Metrnl and NLRP3 Inflammasome: Potential diagnostic biomarkers for diabetic kidney disease

doi:10.3877/cma.j.issn.2095-9605.2024.03.006

Abstract

Abstract:

Objective

This study aims to clarify the expression levels of Meteorin-like Protein (Metrnl) in patients with diabetic kidney disease (DKD) and to explore its potential association with NLRP3 inflammasome activity.

Methods

130 patients with type 2 diabetes Mellitus (T2DM) were enrolled at the Affiliated Hospital of Yan'an University between May 2020 and May 2022. Additionally, 45 healthy individuals served as a control group. The concentrations of Meteorin-like Protein (Metrnl) and NLRP3 inflammasome in the serum of participants were measured using the enzyme-linked immunosorbent assay (ELISA). Based on the urinary albumin-to-creatinine ratio (uACR), T2DM patients were categorized into a simple T2DM group and a Diabetic Kidney Disease (DKD) group. The serum levels of Metrnl and NLRP3 were compared between the two groups, and the correlation of these markers with other clinical characteristics in DKD patients was analyzed.

Results

Serum levels of Meteorin-like Protein (Metrnl) and NLRP3 were significantly higher in both the T2DM and DKD groups compared to the control group, with levels increasing by the severity of DKD (P<0.05). Additionally, serum Metrnl levels showed positive correlations with disease duration, waist circumference, systolic blood pressure, diastolic blood pressure, creatinine (Cr), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), urinary albumin-to-creatinine ratio (uACR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), DKD, and NLRP3. In contrast, a significant negative correlation existed between the estimated glomerular filtration rate (eGFR) and high-density lipoprotein cholesterol (HDL-C). Multivariate logistic regression analysis suggested that serum levels of Metrnl and NLRP3 may be associated with T2DM and DKD. Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) for serum Metrnl, NLRP3, and their combination in predicting DKD in T2DM patients were 0.9, 0.987, and 0.949, respectively, with NLRP3 exhibiting superior predictive value for DKD.

Conclusions

Serum levels of Metrnl and NLRP3 have the potential to serve as biomarkers for the early diagnosis and monitoring of DKD.

Key words: Type 2 diabetes mellitus, Diabetic kidney disease, Meteorin-like hormone (Metrnl), NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)

Mei Zhang, Hui Chen, Zhuanxia Li, Rui Wang, Linjuan Li. Metrnl and NLRP3 Inflammasome: Potential diagnostic biomarkers for diabetic kidney disease[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2024, 10(03): 193-199.

