中性粒细胞和淋巴细胞比值预测2型糖尿病患者微量白蛋白尿的价值

doi:10.3969/j.issn.1004-583X.2022.09.008

摘要/Abstract

摘要：

目的探讨中性粒细胞和淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对2型糖尿病(type 2 diabetes mellitus, T2DM)患者微量白蛋白尿的预测价值。方法回顾性分析2020年11月至2021年6月河北省人民医院内分泌科收治的T2DM住院患者400例。根据24 h尿微量白蛋白检测结果分组,24 h尿微量白蛋白<30 mg为正常组(n=236), 30 mg≤24 h尿微量白蛋白<300 mg为微量白蛋白尿组(n=164),比较两组一般资料及实验室检查结果。采用二分类Logistic回归分析探究T2DM患者微量白蛋白尿的影响因素,通过绘制受试者工作特征(receiver operating characteristic, ROC)曲线,评估NLR及联合诊断对T2DM患者微量白蛋白尿的预测价值。结果微量白蛋白尿组年龄及高血压患者占比、白细胞(white blood cell, WBC)计数、中性粒细胞(absolute neutrophil, NEU)计数、NLR、甘油三酯(triacylglycerol, TG)、肌酐(creatinine, Scr)、尿素氮(urea nitrogen, BUN)高于正常组,估算的肾小球滤过率(estimated glomerular filtration rate, eGFR)和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)低于正常组, 差异有统计学意义(均P<0.05)。NLR单独预测T2DM患者微量白蛋白尿的ROC曲线下面积(area under the curve, AUC)为0.644[95%CI(0.586,0.701)],最佳截断值为2.81,灵敏度为46.1%,特异度为85.8%。NLR联合BUN、eGFR、TG、是否合并高血压的AUC为0.727[95%CI(0.678,0.777)],最佳截断值为0.426,灵敏度为59.9%,特异度为74.2%。结论 NLR可作为预测T2DM患者微量白蛋白尿的临床指标之一。

关键词: 糖尿病,2型, 白蛋白尿, 诊断, 预测, 中性粒细胞和淋巴细胞比值

Abstract:

Objective To determine the predictive value of neutrophil to lymphocyte ratio (NLR) for microalbuminuria of type 2 diabetes mellitus (T2DM). Methods A retrospective analysis was performed on 400 T2DM inpatients admitted to the Department of Endocrinology, Hebei General Hospital from November 2020 to June 2021. Using the results of 24 hour urinary microalbumin, the patients were assigned to the normal group (n=236, 24 hour urinary microalbumin<30 mg) and the microalbuminuria group (n=164, 30 mg≤24 hour urinary microalbumin<300 mg). The general data and laboratory results were compared between two groups, binary Logistic regression analysis was conducted to assess the influencing factors for microalbuminuria in T2DM patients. The predictive value of NLR and combined diagnosis on microalbuminuria in T2DM patients was evaluated by drawing receiver operating characteristic (ROC) curve. Results The percentage of patients with advanced age and hypertension, white blood cell (WBC) count, neutrophils absolute (NEU) count, NLR, triglyceride (TG), serum creatinine (Scr) and urea nitrogen (BUN) were higher in microalbuminuria group than the normal group, but the estimated glomerular filtration rate (eGFR) and high density lipoprotein cholesterol (HDL-C) were significantly lower than that in the normal group (all P<0.05). The area under the curve (AUC) of NLR alone for predicting microalbuminuria of T2DM patients was 0.644[95%CI(0.586, 0.701)], the best cutoff value for 2.81, the sensitivity for 46.1%, and the specificity for 85.8%. The AUC obtained by NLR combined with BUN, eGFR, TG, and whether hypertension was 0.727[95%CI (0.678, 0.777)], the optimal cutoff of 0.426, the sensitivity of 59.9%, and the specificity of 74.2%.Conclusion NLR can be used as one of the clinical indicators to predict microalbuminuria of T2DM patients.

