唾液血液尿酸比与糖尿病周围神经病变的相关性

doi:10.3969/j.issn.1004-583X.2023.01.003

摘要/Abstract

摘要：

目的探讨2型糖尿病(T2DM)中伴有糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)患者血液尿酸(blood uric acid, BUA)和唾液尿酸(salivary uric acid, SUA)的动态变化, 并分析SUA/BUA与DPN的相关性及其预测价值。方法选取2021年1月至2022年12月在我院内分泌科确诊的164例T2DM患者的临床资料, 根据临床症状及肌电图等辅助检查结果将所有患者分为DPN组( $n$ =103)和单纯T2DM组( $n$ =61)。检测并比较两组一般资料、SUA以及SUA/BUA情况;多因素Logistic回归分析DPN的相关影响因素;利用受试者工作特征(receiver operator characteristic curve,ROC)曲线评估相关影响因素的预测价值。结果 Logistic回归分析结果表明, 糖化血红蛋白( glycosylated hemoglobin,HbA₁c)、SUA、SUA/BUA为DPN发生的危险因素。ROC曲线分析表明: HbA₁c的AUC为0.637, 敏感度为50.8%, 特异度为78.6%, 最佳切点值为8.15。SUA的AUC为0.698, 敏感度为52.4%, 特异度为83.6%, 最佳切点值为388.43。BUA的AUC为0.762, 敏感度为86.4%, 特异度为73.8%, 最佳切点值为1.01。结论 SUA/BUA与DPN发病密切相关, 对诊断DPN有一定预测价值。

关键词: 糖尿病神经病变, 尿酸, 唾液, 血液

Abstract:

Objective To explore the dynamic change of blood uric acid (BUA) and salivary uric acid (SUA) in type 2 diabetes mellitus (T2DM) patients with diabetic peripheral neuropathy (DPN), and to study the correlation between ratio of SUA to BUA (SUA/BUA) and DPN, and its predictive value. Methods The clinic data of 164 T2DM patients in the Department of Endocrinology of our hospital from January 2021 to December 2022 was analyzed, and the patients were assigned to the DPN group ( $n$ =103) and the simple T2DM group ( $n$ =61) based on the clinical symptoms and electromyography results. The general data, SUA and SUA/BUA were compared. The DPN-related factors and their predictive value were respectively assessed by the multiple Logistic regression and receiver operator characteristic (ROC) curve. Results Logistic regression analysis showed that the risk factors of DPN were glycosylated hemoglobin (HbA₁c), SUA, and SUA/BUA. ROC curve analysis showed that areas under curve (AUC), sensitivity, specificity, and optimal cut-off point of HbA₁c were 0.637, 50.8%, 78.6%, and 8.15, respectively, those of SUA were 0.698, 52.4%, 83.6%, 388.43, respectively, and those of BUA were 0.762, 86.4%, 73.8%, 1.01, respectively. Conclusion SUA/BUA is closely associated with DPN, and with a certain predictive value in diagnosis of DPN.

Key words: diabetic neuropathies, uric acid, saliva, blood

中图分类号:

R587.25

鞠岩, 郭鹏, 吴伯韬, 刘新宇. 唾液血液尿酸比与糖尿病周围神经病变的相关性[J]. 临床荟萃, 2023, 38(1): 37-41.

Ju Yan, Guo Peng, Wu Botao, Liu Xinyu. Correlation between ratio of salivary uric acid to blood uric acid and diabetic peripheral neuropathy[J]. Clinical Focus, 2023, 38(1): 37-41.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.01.003

