白、甘油三酯和尿白蛋白肌酐比值更低（均为P< 0.05）。2 型糖尿病患者的 ANGPTL4 与估计肾小球滤过率之间呈负非线性关系。血清ANGPTL4水平每增加一个标准差，患DKD的几率比为1.40（95%置信区间为1.08-1.80）。中介分析表明，甘油三酯并不中介 ANGPTL4 与 DKD 之间的关系。此外，ANGPTL4可能是多种生物标志物中与DKD关联性最强的一种。与8周龄的小鼠相比，18周龄的db/db小鼠在肾小球和肾小管节段的ANGPTL4表达增加。结论ANGPTL4可能是治疗DKD的潜在标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).