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Article(id=1241065992634290740, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241065978004557893, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202407403, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1721577600000, receivedDateStr=2024-07-22, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773822790534, onlineDateStr=2026-03-18, pubDate=1740412800000, pubDateStr=2025-02-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773822790534, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773822790534, creator=13701087609, updateTime=1773822790534, updator=13701087609, issue=Issue{id=1241065978004557893, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='4', pageStart='577', pageEnd='768', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773822787047, creator=13701087609, updateTime=1773823194927, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241067688831808347, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241065978004557893, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241067688831808348, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241065978004557893, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=742, endPage=748, ext={EN=ArticleExt(id=1241065993020166735, articleId=1241065992634290740, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Study on the mediating effect of glycated hemoglobin on the association between body mass index and thyroid nodule, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To explore the mediating effect of glycated hemoglobin (HbA1c) on the association between body mass index (BMI) and thyroid nodules, and analyze the mechanisms of how an increase in BMI contributes to the development of thyroid nodules.

Methods

We selected 1 627 individuals who underwent health examinations at a hospital in Shenzhen from December 2020 to October 2023. Demographic data, physical examination, and biochemical test information were collected. Logistic regression was used to analyze the association between BMI, HbA1c, and thyroid nodules. The bootstrap method was used to assess the mediating effect of HbA1c on the relationship between BMI and thyroid nodules.

Results

Among the 1 627 participants, there were 520 males and 1 107 females, with males and females accounting for 32.0% and 68.0% of the sample, respectively. The detection rate of thyroid nodules was 40.9% (666/1 627). Significant differences (P<0.05) were observed between the nodule group and the non-nodule group in terms of age, BMI, occupation, education level, salt intake, HbA1c, and alkaline phosphatase levels. Multivariate analysis indicated that elevated BMI and HbA1c levels were risk factors for thyroid nodules, with OR(95% CI) of 1.038 (1.002-1.075) and 1.297(1.060-1.587), respectively. Mediation analysis showed that HbA1c partially mediated the effect of BMI on the prevalence of thyroid nodules (β=0.018, 95% CI [0.007 - 0.035]), with the mediating effect of HbA1c accounting for 31.58% of the total effect.

Conclusion

BMI and HbA1c are influencing factors of the risk of thyroid nodules, with HbA1c partially mediating the impact of BMI on the incidence of thyroid nodules.

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目的

探讨糖化血红蛋白（Glycated hemoglobin，HbA1c）在身体质量指数（Body Mass Index，BMI）与甲状腺结节关联的中介效应，分析BMI升高对甲状腺结节患病的影响机制。

方法

选取2020年12月至2023年10月在深圳市某三甲医院体检的1 627名研究对象，收集其人口学、体格检查和生化检测等信息，采用logistic回归分析BMI、HbA1c与甲状腺结节的关联；采用bootstrap法评估HbA1c在BMI与甲状腺结节关联的中介效应。

结果

1 627名研究对象中男性520人，女性1 107人，男女占比分别为32.0%和68.0%，甲状腺结节检出率为40.9%（666/1 627）。结节组与非结节组的年龄、BMI、职业、文化程度、食盐摄入情况、HbA1c、碱性磷酸酶水平差异均有统计学意义（P<0.05）。多因素分析显示，BMI和HbA1c水平升高均为甲状腺结节的危险因素，OR（95% CI）分别为1.038（1.002~1.075）和1.297（1.060~1.587）。中介效应分析表明HbA1c部分介导了BMI对甲状腺结节患病的影响（β=0.018，95% CI〔0.007~0.035〕），HbA1c在BMI与甲状腺结节关联间的中介效应占比为31.58%。

结论

BMI和HbA1c是甲状腺结节发生风险的影响因素，HbA1c部分介导了BMI对甲状腺结节发病率的影响。

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张建清与宋嘉宜为共同通信作者。张建清，E-mail：；
宋嘉宜，E-mail：
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朱路与李冠澎为共同第一作者。

