摘要:目的 探討兒童糖尿?。―M)合并尿路感染(UTI)的臨床特征和危險(xiǎn)因素。方法 160例兒童DM患者根據(jù)并發(fā)泌尿系感染分為UTI組和非UTI組,每組80例。收集兒童DM并發(fā)泌尿系感染的臨床資料,包括DM類(lèi)型、性別、年齡、體質(zhì)量指數(shù)(BMI)、病程、住院時(shí)間、是否留置尿管、是否酮癥酸中毒、抗生素及胰島素使用情況、尿液標(biāo)本分離細(xì)菌類(lèi)型及入院時(shí)各項(xiàng)化驗(yàn)指標(biāo)等結(jié)果,并進(jìn)行分析。結(jié)果 UTI組病原菌主要包括大腸埃希菌(37株,46.3%)、腸球菌(21株,26.2%)、肺炎克雷伯菌(9株,11.2%)等。單因素分析顯示2組間肥胖、病程、住院時(shí)間、是否留置導(dǎo)尿管、是否酮癥酸中毒、抗生素使用情況、糖化血紅蛋白(HbA1c)、白蛋白(ALB)及血肌酐(Cr)的差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。多因素分析顯示DM合并UTI的危險(xiǎn)因素包括住院時(shí)間延長(zhǎng)(OR=2.087,95%CI:1.562~2.789)、留置導(dǎo)尿管(OR=15.886,95%CI:2.336~108.007)、酮癥酸中毒(OR=9.300,95%CI:1.169~73.992)、病程≥36個(gè)月(OR=20.548,95%CI:2.425~174.119)、HbA1c升高(OR=16.686,95%CI:3.666~75.955)及血Cr升高(OR=1.010,95%CI:1.002~1.019);而血清ALB升高(OR=0.799,95%CI:0.702~0.910)為其保護(hù)因素。結(jié)論 兒童DM合并UTI以大腸埃希菌感染為主,與住院時(shí)間、留置尿管、酮癥酸中毒、病程時(shí)間、HbA1c、血Cr和ALB水平密切相關(guān)。
關(guān)鍵詞:糖尿??;危險(xiǎn)因素;尿路感染;臨床特征;兒童
中圖分類(lèi)號(hào):R725.871 文獻(xiàn)標(biāo)志碼:A DOI:10.11958/20240181
Analysis of clinical characteristics and risk factors for diabetes mellitus complicated with urinary tract infection in children
NIJAT Alim1,2,3, MA Shifeng2, XAMSIYA Alim3, ZHANG Jing3, ZHENG Rongxiu2△
1 Graduate School of Tianjin Medical University, Tianjin 300070, China; 2 Department of Pediatrics, Tianjin Medical
University General Hospital; 3 Department of Pediatrics, the Urumqi No.1 People’s Hospital (Urumqi Children’s Hospital)
△Corresponding"Author E-mail: rzheng@tmu.edu.cn
Abstract: Objective To investigate clinical features and risk factors of childhood diabetes mellitus (DM) complicated with urinary tract infection (UTI). Methods The data of 160 children with DM in our hospital in the past 2 years were collected as the research object, and they were divided into the UTI group and the non-UTI group UTI, "with 80 cases in each group."The clinical data of children with DM and UTI were collected and analyzed, including DM type, sex, age, body mass index (BMI), living environment, duration of disease, length of hospital stay, indwelling catheter, ketoacidosis, antibiotic and insulin use, the types of bacteria isolated from urine samples and various laboratory indicators on admission. Results Pathogen bacteria mainly included Escherichia coli (n=37, 46.2%), Enterococci (n=21, 26.2%) and Klebsiella pneumoniae (n=9, 11.2%) in the UTI group. Univariate analysis showed that there were significant differences in obesity, duration of disease, length of hospital stay, indwelling catheter, ketoacidosis, antibiotic use, glycosylated hemoglobin (HbA1c), albumin (ALB) and serum creatinine (Cr) between the two groups (P<0.05). Multivariate regression analysis showed that risk factors for DM complicating UTI included prolonged hospitalization (OR=2.087, 95%CI: 1.562-2.789), indwelling urinary catheter (OR=15.886, 95%CI: 2.336-108.007), ketoacidosis (OR=9.300, 95%CI: 1.169-73.992), duration of disease ≥36 months (OR=20.548, 95%CI: 2.425-174.119), increased HbA1c (OR=16.686, 95%CI: 3.666-75.955) and serum Cr (OR=1.010, 95%CI: 1.002-1.019), while the increased serum ALB (OR=0.799, 95%CI: 0.702-0.910) was its protective factor. Conclusion Pathogenic bacteria in the UTI group are mainly Escherichia coli. Children with DM and UTI are closely related to the length of hospitalization, indwelling catheter, ketoacidosis, duration of disease, HbA1c, serum Cr and ALB levels.
