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Article(id=1241035817112629991, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202407544, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1722009600000, receivedDateStr=2024-07-27, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773815596130, onlineDateStr=2026-03-18, pubDate=1733760000000, pubDateStr=2024-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773815596130, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773815596130, creator=13701087609, updateTime=1773815596130, updator=13701087609, issue=Issue{id=1241035810628235909, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='23', pageStart='4225', pageEnd='4416', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773815594584, creator=13701087609, updateTime=1773815743629, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241036435843764756, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241036435843764757, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241035810628235909, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=4225, endPage=4230, ext={EN=ArticleExt(id=1241035819310445310, articleId=1241035817112629991, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Relationship between the glycated albumin to glycated hemoglobin ratio and all-cause mortality in patients with metabolic syndrome, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To analyze the relationship between the ratio of glycated albumin to glycated hemoglobin (GA/HbA1c)and all-cause mortality in adults with metabolic syndrome MetS.

Methods

This study is a retrospective cohort study utilizing data from the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) from 1999 to 2004. A total of 1 497 eligible participants were included and followed up until December 31, 2019. The relationship between the GA/HbA1c ratio and all-cause mortality in MetS patients was assessed using Kaplan-Meier survival curves, multivariable weighted Cox regression, and restricted cubic splines.

Results

Among a weighted population of 55 224 898 eligible individuals with a median follow-up of 16.3 years, there were 501 cases of all-cause mortality. Participants were divided into three groups(T1, T2, T3) based on weighted tertiles of the GA/HbA1c ratio. After adjusting for covariates, a higher GA/HbA1c ratio (T3) was associated with an increased risk of all-cause mortality in MetS patients compared to the lowest tertile (T1) (HR=1.335, 95%CI:1.010-1.772). The restricted cubic spline analysis also revealed a non-linear “S” shaped relationship between the GA/HbA1c ratio and all-cause mortality (non-linear P<0.05). Subgroup analyses (all interaction P>0.05) and sensitivity analyses (HR=1.344, 95%CI: 1.014-1.783) showed similar results.

Conclusion

There is a non-linear association between the GA/HbA1c ratio and all-cause mortality in patients with metabolic syndrome, with higher GA/HbA1c ratios linked to an increased risk of all-cause mortality in these patients.

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目的

分析成人代谢综合征(metabolic syndrome, MetS)患者糖化白蛋白及糖化血红蛋白(GA/HbA1c)比值与全因死亡率之间的关系。

方法

本研究为回顾性队列研究，选用美国国家健康和营养调查(NHANES)和美国国家死亡索引(NDI)1999—2004年数据库。共纳入1 497例符合条件的参与者，随访至2019年12月31日。使用Kaplan-Meier生存曲线、多因素加权Cox回归和限制性立方样条分析评估MetS患者GA/HbA1c比值和全因死亡率之间的关系。

结果

在中位随访16.3年期间，55 224 898例符合纳入标准的加权人群共发生501例全因死亡。按GA/HbA1c比值加权三分位数将参与者分为T1、T2和T3三组，在校正协变量后，与最低三分位数(T1)相比，较高的GA/HbA1c比值(T3)与MetS患者的全因死亡风险升高(HR=1.335，95%CI:1.010～1.772)有关。限制性立方样条分析还揭示了GA/HbA1c比值与全因死亡率之间的“S”形关系(非线性P<0.05)。亚组分析(所有交互作用P>0.05)和敏感性分析(HR=1.344，95%CI:1.014～1.783)也呈现相似的结果。

结论

MetS患者的GA/HbA1c比值与全因死亡率之间存在非线性相关性，较高的GA/HbA1c比值与MetS患者全因死亡风险增加有关。

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刘早玲，E-mail:
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刘早玲（1972—），女，博士，教授，研究方向：统计学在现代医学中的应用