朱路（1998—），男，硕士在读，研究方向：公共卫生

李冠澎（1995—），男，博士在读，研究方向：人工智能与生物医学

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朱路（1998—），男，硕士在读，研究方向：公共卫生

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Frontiers in Immunology, 2023, 14: 1219598., articleTitle=Diabetic complications and prospective immunotherapy, refAbstract=null)], funds=[Fund(id=1241066004885852244, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, awardId=22176132, language=CN, fundingSource=国家自然科学基金面上项目(22176132), fundOrder=null, country=null), Fund(id=1241066004990709847, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, awardId=JCYJ20210324135000001, language=CN, fundingSource=深圳市科创委面上项目(JCYJ20210324135000001), fundOrder=null, country=null), Fund(id=1241066005078790236, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, awardId=20221119115615564, language=CN, fundingSource=广东省医学科研基金(20221119115615564), fundOrder=null, country=null), Fund(id=1241066005162676320, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, awardId=B2403008, language=CN, fundingSource=深圳市医科院项目(B2403008), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241065995868099273, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, xref=1., ext=[AuthorCompanyExt(id=1241065995876487883, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, companyId=1241065995868099273, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Academy of Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, China), AuthorCompanyExt(id=1241065995884876492, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, companyId=1241065995868099273, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.山西医科大学医学科学院，山西 太原 030001)]), AuthorCompany(id=1241065996002317017, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, xref=2., ext=[AuthorCompanyExt(id=1241065996006511322, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, companyId=1241065996002317017, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南方科技大学公共卫生及应急管理学院)]), AuthorCompany(id=1241065996098786021, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, xref=3., ext=[AuthorCompanyExt(id=1241065996107174630, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, companyId=1241065996098786021, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.深圳市疾病预防控制中心)])], figs=[ArticleFig(id=1241066002025336846, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=EN, label=Fig.1, caption=Univariate Logistic Analysis of Factors Influencing Thyroid Nodules, figureFileSmall=fNchaOZwMo13PUSlFthYRQ==, figureFileBig=p/jMD/m1Fnr1WUT7igY+qg==, tableContent=null), ArticleFig(id=1241066002159554584, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=CN, label=图1, caption=甲状腺结节影响因素的单因素logistic分析

注：*表示P<0.05。

, figureFileSmall=fNchaOZwMo13PUSlFthYRQ==, figureFileBig=p/jMD/m1Fnr1WUT7igY+qg==, tableContent=null), ArticleFig(id=1241066002432184353, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=EN, label=Fig.2, caption=Mediation Analysis of Glycated Hemoglobin in the Association Between BMI and Thyroid Nodules, figureFileSmall=SXGSoMrXjkvV9mTZZ+z3pQ==, figureFileBig=Y9xNMtFZ72QAa1N+gN5L+Q==, tableContent=null), ArticleFig(id=1241066002574790697, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=CN, label=图2, caption=糖化血红蛋白在BMI和甲状腺结节关联间的中介效应分析, figureFileSmall=SXGSoMrXjkvV9mTZZ+z3pQ==, figureFileBig=Y9xNMtFZ72QAa1N+gN5L+Q==, tableContent=null), ArticleFig(id=1241066004067962924, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=EN, label=Table 1, caption=

Comparison of Basic Characteristics of Study Participants

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总人群(n=1 627 )结节组(n=666 )非结节组(n=961 )Z/χ2P值
年龄[n(%)]37.857<0.001
成年人1 549(95.2)608(91.3)941(97.9)
老年人78(4.8)58(8.7)20(2.1)
性别[n(%)]2.2450.134
男520(32.0)199(29.9)321(33.4)
女1 107(68.0)467(70.1)640(66.6)
BMI(kg/m2)[M(P25，P75 )]22.66(20.58,25.24)22.86(20.81,25.33)22.52(20.45,25.16)-2.5500.011
BMI[n(%)]14.1920.003
偏瘦97(6.0)23(3.5)74(7.7)
正常920(56.5)375(56.3)545(56.7)
超重470(28.9)206(30.9)264(27.5)
肥胖140(8.6)62(9.3)78(8.1)
职业[n(%)]15.3730.004
文职人员433(26.6)169(25.4)264(27.5)
技术人员636(39.1)237(35.6)399(41.5)
服务人员139(8.5)57(8.6)82(8.5)
家务27(1.7)16(2.4)11(1.1)
其他392(24.1)187(28.1)205(21.3)
文化程度[n(%)]12.0620.007
初中及以下87(5.3)45(6.8)42(4.4)
高中及中专139(8.5)62(9.3)77(8.0)
大专及本科1 164(71.5)482(72.4)682(71.0)
研究生及以上237(14.6)77(11.6)160(16.6)
吸烟[n(%)]0.0900.765
无1 383(85.0)564(84.7)819(85.2)
有244(15.0)102(15.3)142(14.8)
饮酒[n(%)]0.0250.873
无1 366(84.0)558(83.8)808(84.1)
有261(16.0)108(16.2)153(15.9)
食盐摄入情况[n(%)]13.2380.001
加碘盐1 299(79.8)504(75.7)795(82.7)
非加碘盐247(15.2)126(18.9)121(12.6)
其他（如硒盐等）81(5.0)36(5.4)45(4.7)
HbA1c(%)[M(P25，P75 )]5.4(5.1,5.6)5.4(5.2,5.7)5.3(5.1,5.5)-4.997<0.001
碱性磷酸酶(U/L)[M(P25，P75 )]63(52,77)65(54,79)61(50,74)-2.5580.011
), ArticleFig(id=1241066004181209139, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=CN, label=表1, caption=