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I1/37

图/表 4

表1 一般资料比较

Tab.1 Comparison of general data

组别	T2DM ( $n$ =61)	DPN ( $n$ =103)	统计值	$P$ 值
年龄(岁)	58.61±5.78	57.8±6.01	0.77	0.445
性别(男)[例(%)]	34(55.7)	40(38.9)	3.16	0.083
BMI(kg/m²)[例(%)]
≤24	25(41.0)	30(29.1)
>24~28	31(50.8)	54(52.4)	4.38	0.114
>28	5(8.2)	19(18.5)
DM病程(年)[例(%)]
≤5	20(32.8)	34(33.0)
5~10	30(49.2)	46(44.7)	0.51	0.781
>10	11(18.0)	23(22.3)
高血压病史[例(%)]	22(36.1)	33(32.0)	0.28	0.601
FPG(mmol/L)	9.83±3.60	10.14±3.61	-0.54	0.592
HbA₁c(%)	8.55±2.64	9.50±2.02	-2.59	0.010
TC(mmol/L)	4.76±1.17	4.82±1.35	-0.29	0.774
TG(mmol/L)	1.98±1.80	2.63±1.91	-2.18	0.031
HDL-C(mmol/L)	1.22±0.53	1.14±0.50	0.89	0.385
LDL-C(mmol/L)	2.42±0.63	2.52±0.81	-0.79	0.433
BUN(mmol/L)	5.82±1.84	6.37±2.17	-1.67	0.104
Scr(μmol/L)	58.46±19.10	63.71±18.73	-1.72	0.090
BUA(μmol/L)	358.16±143.17	324.65±173.53	1.27	0.215
SUA(μmol/L)	328.07±76.16	393.76±104.83	-4.27	0.001
SUA/BUA	1.02±0.41	1.43±0.55	-5.30	0.001

表1 一般资料比较

Tab.1 Comparison of general data

组别	T2DM ( $n$ =61)	DPN ( $n$ =103)	统计值	$P$ 值
年龄(岁)	58.61±5.78	57.8±6.01	0.77	0.445
性别(男)[例(%)]	34(55.7)	40(38.9)	3.16	0.083
BMI(kg/m²)[例(%)]
≤24	25(41.0)	30(29.1)
>24~28	31(50.8)	54(52.4)	4.38	0.114
>28	5(8.2)	19(18.5)
DM病程(年)[例(%)]
≤5	20(32.8)	34(33.0)
5~10	30(49.2)	46(44.7)	0.51	0.781
>10	11(18.0)	23(22.3)
高血压病史[例(%)]	22(36.1)	33(32.0)	0.28	0.601
FPG(mmol/L)	9.83±3.60	10.14±3.61	-0.54	0.592
HbA₁c(%)	8.55±2.64	9.50±2.02	-2.59	0.010
TC(mmol/L)	4.76±1.17	4.82±1.35	-0.29	0.774
TG(mmol/L)	1.98±1.80	2.63±1.91	-2.18	0.031
HDL-C(mmol/L)	1.22±0.53	1.14±0.50	0.89	0.385
LDL-C(mmol/L)	2.42±0.63	2.52±0.81	-0.79	0.433
BUN(mmol/L)	5.82±1.84	6.37±2.17	-1.67	0.104
Scr(μmol/L)	58.46±19.10	63.71±18.73	-1.72	0.090
BUA(μmol/L)	358.16±143.17	324.65±173.53	1.27	0.215
SUA(μmol/L)	328.07±76.16	393.76±104.83	-4.27	0.001
SUA/BUA	1.02±0.41	1.43±0.55	-5.30	0.001

表2 DPN危险因素的Logistic 回归分析

Tab.2 Logistic regression analysis for DPN-related risk factors

自变量	$B$	$S E$	Wald χ²值	$P$ 值	$O R$ 值	95% $C I$
HbA₁c	0.18	0.09	4.21	0.040	1.19	1.008~1.410
TG	0.17	0.11	2.35	0.131	1.19	0.953~1.484
SUA	0.01	0.02	10.95	0.001	1.01	1.003~1.013
SUA/BUA	1.90	0.47	16.71	0.001	6.67	2.691~16.674

表2 DPN危险因素的Logistic 回归分析

Tab.2 Logistic regression analysis for DPN-related risk factors

自变量	$B$	$S E$	Wald χ²值	$P$ 值	$O R$ 值	95% $C I$
HbA₁c	0.18	0.09	4.21	0.040	1.19	1.008~1.410
TG	0.17	0.11	2.35	0.131	1.19	0.953~1.484
SUA	0.01	0.02	10.95	0.001	1.01	1.003~1.013
SUA/BUA	1.90	0.47	16.71	0.001	6.67	2.691~16.674

表3 HbA1c、SUA、SUA/BUA对DPN的诊断效能比较

Tab.3 Comparison of the diagnostic efficacy of HbA1c, SUA, SUA/BUA for DPN

变量	AUC	SE	敏感度	特异度	切点	$P$ 值	95% $C I$
HbA₁c	0.637	0.047	0.508	0.786	8.15	0.003	0.545~0.729
SUA	0.698	0.041	0.524	0.836	388.43	0.001	0.617~0.779
SUA/BUA	0.762	0.042	0.864	0.738	1.01	0.001	0.680~0.843