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Oxidative Medicine and Cellular Longevity, 2019, 2019: 9570616., articleTitle=Advanced glycation end products: potential mechanism and therapeutic target in cardiovascular complications under diabetes, refAbstract=null)], funds=[Fund(id=1241069117357224272, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, awardId=82160605, language=CN, fundingSource=国家自然科学基金项目(82160605), fundOrder=null, country=null), Fund(id=1241069117445304662, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, awardId=null, language=CN, fundingSource=新疆维吾尔自治区“十四五”高等学校特色学科-公共卫生与预防医学, fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241069111896240186, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, xref=null, ext=[AuthorCompanyExt(id=1241069111904628795, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, companyId=1241069111896240186, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830000, China), AuthorCompanyExt(id=1241069111908823101, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, companyId=1241069111896240186, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=新疆医科大学公共卫生学院，新疆 乌鲁木齐 830000)])], figs=[ArticleFig(id=1241069115599810761, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Figure 1, caption=Flow chart of patients enrollment, figureFileSmall=ezt+rgsmpPfCLrMFcb/OWw==, figureFileBig=gHrRA1WvP2lIXx6Qg/kGfw==, tableContent=null), ArticleFig(id=1241069115679502546, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=图1, caption=入组患者流程图, figureFileSmall=ezt+rgsmpPfCLrMFcb/OWw==, figureFileBig=gHrRA1WvP2lIXx6Qg/kGfw==, tableContent=null), ArticleFig(id=1241069115792748764, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Figure 2, caption=Restricted cubic spline model for the associations between GA/HbA1c ratio and all-cause mortality, figureFileSmall=wO8l/AHJfF17q8AffpkKTw==, figureFileBig=dBgb2gptfMm9b4rvzHRDDg==, tableContent=null), ArticleFig(id=1241069115905994985, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=图2, caption=GA/HbA1c比值与全因死亡率的限制立方样条图, figureFileSmall=wO8l/AHJfF17q8AffpkKTw==, figureFileBig=dBgb2gptfMm9b4rvzHRDDg==, tableContent=null), ArticleFig(id=1241069116010852598, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Figure 3, caption=Forest plot for subgroup analysis of association between the GA/HbA1c ratio and all-cause mortality, figureFileSmall=+yB3k4SbR0agq0A6wxlnUA==, figureFileBig=+dCb5WG+0bbxFLxMnERyxw==, tableContent=null), ArticleFig(id=1241069116111515904, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=图3, caption=亚组分析GA/HbA1c比值与全因死亡率之间的关系, figureFileSmall=+yB3k4SbR0agq0A6wxlnUA==, figureFileBig=+dCb5WG+0bbxFLxMnERyxw==, tableContent=null), ArticleFig(id=1241069116266705161, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Table 1, caption=