研究对象基本特征比较

, figureFileSmall=null, figureFileBig=null, tableContent=
变量总人群(n=1 627 )结节组(n=666 )非结节组(n=961 )Z/χ2P值
年龄[n(%)]37.857<0.001
成年人1 549(95.2)608(91.3)941(97.9)
老年人78(4.8)58(8.7)20(2.1)
性别[n(%)]2.2450.134
男520(32.0)199(29.9)321(33.4)
女1 107(68.0)467(70.1)640(66.6)
BMI(kg/m2)[M(P25，P75 )]22.66(20.58,25.24)22.86(20.81,25.33)22.52(20.45,25.16)-2.5500.011
BMI[n(%)]14.1920.003
偏瘦97(6.0)23(3.5)74(7.7)
正常920(56.5)375(56.3)545(56.7)
超重470(28.9)206(30.9)264(27.5)
肥胖140(8.6)62(9.3)78(8.1)
职业[n(%)]15.3730.004
文职人员433(26.6)169(25.4)264(27.5)
技术人员636(39.1)237(35.6)399(41.5)
服务人员139(8.5)57(8.6)82(8.5)
家务27(1.7)16(2.4)11(1.1)
其他392(24.1)187(28.1)205(21.3)
文化程度[n(%)]12.0620.007
初中及以下87(5.3)45(6.8)42(4.4)
高中及中专139(8.5)62(9.3)77(8.0)
大专及本科1 164(71.5)482(72.4)682(71.0)
研究生及以上237(14.6)77(11.6)160(16.6)
吸烟[n(%)]0.0900.765
无1 383(85.0)564(84.7)819(85.2)
有244(15.0)102(15.3)142(14.8)
饮酒[n(%)]0.0250.873
无1 366(84.0)558(83.8)808(84.1)
有261(16.0)108(16.2)153(15.9)
食盐摄入情况[n(%)]13.2380.001
加碘盐1 299(79.8)504(75.7)795(82.7)
非加碘盐247(15.2)126(18.9)121(12.6)
其他（如硒盐等）81(5.0)36(5.4)45(4.7)
HbA1c(%)[M(P25，P75 )]5.4(5.1,5.6)5.4(5.2,5.7)5.3(5.1,5.5)-4.997<0.001
碱性磷酸酶(U/L)[M(P25，P75 )]63(52,77)65(54,79)61(50,74)-2.5580.011
), ArticleFig(id=1241066004357369915, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=EN, label=Table 2, caption=

Multivariate Logistic Regression Analysis of the Association Between BMI and Thyroid Nodule Prevalence

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模型变量βWald χ2OR值（95% CI）P值
模型1BMI0.035.401.035(1.005~1.065)0.020
模型2BMI0.0510.011.054(1.020~1.088)0.002
模型3BMI0.044.271.038(1.002~1.075)0.039
), ArticleFig(id=1241066004483199037, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241065992634290740, language=CN, label=表2, caption=

BMI与甲状腺结节患病关系的多因素logistic回归分析

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模型变量βWald χ2OR值（95% CI）P值
模型1BMI0.035.401.035(1.005~1.065)0.020
模型2BMI0.0510.011.054(1.020~1.088)0.002
模型3BMI0.044.271.038(1.002~1.075)0.039
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Multivariate Logistic Regression Analysis of the Association Between HbA1c and Thyroid Nodule Prevalence

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模型变量βWald χ2OR值（95% CI）P值
模型1HbA1c0.3914.891.480(1.213~1.807)<0.001
模型2HbA1c0.329.641.375(1.125~1.680)0.002
模型3HbA1c0.266.381.297(1.060~1.587)0.012
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HbA1c与甲状腺结节患病关系的多因素logistic回归分析