表3 HbA1c、SUA、SUA/BUA对DPN的诊断效能比较

Tab.3 Comparison of the diagnostic efficacy of HbA1c, SUA, SUA/BUA for DPN

变量	AUC	SE	敏感度	特异度	切点	$P$ 值	95% $C I$
HbA₁c	0.637	0.047	0.508	0.786	8.15	0.003	0.545~0.729
SUA	0.698	0.041	0.524	0.836	388.43	0.001	0.617~0.779
SUA/BUA	0.762	0.042	0.864	0.738	1.01	0.001	0.680~0.843

图1 HbA1c、SUA、SUA/BUA对DPN的预测价值

Fig.1 Predictive value of HbA1c, SUA, SUA/BUA for DPN

参考文献 33

[1]	Hicks CW, Selvin E. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes[J]. Curr Diab Rep, 2019, 19(10):86. doi: 10.1007/s11892-019-1212-8 URL
[2]	Liu X, Xu Y, An M, et al. The risk factors for diabetic peripheral neuropathy: A meta-analysis[J]. PLoS One, 2019, 14(2):e0212574. doi: 10.1371/journal.pone.0212574 URL
[3]	Armstrong DG, Boulton A, Bus SA. Diabetic foot ulcers and their recurrence[J]. N Engl J Med, 2017, 376(24): 2367-2375. doi: 10.1056/NEJMra1615439 URL
[4]	Zhang P, Lu J, Jing Y, et al. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis[J]. Ann Med, 2017, 49(2): 106-116. doi: 10.1080/07853890.2016.1231932 URL
[5]	Selvarajah D, Kar D, Khunti K, et al. Diabetic peripheral neuropathy: Advances in diagnosis and strategies for screening and early intervention[J]. Lancet Diabetes Endocrinol, 2019, 7(12): 938-948. doi: 10.1016/S2213-8587(19)30081-6 URL
[6]	Yu S, Chen Y, Hou X, et al. Serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes: A systematic review and meta-analysis[J]. Mol Neurobiol, 2016, 53(2):1045-1051. doi: 10.1007/s12035-014-9075-0 pmid: 25579387
[7]	Carmichael J, Fadavi H, Ishibashi F, et al. Advances in screening, early diagnosis and accurate staging of diabetic neuropathy[J]. Front Endocrinol (Lausanne), 2021, 12:671257. doi: 10.3389/fendo.2021.671257 URL
[8]	Corey-Bloom J, Haque A, Aboufadel S, et al. Uric acid as a potential peripheral biomarker for disease features in Huntington's patients[J]. Front Neurosci, 2020, 14:73. doi: 10.3389/fnins.2020.00073 URL
[9]	Vernerová A, Kujovská Krčmová L, Melichar B, et al. Non-invasive determination of uric acid in human saliva in the diagnosis of serious disorders[J]. Clin Chem Lab Med, 2021, 59(5):797-812. doi: 10.1515/cclm-2020-1533 pmid: 33554551
[10]	Araujo DS, Scudine K, Pedroni-Pereira A, et al. Salivary uric acid is a predictive marker of body fat percentage in adolescents[J]. Nutr Res, 2020, 74:62-70. doi: S0271-5317(19)30730-4 pmid: 31954275
[11]	Kaewput W, Thongprayoon C, Rangsin R, et al. The association between serum uric acid and peripheral neuropathy in patients with type 2 diabetes mellitus: A multicenter nationwide crosssectional study[J]. Korean J Fam Med, 2020, 41(3):189-194. doi: 10.4082/kjfm.18.0205 pmid: 32456387
[12]	Maciejczyk M, Pawlukianiec C, Żendzian-Piotrowska M, et al. Salivary redox biomarkers in insulin resistance: Preclinical studies in an animal model[J]. Oxid Med Cell Longev, 2021, 2021: 3734252.
[13]	中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021, 13(4): 315-409.
[14]	中华医学会糖尿病学分会神经并发症学组. 糖尿病神经病变诊治专家共识(2021年版)[J]. 中华内分泌代谢杂志, 2021, 37(6): 499-515.
[15]	Klimiuk A, Zalewska A, Sawicki R, et al. Salivary oxidative stress increases with the progression of chronic heart failure[J]. J Clin Med, 2020, 9(3):769. doi: 10.3390/jcm9030769 URL
[16]	Maciejczyk M, Taranta-Janusz K, Wasilewska A, et al. A case-control study of salivary redox homeostasis in hypertensive children. Can salivary uric acid be a marker of hypertension?[J]. J Clin Med, 2020, 9(3):837. doi: 10.3390/jcm9030837 URL