Key words: diabetes mellitus; risk factors; urinary tract infection; clinical characteristics; child
國(guó)際糖尿病聯(lián)盟2021年的數(shù)據(jù)顯示,全球糖尿?。―M)患者已達(dá)5.37億,其中120萬(wàn)為18歲以下青少年[1]。兒童主要以1型糖尿?。═1DM)為主,但近年來(lái)2型糖尿?。═2DM)的比例不斷升高[2-3],這主要與不健康飲食結(jié)構(gòu)、缺乏體育運(yùn)動(dòng)、肥胖相關(guān)[4]。除常見(jiàn)的視網(wǎng)膜病變、腎病和神經(jīng)病變外,DM患者發(fā)生感染的風(fēng)險(xiǎn)也較高,主要包括呼吸道感染、皮膚和軟組織感染、尿路感染(urinary tract infection,UTI)及胃腸道感染[5-6]。UTI以無(wú)癥狀性菌尿?yàn)橹饕憩F(xiàn),進(jìn)一步可進(jìn)展為腎盂腎炎、腎膿腫和壞死性腎乳頭炎等急性腎損傷,從而增加慢性腎病的進(jìn)展[7-8]。研究發(fā)現(xiàn),患有UTI的DM患兒的菌血癥風(fēng)險(xiǎn)是非DM患兒的4倍[6,8]。目前關(guān)于兒童DM合并UTI的研究較少,探索其臨床特征及危險(xiǎn)因素對(duì)于制定有效的預(yù)防和治療策略至關(guān)重要。本文旨在分析兒童DM合并UTI的臨床表現(xiàn)和風(fēng)險(xiǎn)因素,提供預(yù)防和治療方案的初步理論指導(dǎo),以降低兒童DM患者UTI發(fā)生率。
1 對(duì)象與方法
1.1 研究對(duì)象 收集2020年1月—2022年1月就診于天津醫(yī)科大學(xué)總醫(yī)院兒科與烏魯木齊市第一人民醫(yī)院(烏魯木齊兒童醫(yī)院)兒科的160例T1DM和T2DM患兒。其中男66例,女94例,年齡3.8~11.0歲,平均(8.9±3.3)歲,T1DM 137例(85.6%),T2DM 23例(14.4%)。病例的選擇方式為首先選取DM伴UTI的患者,再根據(jù)1∶1配比隨機(jī)抽樣同期不伴發(fā)UTI的患者,160例中UTI組和非UTI組各80例。排除標(biāo)準(zhǔn):(1)既往有泌尿系相關(guān)手術(shù)史。(2)本次就診前在其他醫(yī)療機(jī)構(gòu)行相應(yīng)治療。(3)合并原發(fā)性或獲得性免疫缺陷疾?。ㄈ绨滩〉龋?。(4)臨床資料不完整。本研究經(jīng)天津醫(yī)科大學(xué)總醫(yī)院倫理委員會(huì)審查通過(guò)(倫理批號(hào):IRB2024-YX-114-01)。
1.2 研究方法 查閱相關(guān)文獻(xiàn)[9],回顧性收集全部患兒的臨床資料,包括性別、年齡、體質(zhì)量指數(shù)(BMI)、DM類(lèi)型、病程、住院時(shí)間、是否留置尿管、是否合并酮癥酸中毒、抗生素及胰島素使用情況、入院時(shí)實(shí)驗(yàn)室檢查指標(biāo)[空腹血糖(FBG)、糖化血紅蛋白(HbA1c)、白蛋白(ALB)及血肌酐(Cr)]、尿液標(biāo)本培養(yǎng)分離細(xì)菌類(lèi)型等。
1.3 相關(guān)診斷標(biāo)準(zhǔn) DM診斷根據(jù)2020年美國(guó)糖尿病學(xué)會(huì)的診斷標(biāo)準(zhǔn)[10]。UTI診斷標(biāo)準(zhǔn):留取清晨中段尿液15~20 mL,行尿液細(xì)菌培養(yǎng)及藥物敏感試驗(yàn)。依據(jù)《泌尿道感染診治循證指南(2016)》,將尿培養(yǎng)革蘭陰性菌菌落數(shù)≥1×104/mL、革蘭陽(yáng)性菌菌落數(shù)≥1×103/mL和(或)尿常規(guī)白細(xì)胞≥5個(gè)/高倍視野則認(rèn)定為UTI[11]。超重/肥胖診斷標(biāo)準(zhǔn):利用2007版WHO Anthm Plus軟件,依據(jù)患兒年齡和性別,若其BMI百分位數(shù)≥85%但<95%定義為超重,BMI百分位數(shù)≥95%則定義為肥胖[12-13]。DM酮癥酸中毒診斷標(biāo)準(zhǔn):隨機(jī)血糖≥11 mmol/L,pH值≤7.3或HCO3-≤15 mmol/L,血酮體≥3 mmol/L或尿酮≥++[14]。
