Association of major candidate protein biomarkers and long-term diabetic kidney disease progression among Asians with young-onset type 2 diabetes mellitus
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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引用次数: 0
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.
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.