Key words: diabetes mellitus, type 2, albuminuria, diagnosis, forecasting, neutrophil to lymphocyte ratio

中图分类号:

R587.1

王珍珍, 赵仕一, 冯鸶然, 马博清. 中性粒细胞和淋巴细胞比值预测2型糖尿病患者微量白蛋白尿的价值[J]. 临床荟萃, 2022, 37(9): 808-812.

Wang Zhenzhen, Zhao shiyi, Feng Siran, Ma Boqing. Predictive value of neutrophil to lymphocyte ratio for microalbuminuria of patients with type 2 diabetes mellitus[J]. Clinical Focus, 2022, 37(9): 808-812.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.09.008

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I9/808

图/表 4

参考文献 21

[1]	Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition[J]. Diabetes Res Clin Pract, 2019, 157:107843. doi: 10.1016/j.diabres.2019.107843 URL
[2]	Karakaya S, Altay M, Kaplan Efe F, et al. The neutrophil-lymphocyte ratio and its relationship with insulin resistance in obesity[J]. Turk J Med Sci, 2019, 49(1): 245-248. doi: 10.3906/sag-1804-68 pmid: 30761879
[3]	Zhang L, Long J, Jiang W, et al. Trends in chronic kidney disease in China[J]. N Engl J Med, 2016, 375(9): 905-906. doi: 10.1056/NEJMc1602469 URL
[4]	Jaaban M, Zetoune AB, Hesenow S, et al. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as novel risk markers for diabetic nephropathy in patients with type 2 diabetes[J]. Heliyon, 2021, 7(7):e07564. doi: 10.1016/j.heliyon.2021.e07564 URL
[5]	Tesch GH. Diabetic nephropathy-is this an immune disorder?[J]. Clin Sci (Lond), 2017, 131(16): 2183-2199. doi: 10.1042/CS20160636 pmid: 28760771
[6]	Wan H, Wang Y, Fang S, et al. Associations between the neutrophil-to-lymphocyte ratio and diabetic complications in adults with diabetes: A cross-sectional study[J]. J Diabetes Res, 2020, 2020:6219545.
[7]	Uwaezuoke SN. The role of novel biomarkers in predicting diabetic nephropathy: A review[J]. Int J Nephrol Renovasc Dis, 2017, 10:221-231. doi: 10.2147/IJNRD.S143186 pmid: 28860837
[8]	Chen X, Ma J, Kwan T, et al. Blockade of HMGB1 attenuates diabetic nephropathy in mice[J]. Sci Rep, 2018, 8(1):8319. doi: 10.1038/s41598-018-26637-5 pmid: 29844451
[9]	Winter L, Wong LA, Jerums G, et al. Use of readily accessible inflammatory markers to predict diabetic kidney disease[J]. Front Endocrinol (Lausanne), 2018, 9:225. doi: 10.3389/fendo.2018.00225 URL
[10]	StojkovicLalosevic M, Pavlovic Markovic A, Stankovic S, et al. Combined diagnostic efficacy of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) as biomarkers of systemic inflammation in the diagnosis of colorectal cancer[J]. Dis Markers, 2019, 2019:6036979.
[11]	Li H, Lu X, Xiong R, et al. High Neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients[J]. Mediators Inflamm, 2017, 2017:9327136.
[12]	Zhang Y, Lu JJ, Du YP, et al. Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in gastric cancer[J]. Medicine (Baltimore), 2018, 97(12):e0144. doi: 10.1097/MD.0000000000010144 URL
[13]	Wang Y, Sun K, Shen J, et al. Novel prognostic nomograms based on inflammation-related markers for patients with hepatocellular carcinoma underwent hepatectomy[J]. Cancer Res Treat, 2019, 51(4):1464-1478. doi: 10.4143/crt.2018.657 pmid: 30913869
[14]	姚青林, 王景杰, 李欢, 等. 中性粒细胞/淋巴细胞比率、C反应蛋白/白蛋白比率、血小板/淋巴细胞比率与结直肠癌患者预后的关系[J]. 疑难病杂志, 2020, 19(6):595-598+616.
[15]	Liu J, Liu X, Li Y, et al. The association of neutrophil to lymphocyte ratio, mean platelet volume, and platelet distribution width with diabetic retinopathy and nephropathy: A meta-analysis[J]. Biosci Rep, 2018, 38(3):BSR20180172.
[16]	Kahraman C, Kahraman NK, Aras B, et al. The relationship between neutrophil-to-lymphocyte ratio and albuminuria in type 2 diabetic patients: A pilot study[J]. Arch Med Sci, 2016, 12(3):571-575. doi: 10.5114/aoms.2016.59931 pmid: 27279850
[17]	Kutlugun AA, Ebinc FA, Ozturk MT, et al. Association of neutrophil-to-lymphocyte ratio and microalbuminuria in patients with normal eGFR[J]. Rom J Intern Med, 2018, 56(1):21-26. doi: 10.1515/rjim-2017-0036 pmid: 28945608
[18]	Wang JR, Chen Z, Yang K, et al. Association between neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and diabetic retinopathy among diabetic patients without a related family history[J]. DiabetolMetab Syndr, 2020, 12:55.
[19]	Khandare SA, Chittawar S, Nahar N, et al. Study of neutrophil-lymphocyte ratio as novel marker for diabetic nephropathy in type 2 diabetes[J]. Indian J Endocrinol Metab, 2017, 21(3): 387-92. doi: 10.4103/ijem.IJEM_476_16 pmid: 28553592
[20]	Zhou Y, Yuan J, Qi C, et al. Calcium dobesilate may alleviate diabetes-induced endothelial dysfunction and inflammation[J]. Mol Med Rep, 2017, 16(6):8635-8642. doi: 10.3892/mmr.2017.7740 URL
[21]	Warren AM, Knudsen ST, Cooper ME. Diabetic nephropathy: An insight into molecular mechanisms and emerging therapies[J]. Expert OpinTher Targets, 2019, 23(7):579-591.