[17]	Maciejczyk M, Bielas M, Zalewska A, et al. Salivary biomarkers of oxidative stress and inflammation in stroke patients: From basic research to clinical practice[J]. Oxid Med Cell Longev, 2021, 2021: 5545330.
[18]	Feldman EL, Nave KA, Jensen TS, et al. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain[J]. Neuron, 2017, 93(6):1296-1313. doi: S0896-6273(17)30089-2 pmid: 28334605
[19]	Baum P, Toyka KV, Blüher M, et al. Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN)-new aspects[J]. Int J Mol Sci, 2021, 22(19):10835. doi: 10.3390/ijms221910835 URL
[20]	Lupachyk S, Watcho P, Hasanova N, et al. Triglyceride, nonesterified fatty acids, and prediabetic neuropathy: Role for oxidative-nitrosative stress[J]. Free Radic Biol Med, 2012, 52(8):1255-1263. doi: 10.1016/j.freeradbiomed.2012.01.029 URL
[21]	Xu T, Weng Z, Pei C, et al. The relationship between neutrophil-to-lymphocyte ratio and diabetic peripheral neuropathy in type 2 diabetes mellitus[J]. Medicine (Baltimore), 2017, 96(45):e8289. doi: 10.1097/MD.0000000000008289 URL
[22]	Soukup M, Biesiada I, Henderson A, et al. Salivary uric acid as a noninvasive biomarker of metabolic syndrome[J]. Diabetol Metab Syndr, 2012, 4(1):14. doi: 10.1186/1758-5996-4-14 pmid: 22515434
[23]	Maciejczyk M, Gerreth P, Zalewska A, et al. Salivary gland dysfunction in stroke patients is associated with increased protein glycoxidation and nitrosative stress[J]. Oxid Med Cell Longev, 2020, 2020:6619439.
[24]	Younus H, Ahmad S, Alam MF. Correlation between the activity of aldehyde dehydrogenase and oxidative stress markers in the saliva of diabetic patients[J]. Protein Pept Lett, 2020, 27(1):67-73. doi: 10.2174/0929866526666191002115121 URL
[25]	Stavniichuk R, Shevalye H, Lupachyk S, et al. Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy[J]. Diabetes Metab Res Rev, 2014, 30(8):669-678. doi: 10.1002/dmrr.2549 URL
[26]	Sifuentes-Franco S, Pacheco-Moisés FP, Rodríguez-Carrizalez AD, et al. The role of oxidative stress, mitochondrial function, and autophagy in diabetic polyneuropathy[J]. J Diabetes Res, 2017, 2017: 1673081.
[27]	Al-Rawi NH. Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics[J]. Diab Vasc Dis Res, 2011, 8(1):22-28. doi: 10.1177/1479164110390243 URL
[28]	Żukowski P, Maciejczyk M, Waszkiel D. Sources of free radicals and oxidative stress in the oral cavity[J]. Arch Oral Biol,2018, 92: 8-17.
[29]	Maciejczyk M, Zalewska A, Gerreth AK. Salivary redox biomarkers in selected neurodegenerative diseases[J]. J Clin Med, 2020, 9(2):497. doi: 10.3390/jcm9020497 URL
[30]	Zalewska A, Klimiuk A, Zięba S, et al. Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer's disease[J]. Sci Rep, 2021, 11(1):23904. doi: 10.1038/s41598-021-03456-9 pmid: 34903846
[31]	Fathi S, Borzouei S, Goodarzi MT, et al. Evaluation of salivary antioxidants and oxidative stress markers in type 2 diabetes mellitus: A retrospective cohort study[J]. Endocr Metab Immune Disord Drug Targets, 2020, 20(4): 584-590. doi: 10.2174/1871530319666191016103222 pmid: 31622212
[32]	Casadei G, Filippini M, Brognara L. Glycated hemoglobin (HbA₁c) as a biomarker for diabetic foot peripheral neuropathy[J]. Diseases, 2021, 9(1):16. doi: 10.3390/diseases9010016 URL
[33]	Su JB, Zhao LH, Zhang XL, et al. HbA₁c variability and diabetic peripheral neuropathy in type 2 diabetic patients[J]. Cardiovasc Diabetol, 2018, 17(1):47. doi: 10.1186/s12933-018-0693-0 URL