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模型变量βWald χ2OR值（95% CI）P值
模型1HbA1c0.3914.891.480(1.213~1.807)<0.001
模型2HbA1c0.329.641.375(1.125~1.680)0.002
模型3HbA1c0.266.381.297(1.060~1.587)0.012
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糖化血红蛋白在身体质量指数与甲状腺结节患病关联作用的中介效应研究
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朱路 1, 3 , 李冠澎 2 , 湛梓剑 3 , 周晨雨 3 , 陈洋 3 , 陆锦萍 3 , 孔令权 3 , 卓兰 3 , 宋嘉宜 3 , 张建清 1, 3
现代预防医学 | 临床与预防 2025,52(4): 742-748
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现代预防医学 | 临床与预防 2025, 52(4): 742-748
糖化血红蛋白在身体质量指数与甲状腺结节患病关联作用的中介效应研究
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朱路1, 3, 李冠澎2, 湛梓剑3, 周晨雨3, 陈洋3, 陆锦萍3, 孔令权3, 卓兰3, 宋嘉宜3 , 张建清1, 3
作者信息
  • 1.山西医科大学医学科学院，山西 太原 030001
  • 2.南方科技大学公共卫生及应急管理学院
  • 3.深圳市疾病预防控制中心

    • 朱路（1998—），男，硕士在读，研究方向：公共卫生

    李冠澎（1995—），男，博士在读，研究方向：人工智能与生物医学

通讯作者:

张建清与宋嘉宜为共同通信作者。张建清，E-mail：；
宋嘉宜，E-mail：
Study on the mediating effect of glycated hemoglobin on the association between body mass index and thyroid nodule
Lu ZHU1, 3, Guan-peng LI2, Zi-jian ZHAN3, Chen-yu ZHOU3, Yang CHEN3, Jin-ping LU3, Ling-quan KONG3, Lan ZHUO3, Jia-yi SONG3 , Jian-qing ZHANG1, 3
Affiliations
  • Academy of Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi 030001, China
出版时间: 2025-02-25 doi: 10.20043/j.cnki.MPM.202407403
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摘要
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目的

探讨糖化血红蛋白（Glycated hemoglobin，HbA1c）在身体质量指数（Body Mass Index，BMI）与甲状腺结节关联的中介效应，分析BMI升高对甲状腺结节患病的影响机制。

方法

选取2020年12月至2023年10月在深圳市某三甲医院体检的1 627名研究对象，收集其人口学、体格检查和生化检测等信息，采用logistic回归分析BMI、HbA1c与甲状腺结节的关联；采用bootstrap法评估HbA1c在BMI与甲状腺结节关联的中介效应。

结果

1 627名研究对象中男性520人，女性1 107人，男女占比分别为32.0%和68.0%，甲状腺结节检出率为40.9%（666/1 627）。结节组与非结节组的年龄、BMI、职业、文化程度、食盐摄入情况、HbA1c、碱性磷酸酶水平差异均有统计学意义（P<0.05）。多因素分析显示，BMI和HbA1c水平升高均为甲状腺结节的危险因素，OR（95% CI）分别为1.038（1.002~1.075）和1.297（1.060~1.587）。中介效应分析表明HbA1c部分介导了BMI对甲状腺结节患病的影响（β=0.018，95% CI〔0.007~0.035〕），HbA1c在BMI与甲状腺结节关联间的中介效应占比为31.58%。

结论

BMI和HbA1c是甲状腺结节发生风险的影响因素，HbA1c部分介导了BMI对甲状腺结节发病率的影响。

糖化血红蛋白  /  身体质量指数  /  甲状腺结节
Objective

To explore the mediating effect of glycated hemoglobin (HbA1c) on the association between body mass index (BMI) and thyroid nodules, and analyze the mechanisms of how an increase in BMI contributes to the development of thyroid nodules.

Methods

We selected 1 627 individuals who underwent health examinations at a hospital in Shenzhen from December 2020 to October 2023. Demographic data, physical examination, and biochemical test information were collected. Logistic regression was used to analyze the association between BMI, HbA1c, and thyroid nodules. The bootstrap method was used to assess the mediating effect of HbA1c on the relationship between BMI and thyroid nodules.

Results

Among the 1 627 participants, there were 520 males and 1 107 females, with males and females accounting for 32.0% and 68.0% of the sample, respectively. The detection rate of thyroid nodules was 40.9% (666/1 627). Significant differences (P<0.05) were observed between the nodule group and the non-nodule group in terms of age, BMI, occupation, education level, salt intake, HbA1c, and alkaline phosphatase levels. Multivariate analysis indicated that elevated BMI and HbA1c levels were risk factors for thyroid nodules, with OR(95% CI) of 1.038 (1.002-1.075) and 1.297(1.060-1.587), respectively. Mediation analysis showed that HbA1c partially mediated the effect of BMI on the prevalence of thyroid nodules (β=0.018, 95% CI [0.007 - 0.035]), with the mediating effect of HbA1c accounting for 31.58% of the total effect.