组别	例数	性别[例(%)]		年龄 (岁)	BMI (kg/m²)	糖尿病病程 (年)	高血压病史[例(%)]
组别	例数	男	女	年龄 (岁)	BMI (kg/m²)	糖尿病病程 (年)	有	无
正常组	236	134(56.8)	102(43.2)	57.36±12.14	25.39(23.46,27.73)	10(3, 15)	111(47.0)	125(53.0)
微量白蛋白尿组	164	93(56.7)	71(43.3)	60.87±13.95	25.64(23.39,28.34)	9(4, 16)	110(67.1)	54(32.9)
统计值		χ²=0.000		t=-2.613	Z=-0.620	Z=-1.228	χ²=15.716
P值		0.989		0.009	0.535	0.219	0.000

组别	例数	性别[例(%)]		年龄 (岁)	BMI (kg/m²)	糖尿病病程 (年)	高血压病史[例(%)]
组别	例数	男	女	年龄 (岁)	BMI (kg/m²)	糖尿病病程 (年)	有	无
正常组	236	134(56.8)	102(43.2)	57.36±12.14	25.39(23.46,27.73)	10(3, 15)	111(47.0)	125(53.0)
微量白蛋白尿组	164	93(56.7)	71(43.3)	60.87±13.95	25.64(23.39,28.34)	9(4, 16)	110(67.1)	54(32.9)
统计值		χ²=0.000		t=-2.613	Z=-0.620	Z=-1.228	χ²=15.716
P值		0.989		0.009	0.535	0.219	0.000