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References 20

[1]	Xue R, Gui D, Zheng L, et al. Mechanistic insight and management of diabetic nephropathy: Recent progress and future perspective [J]. J Diabetes Res, 2017, 2017: 1839809.
[2]	Liu L, Shi Z, Ji X, et al. Adipokines, adiposity, and atherosclerosis [J]. Cell Mol Life Sci, 2022, 79(5): 272.
[3]	Zhu X, Zhang HW, Chen HN, et al. Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway [J]. Acta Pharmacol Sin, 2019, 40(1): 46-54.
[4]	Wang K, Li F, Wang C, et al. Serum levels of meteorin-like (Metrnl) are increased in patients with newly diagnosed type 2 diabetes mellitus and are associated with insulin resistance [J]. Med Sci Monit, 2019, 25: 2337-2343.
[5]	林佳颖, 陈频, 徐向进, 等. 2型糖尿病患者血清脂肪分泌因子Metrnl水平与糖尿病肾病的相关性分析 [J]. 中华糖尿病杂志, 2021, 13(7): 708-712.
[6]	Wang R, Hu D, Zhao X, et al. Correlation of serum meteorin-like concentrations with diabetic nephropathy [J]. Diabetes Res Clin Pract, 2020, 169: 108443.
[7]	Chen J, Li ZY, Xu F. Low levels of Metrnl are linked to the deterioration of diabetic kidney disease [J]. Diabetes Metab Syndr Obes, 2024, 17: 959-967.
[8]	Anand PK. Lipids, inflammasomes, metabolism, and disease [J]. Immunol Rev, 2020, 297(1): 108-122.
[9]	中华医学会肾脏病学分会专家组. 糖尿病肾脏疾病临床诊疗中国指南 [J]. 中华肾脏病杂志, 2021, 37(3): 255-304.
[10]	Zhou Y, Liu L, Jin B, et al. Metrnl alleviates lipid accumulation by modulating mitochondrial homeostasis in diabetic nephropathy [J]. Diabetes, 2023, 72(5): 611-626.
[11]	Miao ZW, Hu WJ, Li ZY, et al. Involvement of the secreted protein Metrnl in human diseases [J]. Acta Pharmacol Sin, 2020, 41(12): 1525-1530.
[12]	Liu ZX, Ji HH, Yao MP, et al. Serum Metrnl is associated with the presence and severity of coronary artery disease [J]. J Cell Mol Med, 2019, 23(1): 271-280.
[13]	Chung HS, Hwang SY, Choi JH, et al. Implications of circulating Meteorin-like (Metrnl) level in human subjects with type 2 diabetes [J]. Diabetes Res Clin Pract, 2018, 136: 100-107.
[14]	Onalan E, Cavli C, Dogan Y, et al. Low serum levels of meteorin-like/subfatin: an indicator of diabetes mellitus and insulin resistance? [J]. Endokrynol Pol, 2020,7 1(5): 397-403.
[15]	Yang M, Wang X, Han Y, et al. Targeting the NLRP3 inflammasome in diabetic nephropathy [J]. Curr Med Chem, 2021, 28(42): 8810-8824.
[16]	Yuan Y, Li L, Wang X, et al. Correlation between plasma NLRP3, IL-1beta, and IL-18 and diabetic nephropathy in patients with type 2 diabetes [J]. Altern Ther Health Med, 2023, 29(4): 52-56.
[17]	Wu M, Yang Z, Zhang C, et al. Inhibition of NLRP3 inflammasome ameliorates podocyte damage by suppressing lipid accumulation in diabetic nephropathy [J]. Metabolism, 2021, 118: 154748.
[18]	Pan Y, Liu L, Yang H, et al. Sacubitril/valsartan improves progression of early diabetic nephropathy in rats through inhibition of NLRP3 inflammasome pathway [J]. Diabetes Metab Syndr Obes, 2022, 15: 2479-2488.
[19]	Yang M, Zhao L. The selective NLRP3-inflammasome inhibitor CY-09 ameliorates kidney injury in diabetic nephropathy by inhibiting NLRP3-inflammasome activation [J]. Curr Med Chem, 2023, 30(28): 3261-3270.
[20]	Javaid H, Sahar NE, Zhuge DL, et al. Exercise inhibits NLRP3 inflammasome activation in obese mice via the anti-inflammatory effect of meteorin-like [J]. Cells, 2021, 10(12): 3480.

