2型糖尿病合并肺结核感染患者初诊临床特征分析.pdf

riticalISAr论776Clin J Med Offic,Aug,2023V临床军医杂志2023年8 月第51卷第8 期2型糖尿病合并肺结核感染患者初诊临床特征分析杨旭堃，刘权贤，张娟，贺建清，杨明金，文佳玉四川大学华西医院呼吸与危重症医学科，四川成都6 10 0 0 0摘要目的探讨2 型糖尿病合并肺结核感染患者的初诊临床特征。方法选取四川大学华西医院自2 0 11年1月至2019年12 月收治的8 2 7 例肺结核感染患者为研究对象。根据患者结核分枝杆菌感染状态及是否合并2 型糖尿病将其分为单纯活动性肺结核（ATB)组（n=241）、2 型糖尿病合并活动性肺结核（DM-ATB）组（n=266）、单纯潜伏性肺结核（LTBI）组（n=2 2 0）、2 型糖尿病合并潜伏性肺结核(DM-LTBI)组（n=100）。根据初诊时糖化血红蛋白（HbA1c）数值将2 0 5例2 型糖尿病合并肺结核患者分为A组(HbAlc7%,血糖控制达标单纯活动性肺结核,n=28）、B组（HbA1c7%,血糖控制未达标单纯活动性肺结核,n=120）、C组（HbA1c7%，血糖控制达标潜伏性肺结核,n=14）、D 组（HbA1c7%，血糖控制未达标潜伏性肺结核,n=43）。分别比较DM-ATB组、ATB组、DM-LTBI组、LTBI组与A组、B组、C组、D组患者的人口学基本特征、肺结核相关临床症状、实验室检查结果。结果DM-ATB组患者咳嗽、咯血比例均高于ATB组,胸痛、其他症状比例均低于ATB组,差异均有统计学意义（P0.05）;D M-L T BI组患者发热、咳嗽、胸痛比例均低于LTBI组,差异均有统计学意义（P 0.0 5）。D M-A T B组患者降钙素原、白细胞介素6、血沉、肌酐、胱抑素C均高于ATB组,血小板计数、血红蛋白、白蛋白均低于ATB组,差异均有统计学意义（P0.05）;D M-L T BI组患者 CD4+、白细胞介素6、肌酐、胱抑素 C均高于LTBI组，CD8+、血小板计数、血红蛋白、球蛋白均低于LTBI组,差异均有统计学意义(P0.05）。B组患者咯血症状比例高于A组，差异有统计学意义(P0.05);D组患者胸痛症状比例低于C组,差异有统计学意义(P0.05)。B组患者 CD8+、血沉、血红蛋白、血小板计数均高于A组,差异均有统计学意义(P0.05）。结论降钙素原、血沉升高的活动性肺结核患者应加强血糖及HbA1c筛查,CD8+、血小板计数降低与肌酐、胱抑素C升高可能为2 型糖尿病合并肺结核共病患者的筛查及诊断提供参考性建议。关键词糖尿病；肺结核；结核分枝杆菌；糖化血红蛋白；血小板计数中图分类号：R521;R587.2doi:10.16680/j.1671-3826.2023.08.02文章编号：16 7 1-38 2 6(2 0 2 3)0 8-0 7 7 6-0 6nalysis of clinical characteristics of patients with type 2 diabetes complicated with pulmonary tuberculosis at first diagnosYANG Xu-kun,LIU Quan-xian,ZHANG Juan,HE Jian-qing,YANG Ming-jin,WEN Jia-yu(Department of Respiratory and CCare Medicine,West China Hospital of Sichuan University,Chengdu 610000,China)Abstract:ObjectiveTo investigate the initial clinical features of type 2 diabetes mellitus patients with pulmonary tuberculosis infec-tion.Methods A total of 827 patients with tuberculosis infection admitted to West China Hospital of Sichuan University from January2011 to December 2019 were selected as the study objects.According to the status of mycobacterium tuberculosis infection and whetherpatients were combined with type 2 diabetes,the patients were divided into simple active tuberculosis disease(ATB)group(n=241),type 2 diabetes with diabetes mellitus-active tuberculosis disease(DM-ATB)group(n=266),simple latent tuberculosis infection(LTBI)group(n=220),and type 2 diabetes with diabetes mellitus-latent tuberculosis infection(DM-LTBI)group(n=100).Accord-ing to the HbAlc value at initial diagnosis,205 patients with