Conclusion

BMI and HbA1c are influencing factors of the risk of thyroid nodules, with HbA1c partially mediating the impact of BMI on the incidence of thyroid nodules.

HbA1c  /  BMI  /  Thyroid nodules
朱路, 李冠澎, 湛梓剑, 周晨雨, 陈洋, 陆锦萍, 孔令权, 卓兰, 宋嘉宜, 张建清. 糖化血红蛋白在身体质量指数与甲状腺结节患病关联作用的中介效应研究. 现代预防医学, 2025 , 52 (4) : 742 -748 . DOI: 10.20043/j.cnki.MPM.202407403
Lu ZHU, Guan-peng LI, Zi-jian ZHAN, Chen-yu ZHOU, Yang CHEN, Jin-ping LU, Ling-quan KONG, Lan ZHUO, Jia-yi SONG, Jian-qing ZHANG. Study on the mediating effect of glycated hemoglobin on the association between body mass index and thyroid nodule[J]. Modern Preventive Medicine, 2025 , 52 (4) : 742 -748 . DOI: 10.20043/j.cnki.MPM.202407403
正文
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1　前言
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甲状腺是人体重要的内分泌器官，与人体新陈代谢、身体发育等密切相关。甲状腺结节是指由甲状腺细胞的异常、局灶性生长引起的离散病变，是最为多见的甲状腺疾病[1]。现有研究表明，甲状腺结节受多种因素共同影响，其与电离辐射、年龄、代谢、环境及遗传等因素等相关[2]。美国一项研究估计全球范围内普通人群中甲状腺结节的患病率可达67%以上[3]。而国内一项针对全国的荟萃分析显示，成人体检中甲状腺结节的平均检出率从2008年的29.8%上升到2014年的41.3%，呈显著上升趋势[4]。杭州2021年的一项研究发现，当地1 920例中青年体检者中甲状腺结节检出率为32.9%[4]。甲状腺结节的发病率持续性升高已成为一个不容忽视的公共卫生问题，且其中7%~15%的良性结节会恶变为甲状腺癌[6]。据估计，甲状腺癌患者每年的直接医疗费用可能高达10亿元人民币，给社会和个人都带来了很大的疾病负担[7]。因此，亟需深入研究甲状腺结节的患病危险因素，构建一套实用、可靠和高效的甲状腺结节和甲状腺癌的防控策略提供科学依据，这对于进行甲状腺疾病的早期预警监测、干预和提升公众健康具有重要的科学意义和实用价值。
目前，甲状腺结节的发现与诊断主要依靠甲状腺超声检查及超声引导细针穿刺（Ultrasound-guided fine needle aspiration cytology，US-FNAC），目前的检查手段主要集中在结节的发现和诊断阶段，无法在结节形成之前进行预防性检查。需要发展能够在结节形成之前进行早期预警的技术手段，结合风险因素筛查进行分层和健康监测。身体质量指数（Body Mass Index，BMI）是常用的衡量人体胖瘦程度的一个标准，并已被广泛应用于人体糖脂代谢健康状态的风险评估和糖尿病、高血压、冠状动脉粥样硬化等疾病的风险预测[8]。人群研究表明，BMI的异常变化（如超重或肥胖）可能伴随着血糖、血脂等多种指标代谢异常，这些异常可能间接或直接地影响甲状腺的健康状态，进而导致甲状腺结节的发生[9]。而糖化血红蛋白（Glycated hemoglobin，HbA1c）是临床常用的血糖监测指标，它可以稳定地反映出患者在过去 8~12 周的平均血糖水平，其水平的升高与高血糖、高胰岛素血症、胰岛素抵抗等异常代谢状态密切相关，而这些异常代谢状态可能会导致甲状腺结节的发生和发展[10]。已有研究发现，肥胖者的HbA1c水平显著高于正常体重者[11]，一方面，肥胖者由于胰岛素抵抗以及胰岛素分泌不足，可能导致HbA1c水平升高；另一方面，长期的高血糖状态可能也会加剧胰岛素抵抗，形成恶性循环，导致BMI水平升高[12]。这表明，BMI、HbA1c水平与甲状腺结节三者之间存在复杂的关联，有关HbA1c是否在BMI与甲状腺结节关联间发挥其中介效应，国内外尚未见相关研究。因此，本研究拟探讨体检人群中BMI、HbA1c水平与甲状腺结节之间的关联，进一步分析HbA1c对BMI和甲状腺结节关联间的中介效应，揭示BMI、HbA1c和甲状腺结节之间的相互关联，为甲状腺结节的防治提供早期预警监测参考，最终为制定合理可行、易于推广应用的综合防控策略提供科学依据。