指标	Control组	T2DM组	DKD组	χ²/F/H	P
例（男/女）	45（26/19）	50（34/16）	80（51/29）	0.53	0.589
年龄（岁）	52.71±10.48	52.98±9.37	56.28±10.39	2.48	0.086
BMI（kg/m²）[M（P25，P75）]	22.86（21.99，23.51）	23.00（21.50，24.20）	23.4（21.78，24.40）	2.49	0.139
腰围（cm）	80.6±8.44	86.0±7.44^a	87.98±10.77	9.08	<0.001
糖尿病病程（年）[M（P25，P75）]	—	3（2，8）	12（8，20）b	127.05	<0.001
收缩压（mmHg）[M（P25，P75）]	120（120，130）	130（130，148）^a	134（134，147）^a	14.50	0.001
舒张压（mmHg）	80（75，80）	80（70，90）	80（74，89.5）	3.56	0.116
FPG（mmol/L）	5.05±0.66	6.70±1.33^a	10.46±3.22^ab	89.02	<0.001
HbA1c（%）[M（P25，P75）]	5.00（4.6，5.4）	6.50（6.28，6.93）^a	9.75（8.35，11.2）^ab	131.43	<0.001
TG（mmol/L）[M（P25，P75）]	4.53（3.75，5.05）	2.49（1.73，4.04）	2.91（1.86，4.2）	5.53	0.555
TC (mmol/L)	4.38±0.97	2.85±1.37^a	3.00±1.39^a	20.81	<0.001
HDL-C(mmol/L)	1.28±0.61	1.22±0.84^a	1.19±0.76^a	0.19	0.834
LDL-C (mmol/L)	2.27±0.86	1.84±0.80	1.97±0.89^a	3.65	0.028
AST（U/L）	20.60±7.40	21.82±9.78	23.08±10.61	0.136	0.380
ALT（U/L）	22.11±17.30	23.78±16.30	23.34±16.32	0.97	0.878
CR（μmol/L）[M（P25，P75）]	58.00（51.9，67.8）	58.35（51.7，65.08）	92.75（78，118.88）^ab	99.13	<0.001
UA（μmol/L）	274.36±85.05	267.91±92.72	298.89±95.96	2.04	0.133
uACR（mg/g）[M（P25，P75）]	7.50（6.1，6.5）	8.72（6.18，11.16）	276.95（76.53，687.31）^ab	130.11	<0.001
eGFR (mL/min/1.73m2) [M（P25，P75）]	116.35（106.51，127.44）	124.31（114.27，134.7）	73.50（51.29，86.12）^ab	109.70	<0.001
Metrnl（pg/mL） [M（P25，P75）]	562.26（494.57，601.69）	763.04（670.06，839.53）^a	982.94（805.63，1227.97）^ab	108.63	<0.001
NLRP3（pg/mL）[M（P25，P75）]	173.05（164.63，180.80）	179.69（173.58，187.56）^a	213.4（203.57，224.86）^ab	127.58	<0.001

指标	Control组	T2DM组	DKD组	χ²/F/H	P
例（男/女）	45（26/19）	50（34/16）	80（51/29）	0.53	0.589
年龄（岁）	52.71±10.48	52.98±9.37	56.28±10.39	2.48	0.086
BMI（kg/m²）[M（P25，P75）]	22.86（21.99，23.51）	23.00（21.50，24.20）	23.4（21.78，24.40）	2.49	0.139
腰围（cm）	80.6±8.44	86.0±7.44^a	87.98±10.77	9.08	<0.001
糖尿病病程（年）[M（P25，P75）]	—	3（2，8）	12（8，20）b	127.05	<0.001
收缩压（mmHg）[M（P25，P75）]	120（120，130）	130（130，148）^a	134（134，147）^a	14.50	0.001
舒张压（mmHg）	80（75，80）	80（70，90）	80（74，89.5）	3.56	0.116
FPG（mmol/L）	5.05±0.66	6.70±1.33^a	10.46±3.22^ab	89.02	<0.001
HbA1c（%）[M（P25，P75）]	5.00（4.6，5.4）	6.50（6.28，6.93）^a	9.75（8.35，11.2）^ab	131.43	<0.001
TG（mmol/L）[M（P25，P75）]	4.53（3.75，5.05）	2.49（1.73，4.04）	2.91（1.86，4.2）	5.53	0.555
TC (mmol/L)	4.38±0.97	2.85±1.37^a	3.00±1.39^a	20.81	<0.001
HDL-C(mmol/L)	1.28±0.61	1.22±0.84^a	1.19±0.76^a	0.19	0.834
LDL-C (mmol/L)	2.27±0.86	1.84±0.80	1.97±0.89^a	3.65	0.028
AST（U/L）	20.60±7.40	21.82±9.78	23.08±10.61	0.136	0.380
ALT（U/L）	22.11±17.30	23.78±16.30	23.34±16.32	0.97	0.878
CR（μmol/L）[M（P25，P75）]	58.00（51.9，67.8）	58.35（51.7，65.08）	92.75（78，118.88）^ab	99.13	<0.001
UA（μmol/L）	274.36±85.05	267.91±92.72	298.89±95.96	2.04	0.133
uACR（mg/g）[M（P25，P75）]	7.50（6.1，6.5）	8.72（6.18，11.16）	276.95（76.53，687.31）^ab	130.11	<0.001
eGFR (mL/min/1.73m2) [M（P25，P75）]	116.35（106.51，127.44）	124.31（114.27，134.7）	73.50（51.29，86.12）^ab	109.70	<0.001
Metrnl（pg/mL） [M（P25，P75）]	562.26（494.57，601.69）	763.04（670.06，839.53）^a	982.94（805.63，1227.97）^ab	108.63	<0.001
NLRP3（pg/mL）[M（P25，P75）]	173.05（164.63，180.80）	179.69（173.58，187.56）^a	213.4（203.57，224.86）^ab	127.58	<0.001