type 2 diabetes mellitus complicated with pulmonary tuberculosis were di-vided into group A(HbAlc 7%,blood glucose control up to standard with simple active pulmonary tuberculosis,n=28),group B(HbA1c7%,blood glucose control up to standard with simple active pulmonary tuberculosis,n=120),group C(latent pulmonarytuberculosis with HbAlc 7%,blood glucose control up to standard,n=14),and group D(latent pulmonary tuberculosis withHbAlc 7%and substandard blood glucose control,n=43).The basic demographic characteristics,clinical symptoms and laboratorytest results of patients in DM-ATB group,ATB group,DM-LTBI group,LTBI group and groups A,B,C and D were compared,respec-tively.Results The proportion of cough and hemoptysis in DM-ATB group was higher than that in ATB group,and the proportion ofchest pain and other symptoms was lower than that in ATB group,with statistical significance(P0.05).The proportions of fever,基金项目：国家自然科学基金项目（8 18 7 0 0 15）第一作者：杨旭堃（19 8 4-），男，四川成都人，主治医师，硕士通信作者：贺建清，E-mail：j i a n q i n g _h e s c u.e d u.c n777.Clin J Med Offic,Aug,20232023年8 月第51卷第8 期临床军医杂志cough and chest pain in DM-LTBI group were lower than those in LTBI group,and the differences were statistically significant(P0.05).The procalcitonin,interleukin-6,erythrocyte sedimentation rate,creatinine and cystatin-C in DM-ATB group were higher thanthose in ATB group,and the platelet count,hemoglobin and albumin were lower than those in ATB group,with statistical significance(P0.05).CD4+,interleukin-6,creatinine and cystatin-C in DM-LTBI group were higher than those in LTBI group,while CD8+,platelet count,hemoglobin and globulin were lower than those in LTBI group,with statistical significance(P0.05).The proportion ofhemoptysis symptoms in group B was higher than that in group A,and the difference was statistically significant(P0.05).The pro-portion of chest pain symptoms in group D was lower than that in group C,and the difference was statistically significant(P0.05).CD8+,ESR,hemoglobin and platelet count in group B were higher than those in group A,and the differences were statistically signifi-cant(P0.05).Conclusion Blood glucose and HbAlc screening should be strengthened in active pulmonary tuberculosis patientswith procalcitonin and erythrocyte sedimentation rate.CD8+,decreased platelet count and increased creatinine and cystatin-C mayprovide reference recommendations for screening and diagnosis of type 2 diabetes patients with pulmonary tuberculosis comorbiditis.Key words:Diabetes mellitus;Tuberculosis;MMycobacterium tuberculosis;Glycated hemoglobin Alc;Platelet count目前，全球约有4.6 3亿糖尿病患者，至2045年,全球糖尿病患者可能增长至7 亿例 12 糖尿病会增加肺结核的患病风险,并且糖尿病合并肺结核患者早期识别困难、抗结核耐药率高、依从性差、病死率相对较高 3-6 。