Baseline characteristics of patients with MetS grouped according to weighted tertiles of the GA/HbA1c ratio in NHANES, 1999—2004 ［，n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总计(n=1 497)GA/HbA1c比值加权三分位数分组F/H/χ2值P值
T1(n=366)T2(n=504)T3(n=627)
加权人数55 224 898±18 482 391±18 334 558±18 407 949±
年龄(岁)49.5315.84±43.9115.25±49.2614.63±55.4515.50±135.74<0.001
BMI(kg/m2)33.367.2537.277.6632.856.7329.945.18229.32<0.001
性别5.4610.007
男性696(50.64)195(58.72)225(45.71)276(47.43)
女性801(49.36)171(41.28)279(54.29)351(52.57)
种族2.4400.033
墨西哥裔417(7.65)129(9.15)123(6.79)165(7.00)
其他西班牙裔59(5.08)19(6.54)15(2.91)25(5.77)
非西班牙裔白人791(76.07)178(77.10)290(78.57)323(72.54)
非西班牙裔黑人190(7.44)36(5.80)61(7.01)93(9.50)
其他40(3.76)4(1.40)15(4.71)21(5.19)
教育程度2.2270.085
高中以下541(22.70)149(25.95)151(16.15)241(25.94)
高中及同等学历373(29.20)88(29.57)134(30.81)151(27.24)
大学及以上583(48.10)129(44.48)219(53.04)235(46.82)
婚姻状况3.8840.007
未婚152(12.41)47(16.10)58(12.93)47(8.19)
已婚或同居970(67.24)240(68.64)327(66.35)403(66.73)
离婚、丧偶或分居375(20.34)79(15.26)119(20.72)177(25.07)
家庭收入1.6360.182
低265(12.30)70(11.25)86(11.36)109(14.27)
中636(36.70)162(39.49)189(32.71)285(37.89)
高596(51.00)134(49.26)229(55.93)233(47.84)
吸烟状况0.9690.413
从不吸烟763(51.74)191(54.59)240(48.12)332(52.47)
戒烟458(27.70)106(26.19)149(27.57)203(29.36)
吸烟276(20.56)69(19.22)115(24.31)92(18.17)
是否饮酒2.5100.088
是934(66.43)125(71.06)327(65.52)366(62.68)
否563(33.57)241(28.94)177(34.48)261(37.32)
是否患癌10.319<0.001
是145(8.45)21(4.28)39(7.61)85(13.46)
否1 352(91.55)345(95.72)465(92.39)542(86.54)
腹部肥胖128.696<0.001
是1 129(67.43)160(29.16)448(90.49)521(82.89)
否368(32.57)206(70.84)56(9.51)106(17.11)
血压异常46.253<0.001
是1 038(68.97)302(87.26)290(54.05)446(65.48)
否459(31.03)64(12.74)214(45.95)181(34.52)
血糖异常42.240<0.001
是535(28.11)66(10.89)190(33.75)279(39.77)
否962(71.89)300(89.11）314(66.25)348(60.23)
TG异常30.107<0.001
是1 097(77.49)322(91.86)355(71.95)420(68.59)
否400(22.51)44(8.14)149(28.05)207(31.41)
HDL异常53.994<0.001
是1 300(89.76)351(98.15)439(89.86)510(81.24)
否197(10.24)15(1.85)65(10.14)117(18.76)
全因死亡501(24.25)93(18.08)136(20.89)272(33.80)13.774<0.001
), ArticleFig(id=1241069116417700124, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=表1, caption=