项目	NLRP3		Metrnl
项目	Coefficient (r)	P value	Coefficient (r)	P value
性别	0.011	0.884	-0.031	0.686
年龄	0.083	0.274	0.151	0.046
糖尿病病史	0.666	<0.001	0.749	<0.001
腰围	0.174	0.021	0.251	0.001
BMI	0.082	0.284	0.13	0.086
收缩压	0.28	<0.001	0.325	<0.001
舒张压	0.196	0.009	0.19	0.012
AST	0.04	0.603	-0.02	0.798
ALT	0.082	0.279	0.055	0.473
CR	0.697	<0.001	0.601	<0.001
UA	0.121	0.112	0.149	0.049
uACR	0.766	<0.001	0.741	<0.001
eGFR	-0.686	<0.001	-0.582	<0.001
FPG	0.681	<0.001	0.617	<0.001
HbA1c	0.721	<0.001	0.693	<0.001
TG	0.005	0.944	-0.04	0.601
TC	0.18	0.017	0.256	0.001
HDL-C	-0.218	0.004	-0.217	0.004
LDL-C	0.175	0.021	0.183	0.015
NLRP3	1	—	0.757	<0.001
Metrnl	0.757	<0.001	1	—
DKD	0.841	<0.001	0.784	<0.001

项目	NLRP3		Metrnl
项目	Coefficient (r)	P value	Coefficient (r)	P value
性别	0.011	0.884	-0.031	0.686
年龄	0.083	0.274	0.151	0.046
糖尿病病史	0.666	<0.001	0.749	<0.001
腰围	0.174	0.021	0.251	0.001
BMI	0.082	0.284	0.13	0.086
收缩压	0.28	<0.001	0.325	<0.001
舒张压	0.196	0.009	0.19	0.012
AST	0.04	0.603	-0.02	0.798
ALT	0.082	0.279	0.055	0.473
CR	0.697	<0.001	0.601	<0.001
UA	0.121	0.112	0.149	0.049
uACR	0.766	<0.001	0.741	<0.001
eGFR	-0.686	<0.001	-0.582	<0.001
FPG	0.681	<0.001	0.617	<0.001
HbA1c	0.721	<0.001	0.693	<0.001
TG	0.005	0.944	-0.04	0.601
TC	0.18	0.017	0.256	0.001
HDL-C	-0.218	0.004	-0.217	0.004
LDL-C	0.175	0.021	0.183	0.015
NLRP3	1	—	0.757	<0.001
Metrnl	0.757	<0.001	1	—
DKD	0.841	<0.001	0.784	<0.001

因变量	影响因素	β	SE	Wald χ²	P	95%CI
T2DM
	NLRP3	0.069	0.032	4.522	0.033	1.005~1.141
	Metrnl	0.02	0.004	23.342	<0.001	1.012~1.028
DKD
	NLRP3	0.337	0.066	25.686	<0.001	1.229~1.595
	Metrnl	0.021	0.004	22.942	<0.001	1.013~1.031

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