1.4 統(tǒng)計(jì)學(xué)方法 采用SPSS 24.0軟件進(jìn)行數(shù)據(jù)分析。計(jì)量資料經(jīng)Shapiro-Wilk檢驗(yàn)不符合正態(tài)分布,采用M(P25,P75)表示,組間比較采用Wilcoxon秩和檢驗(yàn);計(jì)數(shù)資料以例(%)表示,組間比較采用χ2檢驗(yàn)。單因素分析篩選潛在影響DM伴發(fā)UTI的影響因素,并納入多因素Logistic回歸模型分析。以P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 UTI組病原菌分布 UTI組尿液培養(yǎng)分離出12種病原菌,共80株,包括大腸埃希菌37株(46.3%),腸球菌21株(26.2%),肺炎克雷伯菌9株(11.2%),產(chǎn)氣腸桿菌5株(6.3%),銅綠假單胞菌、表皮葡萄球菌、摩根氏摩根菌、弗勞地枸櫞酸桿菌、奇異變形桿菌、檸檬酸桿菌、腐生葡萄球菌、嗜麥芽窄食單胞菌各1株。
2.2 UTI組和非UTI組臨床資料比較 2組患者性別、年齡、DM類(lèi)型、是否胰島素治療差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05),與非UTI組相比,UTI組肥胖、留置導(dǎo)尿管、酮癥酸中毒、病程≥36個(gè)月比例升高,住院時(shí)間長(zhǎng),F(xiàn)BG、HbA1c和血Cr水平升高,抗生素使用率、ALB水平下降,住院費(fèi)用增加(P<0.05)。見(jiàn)表1。
2.3 影響DM合并UTI的多因素分析 將單因素分析中篩選可能潛在影響DM合并UTI的11項(xiàng)因素作為自變量:BMI分組(非超重/肥胖=0,超重=1,肥胖=2)、病程(<6個(gè)月=1,6~<12個(gè)月=2,12~<36個(gè)月=3,≥36個(gè)月=4)、住院時(shí)間、住院費(fèi)用、留置導(dǎo)尿管(是=1,否=0)、酮癥酸中毒(是=1,否=0)、抗生素(使用=1,未使用=0)及入院時(shí)化驗(yàn)指標(biāo)(FBG、HbA1c、ALB、血Cr),以是否合并UTI作為因變量(合并UTI=1,未合并UTI=0),進(jìn)行多因素Logistic回歸分析。結(jié)果顯示DM合并UTI的危險(xiǎn)因素包括住院時(shí)間較長(zhǎng)、留置導(dǎo)尿管、合并酮癥酸中毒、HbA1c升高、病程≥36個(gè)月、血Cr升高,而血清ALB升高為其保護(hù)因素,見(jiàn)表2。
3 討論
DM患者由于代謝紊亂導(dǎo)致糖、脂肪、蛋白質(zhì)失衡,易發(fā)生感染。而DM可能會(huì)增加UTI的風(fēng)險(xiǎn),主要考慮以下因素:(1)長(zhǎng)期高水平血糖可導(dǎo)致尿糖升高,尿儲(chǔ)留使得尿液成為細(xì)菌生長(zhǎng)的溫床,有利于細(xì)菌的生長(zhǎng)繁殖,增加感染風(fēng)險(xiǎn),這也是DM患者并發(fā)UTI且治療后易復(fù)發(fā)的主要原因[6]。(2)DM可引起免疫功能低下,減弱機(jī)體抵抗感染的能力。有文獻(xiàn)報(bào)道DM合并免疫缺陷是UTI的誘發(fā)因素[15]。炎癥的易感性可能與機(jī)體的免疫功能相關(guān),DM可以改變體內(nèi)的免疫狀態(tài),從而導(dǎo)致炎癥細(xì)胞的失調(diào),其中,單核細(xì)胞和多形核白細(xì)胞促炎細(xì)胞因子的上調(diào)以及巨噬細(xì)胞相關(guān)生長(zhǎng)因子的下調(diào)可能導(dǎo)致機(jī)體免疫抵抗力下降,從而增加感染的風(fēng)險(xiǎn)[16]。