NHANES 1999—2004年GA/HbA1c比值的加权三分位数分组的MetS患者基线特征［，n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
指标总计(n=1 497)GA/HbA1c比值加权三分位数分组F/H/χ2值P值
T1(n=366)T2(n=504)T3(n=627)
加权人数55 224 898±18 482 391±18 334 558±18 407 949±
年龄(岁)49.5315.84±43.9115.25±49.2614.63±55.4515.50±135.74<0.001
BMI(kg/m2)33.367.2537.277.6632.856.7329.945.18229.32<0.001
性别5.4610.007
男性696(50.64)195(58.72)225(45.71)276(47.43)
女性801(49.36)171(41.28)279(54.29)351(52.57)
种族2.4400.033
墨西哥裔417(7.65)129(9.15)123(6.79)165(7.00)
其他西班牙裔59(5.08)19(6.54)15(2.91)25(5.77)
非西班牙裔白人791(76.07)178(77.10)290(78.57)323(72.54)
非西班牙裔黑人190(7.44)36(5.80)61(7.01)93(9.50)
其他40(3.76)4(1.40)15(4.71)21(5.19)
教育程度2.2270.085
高中以下541(22.70)149(25.95)151(16.15)241(25.94)
高中及同等学历373(29.20)88(29.57)134(30.81)151(27.24)
大学及以上583(48.10)129(44.48)219(53.04)235(46.82)
婚姻状况3.8840.007
未婚152(12.41)47(16.10)58(12.93)47(8.19)
已婚或同居970(67.24)240(68.64)327(66.35)403(66.73)
离婚、丧偶或分居375(20.34)79(15.26)119(20.72)177(25.07)
家庭收入1.6360.182
低265(12.30)70(11.25)86(11.36)109(14.27)
中636(36.70)162(39.49)189(32.71)285(37.89)
高596(51.00)134(49.26)229(55.93)233(47.84)
吸烟状况0.9690.413
从不吸烟763(51.74)191(54.59)240(48.12)332(52.47)
戒烟458(27.70)106(26.19)149(27.57)203(29.36)
吸烟276(20.56)69(19.22)115(24.31)92(18.17)
是否饮酒2.5100.088
是934(66.43)125(71.06)327(65.52)366(62.68)
否563(33.57)241(28.94)177(34.48)261(37.32)
是否患癌10.319<0.001
是145(8.45)21(4.28)39(7.61)85(13.46)
否1 352(91.55)345(95.72)465(92.39)542(86.54)
腹部肥胖128.696<0.001
是1 129(67.43)160(29.16)448(90.49)521(82.89)
否368(32.57)206(70.84)56(9.51)106(17.11)
血压异常46.253<0.001
是1 038(68.97)302(87.26)290(54.05)446(65.48)
否459(31.03)64(12.74)214(45.95)181(34.52)
血糖异常42.240<0.001
是535(28.11)66(10.89)190(33.75)279(39.77)
否962(71.89)300(89.11）314(66.25)348(60.23)
TG异常30.107<0.001
是1 097(77.49)322(91.86)355(71.95)420(68.59)
否400(22.51)44(8.14)149(28.05)207(31.41)
HDL异常53.994<0.001
是1 300(89.76)351(98.15)439(89.86)510(81.24)
否197(10.24)15(1.85)65(10.14)117(18.76)
全因死亡501(24.25)93(18.08)136(20.89)272(33.80)13.774<0.001
), ArticleFig(id=1241069116572889383, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Table 2, caption=

Association of GA/HbA1c ratio with all-cause mortality

, figureFileSmall=null, figureFileBig=null, tableContent=
GA/HbA1c比值模型1P值模型2P值模型3P值
HR (95%CI)HR (95%CI)HR (95%CI)
GA/HbA1c比值(连续变量)1.276(1.118～1.456)<0.0011.146(0.984～1.335)0.0791.082(0.931～1.257)0.300
GA/HbA1c比值(分类变量)
T1参照参照参照
T21.383(1.012～1.888)0.0411.052(0.791～1.397)0.7290.996(0.741～1.339)0.978
T32.363(1.743～3.203)<0.0011.404(1.061～1.858)0.0181.335(1.010～1.772)0.046
), ArticleFig(id=1241069116824547636, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=表2, caption=

GA/HbA1c比值与全因死亡率的相关性

, figureFileSmall=null, figureFileBig=null, tableContent=
GA/HbA1c比值模型1P值模型2P值模型3P值
HR (95%CI)HR (95%CI)HR (95%CI)
GA/HbA1c比值(连续变量)1.276(1.118～1.456)<0.0011.146(0.984～1.335)0.0791.082(0.931～1.257)0.300
GA/HbA1c比值(分类变量)
T1参照参照参照
T21.383(1.012～1.888)0.0411.052(0.791～1.397)0.7290.996(0.741～1.339)0.978
T32.363(1.743～3.203)<0.0011.404(1.061～1.858)0.0181.335(1.010～1.772)0.046
), ArticleFig(id=1241069116983931197, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=EN, label=Table 3, caption=

Association between GA/HbA1c ratio and all-cause mortality after exclusion of MetS patients who died during the first year of follow-up

, figureFileSmall=null, figureFileBig=null, tableContent=
GA/HbA1c比值模型1P值模型2P值模型3P值
HR (95%CI)HR (95%CI)HR (95%CI)
GA/HbA1c比值(连续变量)1.275(1.117～1.445)<0.0011.141(0.978～1.333)0.0941.076(0.924～1.254)0.346
GA/HbA1c比值 (分类变量)
T1参照参照参照
T21.396(1.025～1.902)0.0341.057(0.798～1.401)0.6980.999(0.743～1.342)0.993
T32.397(1.769～3.248)<0.0011.418(1.074～1.872)0.0141.344(1.014～1.783)0.040
), ArticleFig(id=1241069117122343233, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241035817112629991, language=CN, label=表3, caption=

