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Frontiers of Medicine

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Front. Med.    2020, Vol. 14 Issue (5) : 642-650    https://doi.org/10.1007/s11684-019-0719-3
RESEARCH ARTICLE
Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study
Huiwen Ren1,2, Can Wu3, Ying Shao4, Shuang Liu5, Yang Zhou1, Qiuyue Wang1()
1. Department of Endocrinology, the First Hospital of China Medical University, Shenyang 110001, China
2. Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China
3. Department of Gastroenterology and Endoscopy, the First Hospital of China Medical University, Shenyang 110001, China
4. Department of Endocrinology, the Second Hospital of China Medical University, Shenyang 110001, China
5. Severe Infection Intensive Care Unit, Affiliated Central Hospital of Shenyang Medical College, Shenyang 110001, China
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Abstract

This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease (DKD). A total of 390 patients with T2DM were divided into three groups: normal albuminuria (UACR<30 mg/g, n=136, NA), microalbuminuria (UACR at 30–300 mg/g, n=132, MA), and clinical albuminuria (UACR>300 mg/g, n=122, CA). Circulating miR-154-5p, inflammatory (C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); and tumor necrosis factor-α (TNF-α) and fibrotic markers (vascular endothelial growth factor (VEGF); transforming growth factor-β1 (TGF-β1); and fibronectin (FN)), and other biochemical indicators were assessed via real-time PCR, enzyme-linked immunosorbent assay, and chemiluminescence assay in patients with T2DM and 138 control subjects (NC). UACR, miR-154-5p, glycated hemoglobin (HbA1c), serum creatinine (sCr), blood urea nitrogen (BUN), ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were significantly higher and the estimated glomerular filtration rate (eGFR) was significantly lower in NA, MA, and CA groups than in NC subjects (P<0.05). Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c, sCr, BUN, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN and negatively correlated with eGFR (P<0.05). miR-154-5p, HbA1c, sCr, BUN, eGFR, ESR, CRP, VEGF, TNF-α, TGF-β1, and FN were important factors affecting UACR. These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.
Keywords type 2 diabetes mellitus      diabetic kidney disease      miR-154-5p      urinary albumin to creatinine ratio     
Corresponding Author(s): Qiuyue Wang   
Just Accepted Date: 30 December 2019   Online First Date: 17 January 2020    Issue Date: 12 October 2020
 Cite this article:   
Huiwen Ren,Can Wu,Ying Shao, et al. Correlation between serum miR-154-5p and urinary albumin excretion rates in patients with type 2 diabetes mellitus: a cross-sectional cohort study[J]. Front. Med., 2020, 14(5): 642-650.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0719-3
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I5/642
Fig.1  Flow chart of the cross-sectional study.
NC NA MA CA F/c2 P value
N (M/F) 138 (68/70) 136 (70/66) 132 (65/67) 122 (62/60) 2.165 0.539
Age (year) 56.20±11.01 55.96±10.83 54.98±10.00 55.77±10.39 0.330 0.804
Course (year) 0.00 (0.00–0.00) 0.00 (0.00–3.50)a 0.00 (0.00–6.25)a 0.00 (0.00–7.00)a 15.484 <0.001
SBP (mmHg) 114.87±8.41 115.42±8.59 115.61±8.79 114.19±8.58 0.700 0.554
DBP (mmHg) 68.48±5.83 70.59±5.73a 70.38±5.57a 69.77±5.84a 3.740 0.011