(3)長(zhǎng)期高血糖還可能導(dǎo)致膀胱功能障礙[17],使膀胱排空不完全,尿潴留誘導(dǎo)細(xì)菌生長(zhǎng),從而增加感染風(fēng)險(xiǎn)。據(jù)文獻(xiàn)報(bào)道,因感染住院的DM患者是正常成年人的4倍[18]。作為最常見(jiàn)的感染性疾病,分析UTI的危險(xiǎn)因素對(duì)DM患者尤為重要。
Tang等[19]研究發(fā)現(xiàn),引起DM患兒發(fā)生UTI的主要病原菌是大腸埃希菌,這與本研究的結(jié)果相似。以大腸埃希菌為代表的革蘭陰性病原菌中的耐藥菌株發(fā)生率高[20],部分廣譜抗生素可能治療效果不佳,應(yīng)結(jié)合經(jīng)驗(yàn)預(yù)防性使用抗菌藥物或根據(jù)尿培養(yǎng)及藥敏結(jié)果選擇合適的抗生素治療。此外,在本研究中,UTI患兒住院費(fèi)用明顯高于非UTI者,該結(jié)果顯示了預(yù)防DM患兒發(fā)生UTI的重要性。
本研究顯示,病程長(zhǎng)的患者容易發(fā)生UTI,同時(shí)UTI組的HbA1c水平高于非UTI組,分析原因?yàn)殡S著DM病程的延長(zhǎng),機(jī)體葡萄糖利用率降低,蛋白質(zhì)合成功能減弱,ALB需求量增加、合成減少、分解代謝加速,導(dǎo)致負(fù)氮平衡,使組織修復(fù)能力和抵抗細(xì)菌感染的能力減弱[21]。而長(zhǎng)期高血糖水平可使機(jī)體中性粒細(xì)胞的吞噬、抗菌能力降低,增加感染機(jī)會(huì)[22]。同時(shí),病程越長(zhǎng),越容易引起周?chē)窠?jīng)病變,導(dǎo)致松弛性膀胱,排尿功能障礙,大量葡萄糖從腎小球?yàn)V過(guò)時(shí),尿中葡萄糖為細(xì)菌提供了豐富的營(yíng)養(yǎng)源,誘導(dǎo)細(xì)菌繁殖,從而引起UTI的發(fā)生[23]。此時(shí)往往需要反復(fù)導(dǎo)尿。
本研究顯示,留置導(dǎo)尿管是發(fā)生UTI的風(fēng)險(xiǎn)因素之一。留置導(dǎo)尿管可能使尿道正常菌群失調(diào),導(dǎo)尿操作不慎導(dǎo)致尿道和膀胱黏膜物理?yè)p傷,容易成為細(xì)菌的侵襲目標(biāo)。同時(shí),留置導(dǎo)尿管時(shí),尿液不能排干凈,尿液滯留不僅為細(xì)菌提供了繁殖環(huán)境,還可能增加尿液向上反流到腎臟的風(fēng)險(xiǎn),引發(fā)逆行尿路感染。其次,導(dǎo)尿管表面容易形成細(xì)菌生物膜,生物膜內(nèi)的細(xì)菌對(duì)抗生素具有更高的抵抗力,使得感染更加難以治療[24-25]。有研究發(fā)現(xiàn),高達(dá)80%的UTI由留置導(dǎo)尿管引起[24],若炎癥控制欠佳,則會(huì)引起DM等一系列并發(fā)癥的發(fā)生。
DM急性并發(fā)癥以酮癥酸中毒多見(jiàn)[26]。本研究結(jié)果顯示,UTI組酮癥酸中毒發(fā)生比例和血Cr水平明顯高于非UTI組。DM兒童血Cr水平升高表明存在腎功能損傷,這可能降低泌尿系統(tǒng)的防御功能[27],使細(xì)菌更易侵入和定植,從而增加UTI的風(fēng)險(xiǎn),也有可能是UTI帶來(lái)的結(jié)果。因此,在DM患者住院期間,應(yīng)根據(jù)本研究中篩選的UTI相關(guān)危險(xiǎn)因素及時(shí)采取相應(yīng)的預(yù)防措施,如做好健康宣教,嚴(yán)格控制留置導(dǎo)尿管的適應(yīng)證及時(shí)間,積極檢測(cè)/控制血糖避免出現(xiàn)酮癥酸中毒等。