2　资料与方法
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2.1　研究对象
基于已有文献，深圳市居民甲状腺结节的患病率为35.3%[13]。我们使用横断面研究样本量计算公式，计算本研究的样本量：，其中P=0.353（预估患病率为 35.3%），Z=1.96（对应95%的置信水平），d=0.025。根据计算，样本量最低为1 404人，为了提高研究的统计效力，最终选取2020年12月至2023年10月在深圳市罗湖区人民医院体检的1 627名研究对象。纳入标准：年龄≥18周岁；调查前1年在深圳居住不少于6个月；自愿参与此次调查并签署知情同意书。排除标准：患有严重心、肝、肾疾病者；服用过碘剂或做过甲状腺部分、全切术者；处于孕期或哺乳期、近期服用激素、长期服用影响新陈代谢药物者；缺少人口学信息者。本项目由深圳市疾病预防控制中心伦理委员会审批通过（深疾伦字〔2019〕第012A号），所有对象均已签署知情同意书。
2.2　方法
2.2.1　问卷调查
由统一培训合格的调查员同研究对象以面对面方式进行问卷调查。问卷内容包括年龄、性别、职业、文化程度、吸烟、饮酒、既往病史、食盐摄入情况等。其中，年龄按照1982年联合国提出的分段法进行划分：15~59岁被认定为成年人口，60岁及以上则被认定为老年人口[14]。文职人员指在党政机关及企事业单位的从业者，技术人员指从事教育、医疗、法律、科技或科研等领域的从业者。吸烟指每天吸一支以上并连续或累计6个月以上者。饮酒指每周饮用含酒精的饮料1次以上并连续或累计6个月以上者。
2.2.2　体格检查
由经过统一培训的调查人员对调查对象进行身高、体重和血压的测量，并计算BMI，BMI=体重（kg）/身高（m）2。
2.2.3　甲状腺超声检查
由专业超声科医师对研究对象的甲状腺进行全面检测，按照《甲状腺结节超声诊断规范》进行甲状腺结节诊断，B超显示甲状腺有一个或多个结节患者则判定为甲状腺结节[15]。
2.2.4　实验室检测
采集调查对象清晨空腹静脉血5 mL，按照操作标准冷链保存并送至实验室检测，每批样本检测前均严格进行实验室质控工作。采用Maglumi2000全自动化学发光测定仪（深圳市新产业生物医学工程股份有限公司）测定HbA1c、碱性磷酸酶等生化指标。
2.3　统计学方法
应用SPSS 26.0对数据进行统计分析。计量资料中符合正态分布的以x±s表示，组间比较使用t检验；不符合正态分布的以中位数和四分位间距表示，组间比较使用秩和检验。计数资料采用频数（百分比）进行统计描述，组间差异采用χ2检验进行分析。采用logistic回归分析甲状腺结节的影响因素；采用Spearman秩相关分析探究BMI与HbA1c的相关性；采用bootstrap方法分析HbA1c是否介导了BMI和甲状腺结节之间的关联。检验水准α=0.05。
3　结果
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3.1　研究对象的基本信息
参与本研究的调查人群共1 627人，成年人（<60岁）占95.2%，老年人（≥60岁）占4.8%。其中男性520人，女性1 107人，男女比例约为1：2。总人群中检出甲状腺结节患者共计666人，甲状腺结节检出率为40.9%，其中男性199人，女性467人，分别占甲状腺结节检出人数的29.9%和70.1%。
根据是否检出结节将调查人群分为结节组与非结节组，结节组和非结节组的BMI分别为 22.86 (20.81, 25.33) kg/ m2和22.52 (20.45, 25.16) kg/ m2，结节组BMI显著高于非结节组（P<0.05）。此外，两组间的年龄、职业、文化程度、食盐摄入情况差异均有统计学意义（P<0.05），而性别、吸烟及饮酒情况差异均无统计学意义（P>0.05）。在生化指标方面，结节组与非结节组的HbA1c水平、碱性磷酸酶水平差异均有统计学意义（P<0.05），结节组HbA1c水平 5.4 (5.2, 5.7)%显著高于非结节组5.3(5.1, 5.5)%，结节组碱性磷酸酶水平 65 (54, 79) U/L显著高于非结节组 61 (50, 74) U/L。结果见表1。
3.2　甲状腺结节影响因素的单因素logistic回归分析