组别	例数	WBC计数 (×10⁹/L)	NEU计数 (×10⁹/L)	LYM计数 (×10⁹/L)	HbA₁c (%)	FPG (mmol/L)	TC (mmol/L)	TG (mmol/L)
正常组	236	5.76 (5.07, 7.10)	3.50 (2.92, 4.39)	1.76 (1.42, 2.10)	8.60 (6.93, 10.10)	8.06 (6.19, 11.52)	4.45 (3.67, 5.10)	1.23 (0.93, 2.14)
微量白蛋白尿组	164	6.67 (5.71, 7.77)	4.17 (3.20, 5.06)	1.76 (1.43, 2.22)	8.50 (7.00, 10.60)	7.70 (6.34, 11.85)	4.33 (3.57, 5.29)	1.57 (1.08, 2.38)
Z值		-4.297	-3.921	-0.663	-1.000	-0.158	-0.321	-2.516
P值		0.000	0.000	0.507	0.318	0.875	0.749	0.012
组别	例数	HDL-C (mmol/L)	LDL-C (mmol/L)	BUN (mmol/L)	Scr (μmol/L)	eGFR [ml/(min·1.73 m²)]	UA (μmol/L)	NLR
正常组	236	1.04 (0.85, 1.22)	2.89 (2.33, 3.44)	4.80 (4.20, 5.60)	70.00 (62.93, 77.65)	96.66 (83.19, 103.43)	284.30 (237.70, 366.40)	1.98 (1.65, 2.69)
微量白蛋白尿组	164	0.96 (0.83, 1.12)	2.81 (2.26, 3.53)	5.40 (4.50, 6.70)	74.80 (63.90, 85.10)	86.54 (70.42, 99.65)	292.00 (245.80, 354.90)	2.30 (1.57, 3.53)
Z值		-2.445	-0.516	-4.297	-3.424	-4.404	-0.191	-2.089
P值		0.014	0.606	0.000	0.001	0.000	0.848	0.037

组别	例数	WBC计数 (×10⁹/L)	NEU计数 (×10⁹/L)	LYM计数 (×10⁹/L)	HbA₁c (%)	FPG (mmol/L)	TC (mmol/L)	TG (mmol/L)
正常组	236	5.76 (5.07, 7.10)	3.50 (2.92, 4.39)	1.76 (1.42, 2.10)	8.60 (6.93, 10.10)	8.06 (6.19, 11.52)	4.45 (3.67, 5.10)	1.23 (0.93, 2.14)
微量白蛋白尿组	164	6.67 (5.71, 7.77)	4.17 (3.20, 5.06)	1.76 (1.43, 2.22)	8.50 (7.00, 10.60)	7.70 (6.34, 11.85)	4.33 (3.57, 5.29)	1.57 (1.08, 2.38)
Z值		-4.297	-3.921	-0.663	-1.000	-0.158	-0.321	-2.516
P值		0.000	0.000	0.507	0.318	0.875	0.749	0.012
组别	例数	HDL-C (mmol/L)	LDL-C (mmol/L)	BUN (mmol/L)	Scr (μmol/L)	eGFR [ml/(min·1.73 m²)]	UA (μmol/L)	NLR
正常组	236	1.04 (0.85, 1.22)	2.89 (2.33, 3.44)	4.80 (4.20, 5.60)	70.00 (62.93, 77.65)	96.66 (83.19, 103.43)	284.30 (237.70, 366.40)	1.98 (1.65, 2.69)
微量白蛋白尿组	164	0.96 (0.83, 1.12)	2.81 (2.26, 3.53)	5.40 (4.50, 6.70)	74.80 (63.90, 85.10)	86.54 (70.42, 99.65)	292.00 (245.80, 354.90)	2.30 (1.57, 3.53)
Z值		-2.445	-0.516	-4.297	-3.424	-4.404	-0.191	-2.089
P值		0.014	0.606	0.000	0.001	0.000	0.848	0.037

变量	回归系数	标准误	Wald χ²值	P值	OR值	95%CI
变量	回归系数	标准误	Wald χ²值	P值	OR值	下限	上限
高血压	0.732	0.234	9.755	0.002	2.078	1.304	3.289
BUN	0.321	0.089	13.020	0.000	1.379	1.158	1.641
eGFR	-0.032	0.013	5.905	0.015	0.969	0.944	0.994
TG	0.116	0.053	4.761	0.029	1.123	1.012	1.247
NLR	0.206	0.094	4.788	0.029	1.228	1.022	1.477
常量	3.426	2.547	1.810	0.179	30.742