本研究結(jié)果顯示住院時(shí)間長(zhǎng)是兒童DM合并UTI的獨(dú)立危險(xiǎn)因素。因?yàn)樽≡簳r(shí)間的延長(zhǎng)導(dǎo)致患者有更多的機(jī)會(huì)接觸醫(yī)院環(huán)境內(nèi)的病原菌,尤其是耐藥菌,增加了感染的風(fēng)險(xiǎn)。同時(shí),住院期間也有可能因院內(nèi)感染發(fā)生UTI,從而導(dǎo)致住院時(shí)間延長(zhǎng)。既往已有研究表明,住院時(shí)間長(zhǎng)是成人DM合并UTI的危險(xiǎn)因素[28-29]。因此,應(yīng)盡可能縮短DM患者住院時(shí)間,做好宣教,避免院內(nèi)感染的發(fā)生,從而減輕患者經(jīng)濟(jì)壓力。有文獻(xiàn)報(bào)道DM住院咨詢、DM教育計(jì)劃可以有效縮短住院時(shí)間[30],在臨床實(shí)踐中應(yīng)加以重視。
肥胖可能會(huì)增加UTI的風(fēng)險(xiǎn)。因肥胖患者體內(nèi)炎性細(xì)胞因子數(shù)量減少引發(fā)自然殺傷細(xì)胞功能障礙,減弱巨噬細(xì)胞和樹(shù)突狀細(xì)胞的功能,對(duì)病原體抗炎反應(yīng)不足,使得人體抵御病原體能力降低,從而導(dǎo)致DM患者發(fā)生UTI的風(fēng)險(xiǎn)增加[31-32]。既往在成人中進(jìn)行的研究結(jié)果表明,肥胖患者發(fā)生UTI的風(fēng)險(xiǎn)是正常體質(zhì)量患者的2.5倍[33]。同時(shí),一項(xiàng)納入86 638例患者的研究顯示,肥胖的女性患兒比正常體質(zhì)量的女性患兒發(fā)生UTI的風(fēng)險(xiǎn)增加了45%[31]。在本研究中兒童DM的類(lèi)型以T1DM為主(85.6%),此結(jié)論與以往研究基本相同[2]。但超重或肥胖并非兒童DM合并UTI的獨(dú)立危險(xiǎn)因素,這可能是因?yàn)楸狙芯考{入的研究對(duì)象以TIDM為主,其中僅有13.8%(22/160)患者存在肥胖。因此,關(guān)于肥胖是否會(huì)增加DM兒童出現(xiàn)UTI的風(fēng)險(xiǎn)仍需更大樣本量的研究進(jìn)一步論證。
本研究存在一定局限性。首先,本研究為回顧性研究,數(shù)據(jù)收集不夠充分全面;其次,由于納入的研究人群有限,本文沒(méi)有按照DM類(lèi)型及UTI類(lèi)型進(jìn)行亞組分析。因此,本研究的結(jié)論應(yīng)謹(jǐn)慎地解釋,需要研究設(shè)計(jì)更完善、樣本量更充足的前瞻性研究進(jìn)一步論證。
綜上所述,兒童DM患兒易合并UTI,可能與住院時(shí)間、留置尿管、酮癥酸中毒、病程、HbA1c、血Cr和ALB水平有關(guān)。應(yīng)針對(duì)上述影響因素進(jìn)行防治,如采取DM住院咨詢及住院DM宣教等方式,以降低其住院期間發(fā)生UTI的風(fēng)險(xiǎn)。
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(2024-02-10收稿 2024-03-30修回)
(本文編輯 胡小寧)
基金項(xiàng)目:天津市醫(yī)學(xué)重點(diǎn)學(xué)科(專科)建設(shè)項(xiàng)目(TJYXZDXK-068C);天津市衛(wèi)生健康委衛(wèi)生健康科技項(xiàng)目(TJWJ2022XK008)
作者單位:1天津醫(yī)科大學(xué)研究生院(郵編300070);2天津醫(yī)科大學(xué)總醫(yī)院兒科;3烏魯木齊市第一人民醫(yī)院(烏魯木齊兒童醫(yī)院)兒科
作者簡(jiǎn)介:尼加提·阿力木(1990),男,碩士在讀,主要從事兒童內(nèi)分泌相關(guān)研究。E-mail:nijatjan@tmu.edu.cn
△通信作者 E-mail:rzheng@tmu.edu.cn