在糖尿病患者中隐藏较多无症状或症状轻微的结核感染患者，基于可疑症状筛查无法及时发现这些患者，这一现状对结核病的社区防控管理造成极大困难 7-8 。本研究旨在探讨2 型糖尿病合并肺结核感染患者的初诊临床特征，为早期筛查提供参考性建议。现报道如下1对象与方法1.1研究对象选取四川大学华西医院自2 0 11年1月至2 0 19 年12 月收治的8 2 7 例肺结核感染患者为研究对象。纳入标准：初诊住院；符合肺结核诊断和治疗指南中肺结核诊断标准 2 ;符合中国2型糖尿病防治指南(2 0 2 0 年版）中2 型糖尿病诊断标准 3。排除标准：合并除结核分枝杆菌以外的活动性感染；合并免疫缺陷疾病和(或)其他严重器质性疾病；哺乳期或妊娠期女性；合并精神疾病。根据患者结核分枝杆菌感染状态及是否合并2 型糖尿病将患者分为单纯活动性肺结核（active tuber-culosis disease,ATB）组（n=241）、2 型糖尿病合并活动性肺结核（diabetes mellitus-active tuberculosisdisease,DM-ATB）组（n=266）、单纯潜伏性肺结核(latent tuberculosis infection,LTBI）组（n=220）、2 型糖尿病合并潜伏性肺结核（diabetes mellitus-la-tent tuberculosis infection,DM-LTBI)组（n=100)。DM-ATB组与DM-LTBI组患者中,选取2 0 5例进行糖化血红蛋白（glycated hemoglobin Alc,HbAlc）检查。根据初诊时HbA1c数值将患者分为A组(HbA1c7%,血糖控制达标单纯活动性肺结核,n=28）、B组（HbA1c7%，血糖控制未达标单纯活动性肺结核,n=120）、C组（HbA1c7%,血糖控制达标潜伏性肺结核,n=14）、D 组（HbA1c7%，血糖控制未达标潜伏性肺结核，n=43）。本研究经医院伦理委员会批准。所有患者均签署知情同意书。1.2研究方法收集所有患者的临床资料，包括人口学基本特征（性别、年龄、民族分布）、肺结核相关临床症状（发热、咳嗽、咯血、胸痛、其他症状）、实验室检查结果 T细胞、白细胞介素6(interleukin-6,IL-6）、降钙素原（procalcitonin，PCT）、C-反应蛋白(C-reactive protein,CRP)、血沉(erythrocyte sedimen-tationrate，ESR）、白蛋白（albumin，A L B）、球蛋白（g l o b u l i n,G L B）、肌酐（creatinine,CREA）、胱抑素C(cystatin-C,Cys-C）、白细胞计数（white blood cellcount,WBC）、血红蛋白（haemoglobin,Hb）、血小板计数(platelet count,PLT)等。1.3统计学方法采用SPSS26.0统计学软件对数据进行处理。计量资料用均数标准差（xs）表示，组间比较采用t检验。计数资料用例（百分率表示,组间比较采用x检验。以P0.05为差异有统计学意义2丝结果2.1DM-ATB 组、ATB组、DM-LTBI组、LTBI组患者人口学基本特征比较DM-ATB 组、ATB 组、DM-LTBI组、LTBI组各组内性别、年龄、民族分布比较,差异均有统计学意义(P0.05）。见表1。2.2DM-ATB组、ATB组、DM-LTBI组、LTBI组患者肺结核相关临床症状比较DM-ATB组患者咳嗽、咯血比例均高于ATB组,胸痛、其他症状比例均低于ATB组，差异均有统计学意义（P0.05）。778Clin J MedOfficNo.8,Aug,2023临床军医杂志2023年8 月第51卷第8 期DM-LTBI组患者发热、咳嗽、胸痛比例均低于LTBI组,差异均有统计学意义（P40汉族藏族其他民族ATB组(n=241)190(78.8)51(21.2)125(51.9)116(48.1)188(78.0)37(15.4)16(6.6)DM-ATB 组(n=266)233(87.5)33(12.4)31(11.7)235(88.3)236(88.7)18(6.8)12(4.5)LTBI 组(n=220)186(84.5)34(15.5)111(50.5)109(49.5)171(77.7)33(15.0)16(7.3)DM-LTBI 组(n=100)79(79.0)21(21.0)5(5.0)95(95.0)82(82.0)14(14.0)4(4.0)表2DM-ATB组、ATB组、DM-LTBI组、LTBI组患者肺结核相关临床症状比较/例（百分率/%）组别发热咳嗽咯血胸痛其他症状ATB组(n=241)50(20.7)145(60.2)30(12.4)54(22.4)45(18.7)DM-ATB 组(n=266)63(23.7)187(70.3)48(18.0)26(9.8)36(13.5)LTBI 组(n=220)61(27.7)136(61.8)17(7.7)62(28.2)38(17.3)DM-LTBI 组(n=100)16(16.0)37(37.0)8(8.0)10(10.0)20(20.0)注：与ATB组比较，P0.05；与LTBI组比较，P0.052.3DM-ATB组、ATB 组、DM-LTBI组、LTBI组患者实验室检查结果比较DM-ATB 组患者 PCT、IL-6、ESR、CREA、Cy s-C 均高于ATB组,PLT、H b、ALB均低于ATB组，差异均有统计学意义（P0.05）。