单因素logistic回归分析结果显示，老年人（≥60岁）、BMI升高、仅摄入非加碘盐、HbA1c水平升高及碱性磷酸酶水平升高是发生甲状腺结节的危险因素，而职业为文职人员和技术人员者发生甲状腺结节风险降低，OR（95% CI）分别为0.702（0.532~0.925）和0.651（0.505~0.840），P<0.05。文化程度在研究生及以上水平者发生甲状腺结节的风险降低, OR（95% CI）为0.449（0.272~0.741），P<0.05。结果见图1。
3.3　BMI与甲状腺结节患病关系的多因素logistic回归分析
多因素logistic回归分析采用三种模型进一步探讨BMI对甲状腺结节的影响。结果显示无论是否进行模型校正，BMI水平升高均是甲状腺结节患病的危险因素（P<0.05）。其中，调整了年龄、性别、职业、文化程度、食盐摄入情况、吸烟、饮酒、碱性磷酸酶水平等混杂因素后，BMI水平每增加一个单位，甲状腺结节的患病风险升高1.038倍（P<0.05）。结果见表2。
3.4　HbA1c与甲状腺结节患病关系的多因素logistic回归分析
多因素logistic回归分析以HbA1c水平为自变量，是否患有甲状腺结节为因变量，采用三种模型进一步探讨HbA1c对甲状腺结节的影响。结果显示无论是否进行模型校正，HbA1c水平升高均是甲状腺结节患病的危险因素（P<0.05）。其中，调整了年龄、性别、职业、文化程度、食盐摄入情况、吸烟、饮酒、碱性磷酸酶水平等混杂因素后，HbA1c水平每增加一个单位，甲状腺结节的患病风险升高1.297倍（P<0.05）。结果见表3。
3.5　HbA1c在BMI和甲状腺结节关联的中介效应分析
本研究发现，HbA1c水平和BMI水平升高均为甲状腺结节患病的危险因素，Spearman秩相关分析结果显示BMI与HbA1c水平呈正相关（ρ=0.36，P< 0.001）。采用bootstrap法进一步分析HbA1c在BMI和甲状腺结节关联间的中介效应。结果表明BMI对甲状腺结节的患病的直接效应为[β=0.039，95% CI（0.004~0.074）]，并且HbA1c部分介导了BMI 对甲状腺结节患病的影响[β=0.018，95% CI（0.007~0.035）]，总效应值为β=0.057，中介效应的效应量占总效应的31.58%，结果见图2。
4　讨论
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本研究共调查了1 627名体检人员，人群中甲状腺结节的检出率为40.9%。与Li等人在我国30个省市和地区的研究相比，本研究的甲状腺结节检出率高于全国甲状腺结节平均检出率（36.9%），低于吉林（47.6%）、辽宁（44.8%）和山东（43.9%），而与北京（39.3%）、天津（39.4%）相近[16]。不同地区的患病率存在差异可能是由遗传、环境因素和生活方式等多种原因造成。该结果与本课题组既往研究相比，本研究的甲状腺结节检出率高于深圳市2018年社区居民甲状腺结节检出率（34.2%），与全国甲状腺结节检出率年均升高1.92%的趋势相一致[17]。本研究发现老年人、BMI升高、仅摄入非加碘盐、HbA1c水平升高及碱性磷酸酶水平升高与甲状腺结节患病呈正相关，即使在控制混杂因素后，BMI和HbA1c水平升高仍为甲状腺结节的危险因素，这与多项研究结果相符[9,18]。
已有研究发现，BMI可通过代谢异常、脂肪因子、炎症因子等多因素导致甲状腺结节的发生[19-21]。Engin与Manole等人的研究表明，甲状腺结节的发生与体内脂肪蓄积导致的激素水平改变密切相关，脂肪组织会通过促炎细胞因子的过度表达、胰岛素抵抗、胰岛素样生长因子途径的过度激活和过度氧化应激等多种方式致使雌激素水平升高，雌激素又会进一步增加细胞周期蛋白D1表达、c-myc/c-fos通路、丝裂原活化蛋白激酶（Mitogen-Activated Protein Kinase, MAPK）细胞质信号传导刺激等多种途径促进人甲状腺肿瘤细胞生长，在甲状腺结节发生和发展中发挥重要作用[19-20]。Vondra与Sanchez等人的研究则表明，肥胖与甲状腺结节的关系可能与脂肪组织分泌的瘦素有关，肥胖人群中血清瘦素浓度的增加可通过激活促甲状腺激素释放激素（Thyrotropin-Releasing Hormone, TRH）基因转录和刺激激素原转化酶1（Prohormone Convertase 1, PC1）和激素原转化酶2（Prohormone Convertase 2, PC2）表达来增加TRH的合成，继而促进体内促甲状腺激素（Thyroid-Stimulating Hormone, TSH）水平的上升，促进甲状腺结节的发生[21-22]。综上所述，BMI升高引发的激素水平变化、糖脂代谢紊乱以及促炎细胞因子和瘦素的增加均与甲状腺结节密切相关，即BMI及其引起的代谢异常在甲状腺结节的发生和发展中起着关键作用。
