Association of major candidate protein biomarkers and long-term diabetic kidney disease progression among Asians with young-onset type 2 diabetes mellitus

IF 6.1 3区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Tan Si Hua Clara , Zheng Huili , Liu Jian-Jun , Sylvia Liu , Lee Wei Lun Janus , Kee Kai Xiang , Resham Lal Gurung , M. Yiamunaa , Ang Kue Loong Keven , Shao Yi-Ming , Tavintharan Subramaniam , Sum Chee Fang , Lim Su Chi
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Abstract

Aims

We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM).

Methods

824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m2 or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays.

Results

Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44–2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68–0.76) to 0.74 (95 %CI 0.70–0.78), p = 0.099.

Conclusions

Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.

亚洲年轻 2 型糖尿病患者的主要候选蛋白生物标志物与糖尿病肾病长期进展的关系。
目的:我们旨在确定亚洲年轻2型糖尿病(T2DM)患者中7种主要候选蛋白生物标志物与糖尿病肾病(DKD)进展的关系。方法:根据每年估计肾小球滤过率(eGFR)比基线下降>3 ml/min/1.73 m2或>40%,将824名T2DM患者(发病年龄小于40岁)归类为DKD进展者。使用酶联免疫测定法测定了血浆富亮氨酸α-2-糖蛋白1(pLRG1)、肿瘤坏死因子受体1(pTNF-R1)、色素上皮衍生因子(pPEDF)、尿α-1-微球蛋白(uA1M)、肾损伤分子1(uKIM-1)、血红蛋白(uHP)和尿肌球蛋白(uUMOD):在5.7年的随访中,25.2%的患者病情恶化。pLRG1、pTNF-R1、pPEDF、uA1M、uKIM-1和uHP水平的升高与DKD进展有关。在对临床协变量进行调整后,pTNF-R1 水平与 DKD 进展之间的相关性仍然存在(OR 1.84,95 %CI 1.44-2.34,p 结论):在七种主要候选蛋白中,pTNF-R1部分通过高血糖和白蛋白尿介导,有力地预测了亚洲年轻T2DM患者的DKD进展。
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来源期刊
Diabetes research and clinical practice
Diabetes research and clinical practice 医学-内分泌学与代谢
CiteScore
10.30
自引率
3.90%
发文量
862
审稿时长
32 days
期刊介绍: Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.
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