D M-L T BI 组患者 CD4+、IL-6、CREA、Cy s-C均高于LTBI组，CD8+、PL T、H b、G L B 均低于LTBI组,差异均有统计学意义（P0.05）。见表3。2.4A组、B组、C组、D组患者临床特征比较A组、B组、C组、D组各组内性别、年龄、民族分布比较，差异均有统计学意义（P0.05）。见表4。2.5A组、B组、C组、D组患者临床症状比较交B组患者咯血症状比例高于A组，差异有统计学意义(P0.05）。D 组患者胸痛症状比例低于C 组,差异有统计学意义（P0.05）。见表5。2.66A组、B组、C组、D组患者实验室检查结果比表3DM-ATB组、ATB组、DM-LTBI组、LTBI组患者实验室检查结果比较（xs)组别CD3+CD4+CD8+CRP/mgL-1PCT/ng*ml-1ATB组70.37%10.02%37.93%10.49%27.42%10.09%37.85 42.320.13 0.19DM-ATB组71.03%12.42%39.87%10.23%26.98%10.71%45.87 46.220.51 1.200LTBI 组71.55%9.28%38.41%8.65%27.37%9.04%34.86 44.490.41 1.37DM-LTBI 组69.17%10.09%42.57%9.48%222.88%6.03%31.52 42.280.36 0.61组别WBC/个L-1PLT/g L-1IL-6/pg ml-1Hb/g L-1Cys-C/mg L-1ATB组(6.58 2.85)109(268.06 113.87)10931.89 33.31126.76 21.541.00 0.34DM-ATB组(7.05 2.82)109(223.63 108.01)109 67.91 135.55122.69 22.21 01.14 0.770LTBI 组(6.26 2.92)109(262.51 107.61)10928.79 30.22133.38 21.400.96 0.44DM-LTBI 组(6.30 3.66)109(182.60 95.26)109105.89 199.53 123.86 27.34 1.31 0.99组别ESR/mmh1ALB/gL-1CLB/g L-1CREA/molL-1ATB组50.43 32.4237.82 6.4230.59 6.4566.42 46.55DM-ATB 组57.28 30.82 035.24 6.67030.35 5.9478.76 84.62 LTBI 组42.24 31.2338.055.5230.31 6.6466.14 24.08DM-LTBI组43.77 29.1837.14 7.1828.16 6.65101.69 106.49注：与ATB组比较,P0.05；与LTBI组比较，P40汉族藏族其他民族A组(n=28)25(89.3)3(10.7)2(7.1)26(92.9)23(82.1)4(14.3)1(3.6)B 组(n=120)108(90.0)12(10.0)19(15.8)101(84.2)106(88.4)7(5.8)7(5.8)C组(n=14)12(85.7)2(14.3)0(0)14(100.0)12(85.8)1(7.1)1(7.1)D 组(n=43)32(74.4)11(25.6)4(9.3)39(90.7)34(79.1)7(16.3)2(4.6)表5A组、B组、C组、D组患者临床症状比较/例（百分率/%）组别发热咳嗽咯血胸痛其他症状A组(n=28)7(25.0)15(53.6)2(7.1)1(3.6)5(17.9)B 组(n=120)24(20.0)89(74.2)20(16.7)12(10.0)14(11.7)C 组(n=14)3(21.4)6(42.9)0(0)3(21.4)2(14.3)D 组(n=43)8(18.6)18(41.9)3(7.0)3(7.0)9(20.9)注：与A组比较，P0.05；与C组比较，P0.05较B组患者CD8+、ESR、H b、PL T 均高于A组，差异均有统计学意义（P0.05)。见表6。