Serum expression of SMAD2 and SOX6 in patients with type 2 diabetes mellitus and their relationship with proteinuria

doi:10.3877/cma.j.issn.2095-3216.2024.03.004

Abstract

Abstract:

Objective

To investigate the relationship of serum expression of SMAD2 and SOX6 with proteinuria in patients with type 2 diabetes mellitus (T2DM).

Methods

Clinical data of T2DM patients admitted to our hospital from March 2022 to April 2023 were analyzed retrospectively. According to urinary albumin/creatinine ratio (UACR), the patients were divided into three groups: normal albuminuria group (NA group, UACR <30 mg/g), microalbuminuria group (MA group, UACR 30-299 mg/g), and large albuminuria group (LA group, UACR≥300 mg/g). General information, serum expression of SMAD2 and SOX6, and other laboratory indicators were collected. Pearson correlation method was applied to analyze the correlation of serum SMAD2 and SOX6 levels with UACR and estimated glomerular filtration rate (eGFR) in the T2DM patients. The receiver operating characteristic (ROC) curve method was used to analyze the roles of serum SMAD2 and SOX in the diagnosis of macroproteinuria. The influencing factors of proteinuria were analyzed by logistic regression method.

Results

A total of 164 patients with T2DM were enrolled, including 70 in the NA group, 43 in the MA group, and 51 in the LA group. Serum levels of SMAD2 and SOX6 in the NA, MA and LA groups gradually increased (F=81.645, 45.069, all P<0.05). Multifactor logistic regression analysis showed that high levels of SMAD2 (OR=2.015, 95%CI: 1.244-3.263), SOX6 (OR=2.467, 95%CI: 1.476-4.122), UACR (OR=2.840, 95%CI: 1.605-5.023), and eGFR (OR=0.799, 95%CI: 0.680-0.938) were influencing factors of proteinuria (P<0.05). Correlation analysis showed that SMAD2 (r=0.559, P<0.001) and SOX6 (r=0.628, P<0.001) were positively correlated with UACR, while SMAD2 (r=-0.550, P<0.001) and SOX6 (r=-0.474, P<0.001) were negatively correlated with eGFR. ROC curve analysis showed that the areas under the curve (AUC) of serum SMAD2 and SOX6 for diagnosing large albuminuria were 0.844 and 0.765, and the cut-off values were 11.71 μg/L and 3.67 ng/L, respectivey. The AUC of combined SMAD2 and SOX6 for detection was 0.912, being better than that of SMAD2 (Z/P=2.995/0.002) or SOX6 (Z/P=3.861/<0.001) alone.

Conclusion

Serum levels of SMAD2 and SOX6 in T2DM patients were correlated with proteinuria, whose significance needs further study.

Key words: Type 2 diabetes mellitus, SMAD2, SOX6, Urinary albumin/creatinine ratio, Diabetic kidney disease

Wenqi Lu, Yanru Zhao, Huandi Li, Xinna Fan, Jia Wang, Ping Li. Serum expression of SMAD2 and SOX6 in patients with type 2 diabetes mellitus and their relationship with proteinuria[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2024, 13(03): 145-151.

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References 21

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项目	NA组(70例)	MA组(43例)	LA组(51例)	F/χ²值	P值
年龄(岁)	54.05±7.69	53.94±8.01	54.33±7.58	0.033	0.968
男/女	36/34	25/18	27/24	0.498	0.780
BMI(kg/m²)	24.46±1.94	24.73±2.52	24.29±2.16	0.483	0.618
吸烟	21	14	16	0.084	0.959
高血压	19	16	15	1.314	0.518
高血脂症	9	7	8	0.315	0.854
T2DM家族史	28	17	19	0.100	0.951
降糖治疗
口服降糖药	22	13	16	0.656	0.957
胰岛素皮下注射	26	17	22
联合用药	22	13	13
T2DM病程(年)	5.92±1.40	8.89±2.35^a	12.31±3.28^ab	107.363	<0.001
SBP(mmHg)	121.79±8.95	130.14±9.5^a	135.67±10.35^ab	32.271	<0.001
DBP(mmHg)	77.64±7.06	79.26±8.34	77.72±7.91	0.679	0.509
DAO(U/L)	3.48±1.02	5.77±1.26^a	7.09±1.53^ab	127.041	<0.001
ET(EU/ml)	0.27±0.05	0.36±0.07^a	0.41±0.05^ab	97.967	<0.001
D-Lac(mmol/L)	4.61±0.56	5.72±0.67^a	6.50±0.59^ab	150.868	<0.001
FPG(mmol/L)	8.69±1.35	9.08±1.90	9.55±3.02	2.398	0.094
TC(mmol/L)	4.53±1.54	4.99±1.65	4.91±1.73	1.339	0.265
TG(mmol/L)	1.73±0.41	1.80±0.49	1.76±0.55	0.286	0.751
Scr(μmol/L)	83.07±14.63	85.49±11.08	185.62±17.20^ab	841.947	<0.001
BUN(mmol/L)	5.69±1.42	6.34±1.15	35.27±6.31^ab	1114.082	<0.001
HbA1c(%)	8.54±1.65	9.02±1.47	9.70±2.16^a	6.243	0.002
FINS(mU/L)	10.53±1.77	11.46±2.15	12.19±2.55^a	9.083	<0.001
HOMA-IR	3.47±1.24	4.19±1.38^a	4.55±1.49^a	9.928	<0.001
UACR(mg/g)	16.09±3.50	98.76±17.49^a	367.18±39.40^ab	3325.513	<0.001
eGFR[ml/(min·1.73 m²]	94.36±14.14	80.58±13.07	69.47±6.52^ab	64.904	<0.001