HbA1c是红细胞中血红蛋白与血糖的结合体，其与血糖水平呈正相关，它可以稳定地反映人体过去90~120天的平均血糖水平，是反应人体糖代谢水平的重要指标[23]。Chang等人的一项研究表明，HbA1c水平升高与甲状腺结节的发生密切相关，甲状腺结节组的HbA1c水平显著高于非甲状腺结节组[18]。目前尚没有直接明确的证据表明HbA1c与甲状腺结节之间存在直接的因果关系，但Eggo与Tirosh等人的研究发现，高血糖状态可导致的胰岛素抵抗可通过胰岛素或胰岛素样生长因子-1直接激活增殖通路，同时改变甲状腺血管结构，从而促进甲状腺结节的形成[24-25]。此外，高血糖状态还可能影响机体的免疫状态，导致甲状腺组织的慢性炎症，进而促进甲状腺结节的形成[26]。
鉴于BMI和HbA1c在甲状腺结节发生机制中的显著作用和它们之间的相互作用，本研究进一步分析了中介效应。结果显示HbA1c部分介导了BMI与甲状腺结节之间的关联，中介效应的效应量占总效应的31.58%，即BMI升高与甲状腺结节患病显著相关，并会通过HbA1c水平升高增加甲状腺结节的患病风险，这可能是由于BMI升高不仅会引起激素水平升高和胰岛素抵抗，还会导致糖脂代谢紊乱（如HbA1c水平升高），诸多因素共同作用于下游通路，进一步激活c-myc/c-fos通路和MAPK细胞质信号传导等多种途径，最终促进了甲状腺结节的发生。本研究也存在一定的局限性。首先，本研究为横断面研究，因此无法明确因果关系，仅能探讨 BMI、HbA1c 与甲状腺结节之间的关联性，而不能确定其因果方向性。未来需要通过前瞻性研究进一步验证相关结论。其次，尽管我们纳入了1627名研究对象，但样本量依然可能不足以探讨较弱的关联，尤其是对于某些亚组的分析，可能存在统计效力不足的情况，未来更大规模的研究可以进一步增强结论的稳健性。最后，本研究数据来自深圳地区的研究对象，样本具有一定的地域局限性，因此所得结论可能不完全适用于其他地区人群，未来的研究需要在不同地区进行验证，以提高结论的普遍适用性。总之，本研究发现BMI、HbA1c水平升高均是甲状腺结节患病的危险因素，且HbA1c部分介导了BMI对甲状腺结节患病的影响。因此，综合管理BMI和血糖水平，加强宣传教育，倡导健康的生活方式，对于有效降低甲状腺结节的患病风险，提升人群整体健康水平十分重要和必要。
基金
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  • 国家自然科学基金面上项目(22176132)
  • 深圳市科创委面上项目(JCYJ20210324135000001)
  • 广东省医学科研基金(20221119115615564)
  • 深圳市医科院项目(B2403008)
文献
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参考文献 引证文献
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2025年第52卷第4期
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doi: 10.20043/j.cnki.MPM.202407403
  • 接收时间：2024-07-22
  • 首发时间：2026-03-18
  • 出版时间：2025-02-25
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  • 收稿日期：2024-07-22
基金
国家自然科学基金面上项目(22176132)
深圳市科创委面上项目(JCYJ20210324135000001)
广东省医学科研基金(20221119115615564)
深圳市医科院项目(B2403008)
作者信息
    1.山西医科大学医学科学院，山西 太原 030001
    2.南方科技大学公共卫生及应急管理学院
    3.深圳市疾病预防控制中心

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张建清与宋嘉宜为共同通信作者。张建清，E-mail：；
宋嘉宜，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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