表6 A组、B组、C组、D组患者实验室检查结果比较(xs)组别CD3+CD4+CD8+CRP/mgL-1PCT/ngml-IA组67.32%14.43%41.00%8.99%22.74%6.87%31.53 37.800.21 0.19B组72.72%11.13%37.87%10.53%30.58%11.85%43.16 38.760.18 0.26C组70.14%9.25%45.46%8.14%20.69%5.73%47.09 45.160.36 0.62D组70.42%8.24%44.22%8.75%22.27%5.57%25.81 39.120.12 0.10组别WBC/个L-1PLT/gL-1IL-6/pg ml-1Hb/g L-1Cys-C/mg L-1A组(7.00 3.89)109(192.43 111.31)10987.57 159.77113.79 28.701.09 0.24B组(7.29 2.83)109(235.02 113.32)10930.53 69.92125.57 20.9401.11 0.72C组(7.07 4.04)109(216.07 108.48)109241.35 364.52117.79 28.391.52 1.29D组(6.36 1.92)109(201.79 96.80)10947.61 68.02132.16 25.911.01 0.41组别ESR/mmh-1ALB/gL-1GLB/g L-1CREA/molL-1A组43.64 24.4334.69 7.8931.16 6.2761.70 22.47B组60.62 27.66034.73 6.7831.03 5.3878.80 89.39C组46.79 25.3737.08 6.6331.40 9.77114.06 109.91D组42.60 30.9337.68 6.3727.63 5.6876.77 45.08注：与A组比较，OP0.053讨论糖尿病患者的固有免疫和获得性免疫功能均受损,导致其对结核分枝杆菌易感 9-10 1。糖尿病患者免疫功能改变包括宿主对结核分枝杆菌识别能力下降、吞噬细胞活性下降，免疫细胞数量减少及IL-1、IL-6、T NF-等细胞因子水平的改变 11-2 有研究报道,PCT在活动性结核感染时上升，且与疾病严重程度呈正相关 13-14。糖尿病导致结核病患者CD4+升高，但CD8+下降，使机体抗结核感染的免疫反应减弱,从而使糖尿病患者的结核感染加重 1-16 。有研究报道,糖尿病导致患者PLT反应性增加及活性增强 17.2 0 。结核病患者常见 PLT轻微增多,且与结核病严重程度及抗结核药物治疗的不良反应有关 2 12 3。有研究报道，相较于单纯性糖尿病和单纯性结核病患者,糖尿病合并结核病患者的血小板体积和压积发生特异性改变 2 4。糖尿下转第7 8 5页）780.ClinJMed Offic,Aug,2023VO临床军医杂志2023年8 月第51卷第8 期病合并结核病患者的抗结核治疗效果及预后均与其血糖控制情况密切相关,即良好的血糖控制能够提高抗结核疗效,缓解结核病的临床症状 2 5-2 6 。血糖控制不佳的糖尿病患者更易罹患结核病,或者导致潜伏性肺结核向活动性肺结核转化，从而表现出更为严重的临床症状 2 7.2 8 本研究结果显示：DM-ATB组患者咳嗽、咯血比例均高于ATB组,胸痛、其他症状比例均低于ATB组,差异均有统计学意义(P0.05）;D M-L T BI 组患者发热、咳嗽、胸痛比例均低于LTBI组,差异均有统计学意义（P0.05）。这提示,2 型糖尿病合并活动性肺结核患者咳嗽、咯血症状明显，而发热、咳嗽、胸痛等呼吸道症状较少出现。本研究结果显示,DM-ATB 组患者 PCT、IL-6、ESR、CREA、Cy s-C均高于ATB组,PLT、H b、A L B均低于ATB组,差异均有统计学意义（P0.05）；D M-L T BI组患者CD4+、IL-6、CREA、Cy s-C均高于LTBI组,CD8+、PLT、H b、G L B均低于LTBI组,差异均有统计学意义(P0.05）。这提示,2 型糖尿病合并肺结核患者的炎症应答增强，营养不良风险增高。此外，B组患者咯血症状比例高于A组,差异有统计学意义(P0.05);D组患者胸痛症状比例低于C组,差异有统计学意义（P0.05）。这提示,与血糖控制良好的活动性肺结核患者比较，血糖控制不佳的活动性肺结核患者更易出现咯血的临床表现,而在2型糖尿病合并潜伏性结核感染患者中临床表现不典型。综上所述,PCT、ESR升高的活动性肺结核患者应加强血糖及HbA1c筛查。CD8+、PL T 降低与CREA、Cy s-C 升高可能为2 型糖尿病合并肺结核患者的筛查及诊断提供参考性建议。参考文献：1 Ali MK,Pearson-Stuttard J,Selvin E,et al.Interpreting globaltrends in type 2 diabetes complications and mortality J.Diabe-tologia,2022,65(1):3-13.2Cho NH,Shaw JE,Karuranga S,et al.IDF diabetes atlas:globalestimates of diabetes prevalence for 2017 and projections for2045J.Diabetes Res Clin Pract,2018,138:271-281.3Foe-Essomba JR,Kenmoe S,Tchatchouang S,et al.Diabetes mel-litus and tuberculosis,a systematic review and meta-analysis withsensitivity analysis for studies comparable for confounders J.PLoS One,2021,16(12):e0261246.4Dooley KE,Chaisson RE.Tuberculosis and diabetes mellitus:con-vergence of two 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