项目	NA组(70例)	MA组(43例)	LA组(51例)	F/χ²值	P值
年龄(岁)	54.05±7.69	53.94±8.01	54.33±7.58	0.033	0.968
男/女	36/34	25/18	27/24	0.498	0.780
BMI(kg/m²)	24.46±1.94	24.73±2.52	24.29±2.16	0.483	0.618
吸烟	21	14	16	0.084	0.959
高血压	19	16	15	1.314	0.518
高血脂症	9	7	8	0.315	0.854
T2DM家族史	28	17	19	0.100	0.951
降糖治疗
口服降糖药	22	13	16	0.656	0.957
胰岛素皮下注射	26	17	22
联合用药	22	13	13
T2DM病程(年)	5.92±1.40	8.89±2.35^a	12.31±3.28^ab	107.363	<0.001
SBP(mmHg)	121.79±8.95	130.14±9.5^a	135.67±10.35^ab	32.271	<0.001
DBP(mmHg)	77.64±7.06	79.26±8.34	77.72±7.91	0.679	0.509
DAO(U/L)	3.48±1.02	5.77±1.26^a	7.09±1.53^ab	127.041	<0.001
ET(EU/ml)	0.27±0.05	0.36±0.07^a	0.41±0.05^ab	97.967	<0.001
D-Lac(mmol/L)	4.61±0.56	5.72±0.67^a	6.50±0.59^ab	150.868	<0.001
FPG(mmol/L)	8.69±1.35	9.08±1.90	9.55±3.02	2.398	0.094
TC(mmol/L)	4.53±1.54	4.99±1.65	4.91±1.73	1.339	0.265
TG(mmol/L)	1.73±0.41	1.80±0.49	1.76±0.55	0.286	0.751
Scr(μmol/L)	83.07±14.63	85.49±11.08	185.62±17.20^ab	841.947	<0.001
BUN(mmol/L)	5.69±1.42	6.34±1.15	35.27±6.31^ab	1114.082	<0.001
HbA1c(%)	8.54±1.65	9.02±1.47	9.70±2.16^a	6.243	0.002
FINS(mU/L)	10.53±1.77	11.46±2.15	12.19±2.55^a	9.083	<0.001
HOMA-IR	3.47±1.24	4.19±1.38^a	4.55±1.49^a	9.928	<0.001
UACR(mg/g)	16.09±3.50	98.76±17.49^a	367.18±39.40^ab	3325.513	<0.001
eGFR[ml/(min·1.73 m²]	94.36±14.14	80.58±13.07	69.47±6.52^ab	64.904	<0.001

指标	NA组(70例)	MA组(43例)	LA组(51例)	F值	P值
SMAD2(μg/L)	9.13±1.57	11.05±1.82^a	13.79±2.54^ab	81.645	<0.001
SOX6(ng/L)	2.69±0.55	3.12±0.75^a	3.88±0.78^ab	45.069	<0.001

指标	NA组(70例)	MA组(43例)	LA组(51例)	F值	P值
SMAD2(μg/L)	9.13±1.57	11.05±1.82^a	13.79±2.54^ab	81.645	<0.001
SOX6(ng/L)	2.69±0.55	3.12±0.75^a	3.88±0.78^ab	45.069	<0.001

项目	B值	标准误	Wald	P值	OR值	95%CI
T2DM病程	0.400	0.217	3.411	0.065	1.493	0.975～2.284
SBP	0.420	0.274	2.349	0.125	1.522	0.889～2.604
DAO	0.017	0.255	0.005	0.944	1.018	0.617～1.678
ET	0.614	0.341	3.248	0.071	1.849	0.947～3.607
D-Lac	0.265	0.179	2.198	0.138	1.304	0.918～1.852
HbA1c	0.063	0.162	0.155	0.693	1.066	0.775～1.464
BUN	0.712	0.365	3.810	0.051	2.039	0.997～4.169
Scr	1.084	0.284	14.572	<0.001	2.957	1.694～5.159
FINS	0.825	0.426	3.755	0.053	2.283	0.991～5.261
HOMA-IR	0.894	0.458	3.814	0.051	2.446	0.996～6.002
UACR	1.168	0.342	11.561	0.001	3.199	1.636～6.253
eGFR	－0.207	0.076	7.421	0.006	0.813	0.700～0.943
SMAD2	1.059	0.291	13.248	<0.001	2.884	1.630～5.101
SOX6	0.941	0.275	11.705	0.001	2.562	1.494～4.392

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