BMI (kg/m2) 25.97±3.24 25.80±2.91 26.50±3.35 25.38±3.19a 2.750 0.042
HOMA-IR 5.54 (2.55–8.51) 3.65 (1.99–6.10)a 3.67 (1.74–6.08)a 3.54 (1.27–6.52)a 16.340 <0.001
HbA1c (%) 5.12±1.13 8.17±2.25a 8.91±1.62ab 9.85±1.93abc 177.450 <0.001
HDL-C (mmol/L) 1.33±0.36 1.10±0.27a 1.07±0.41a 1.13±0.52a 11.890 <0.001
LDL-C (mmol/L) 2.72±0.81 3.10±1.09a 3.07±1.09a 3.19±1.03a 5.680 <0.001
TC (mmol/L) 4.34±1.16 4.81±1.24a 4.84±1.22a 5.05±1.51a 7.190 <0.001
TG (mmol/L) 1.13 (0.78–1.78) 1.46 (1.01–2.46)a 1.52 (1.08–2.41)a 1.47 (0.97–2.38)a 15.070 0.002
UA (mmol/L) 267.54±73.06 299.41±91.68a 300.11±89.31a 306.11±91.09a 5.470 0.001
sCr (mmol/L) 57.40±8.34 59.93±9.64a 62.53±10.60ab 68.21±9.17abc 30.620 <0.001
BUN (mmol/L) 4.81±1.03 4.94±0.91 5.92±0.84ab 6.33±1.05abc 78.560 <0.001
eGFR 125.24 (121.91–128.35) 117.72 (114.15–120.80)a 105.91 (102.44–108.31)ab 92.37 (89.53–94.18)abc 463.620 <0.001
UACR (mg/g) 9.66 (3.98–14.15) 11.05 (6.51–14.96) 95.63 (59.63–142.51)ab 579.05 (364.57–1473.33)abc 439.810 <0.001
*ESR (mmH2O) 6.00 (4.00–9.00) 9.00 (6.50–12.00)a 17.00 (13.00–22.00)ab 35.00 (26.00–44.00)abc 327.310 <0.001
CRP (mg/L) 3.76±1.30 5.41±1.32a 7.93±5.14ab 10.69±7.12abc 61.710 <0.001
miR-154-5p 0.47 (0.45–0.49) 0.64 (0.58–0.69)a 0.71 (0.66–0.75)ab 0.87 (0.82–0.96)abc 423.460 <0.001
VEGF (ng/L) 110.34±27.25 131.35±17.78a 146.55±22.03ab 182.76±20.76abc 241.150 <0.001
TNF-α (pg/mL) 28.36±0.97 44.34±2.12a 66.33±3.97ab 84.06±5.10abc 6849.150 <0.001
TGF-β1 (mg/L) 5.73±0.71 11.61±1.78a 13.52±3.24ab 18.98±1.95abc 871.830 <0.001
FN (ng/mL) 246.23±12.91 353.02±13.51a 481.90±14.60ab 610.05±19.96abc 13 682.520 <0.001
Tab.1  Levels of serum biomarkers and clinical characteristics in the studied groups
　 Ln miR-154-5p
r P
HbA1c 0.204 <0.001
sCr 0.272 <0.001
BUN 0.345 <0.001
Ln eGFR −0.740 <0.001
Ln UACR 0.678 <0.001
Ln ESR 0.576 <0.001
CRP 0.291 <0.001
VEGF 0.567 <0.001
TNF-α 0.714 <0.001
TGF-β1 0.584 <0.001
FN 0.731 <0.001
Tab.2  Correlation between miR-154-5p and other clinical parameters in patients with T2DM
　 Ln UACR
r P
Ln miR-154-5p 0.678 <0.001
HbA1c 0.304 <0.001
sCr 0.343 <0.001
BUN 0.477 <0.001
Ln eGFR −0.846 <0.001
Ln ESR 0.681 <0.001
CRP 0.399 <0.001
VEGF 0.638 <0.001
TNF-α 0.887 <0.001
TGF-β1 0.701 <0.001
FN 0.900 <0.001
Tab.3  Correlation between UACR and clinical parameters in patients with T2DM
Fig.2  Ridge trace curve of the association between the clinical parameters and Ln UACR. y= Ln UACR as dependent variables and x1−x11 referred to HbA1c, CRP, sCr, BUN, VEGF, TNF-α, TGF-β1, Ln miR-154-5p, Ln eGFR, Ln ESR, and FN as independent variables.
　 Ln UACR
B Standard error Standard regression coefficient t P 95% CI
Constant 8.545 1.019 − 8.384 <0.001 (6.547, 10.543)
Ln miR-154-5p 0.873 0.180 0.074 4.856 <0.001 (0.521, 1.226)
HbA1c 0.034 0.015 0.034 2.214 0.027 (0.004, 0.064)
sCr 0.012 0.003 0.061 4.032 <0.001 (0.006, 0.018)
BUN 0.100 0.029 0.053 3.445 0.001 (0.043, 0.156)
Ln eGFR −2.277 0.190 −0.147 −11.985 <0.001 (−2.649, −1.904)
Ln ESR 0.254 0.043 0.091 5.949 <0.001 (0.171, 0.338)
CRP 0.020 0.006 0.054 3.531 <0.001 (0.009, 0.032)
VEGF 0.002 0.001 0.033 2.227 0.027 (0.000, 0.004)
TNF-α 0.023 0.001 0.189 20.317 <0.001 (0.021, 0.026)
TGF-β1 0.043 0.008 0.082 5.436 <0.001 (0.028, 0.059)
FN 0.004 0.000 0.201 19.859 <0.001 (0.004, 0.004)
Tab.4  Ridge regression analysis of UACR and clinical parameters among patients with T2DM
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