排除随访第一年内死亡受试者后GA/HbA1c比值与全因死亡率的关系

, figureFileSmall=null, figureFileBig=null, tableContent=
GA/HbA1c比值模型1P值模型2P值模型3P值
HR (95%CI)HR (95%CI)HR (95%CI)
GA/HbA1c比值(连续变量)1.275(1.117～1.445)<0.0011.141(0.978～1.333)0.0941.076(0.924～1.254)0.346
GA/HbA1c比值 (分类变量)
T1参照参照参照
T21.396(1.025～1.902)0.0341.057(0.798～1.401)0.6980.999(0.743～1.342)0.993
T32.397(1.769～3.248)<0.0011.418(1.074～1.872)0.0141.344(1.014～1.783)0.040
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代谢综合征患者糖化白蛋白及糖化血红蛋白比值与全因死亡率的关系
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刘早玲 , 唐溢乐 , 苏津 , 杨紫森
现代预防医学 | 流行病与统计方法 2024,51(23): 4225-4230
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现代预防医学 | 流行病与统计方法 2024, 51(23): 4225-4230
代谢综合征患者糖化白蛋白及糖化血红蛋白比值与全因死亡率的关系
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刘早玲 , 唐溢乐, 苏津, 杨紫森
作者信息
  • 新疆医科大学公共卫生学院，新疆 乌鲁木齐 830000

    • 刘早玲（1972—），女，博士，教授，研究方向：统计学在现代医学中的应用

通讯作者:

刘早玲，E-mail:
Relationship between the glycated albumin to glycated hemoglobin ratio and all-cause mortality in patients with metabolic syndrome
Zao-ling LIU , Yi-le TANG, Jin SU, Zi-sen YANG
Affiliations
  • School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830000, China
出版时间: 2024-12-10 doi: 10.20043/j.cnki.MPM.202407544
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摘要
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目的

分析成人代谢综合征(metabolic syndrome, MetS)患者糖化白蛋白及糖化血红蛋白(GA/HbA1c)比值与全因死亡率之间的关系。

方法

本研究为回顾性队列研究，选用美国国家健康和营养调查(NHANES)和美国国家死亡索引(NDI)1999—2004年数据库。共纳入1 497例符合条件的参与者，随访至2019年12月31日。使用Kaplan-Meier生存曲线、多因素加权Cox回归和限制性立方样条分析评估MetS患者GA/HbA1c比值和全因死亡率之间的关系。

结果

在中位随访16.3年期间，55 224 898例符合纳入标准的加权人群共发生501例全因死亡。按GA/HbA1c比值加权三分位数将参与者分为T1、T2和T3三组，在校正协变量后，与最低三分位数(T1)相比，较高的GA/HbA1c比值(T3)与MetS患者的全因死亡风险升高(HR=1.335，95%CI:1.010～1.772)有关。限制性立方样条分析还揭示了GA/HbA1c比值与全因死亡率之间的“S”形关系(非线性P<0.05)。亚组分析(所有交互作用P>0.05)和敏感性分析(HR=1.344，95%CI:1.014～1.783)也呈现相似的结果。

结论

MetS患者的GA/HbA1c比值与全因死亡率之间存在非线性相关性，较高的GA/HbA1c比值与MetS患者全因死亡风险增加有关。

代谢综合征  /  糖化白蛋白  /  糖化血红蛋白  /  全因死亡率  /  NHANES
Objective

To analyze the relationship between the ratio of glycated albumin to glycated hemoglobin (GA/HbA1c)and all-cause mortality in adults with metabolic syndrome MetS.

Methods

This study is a retrospective cohort study utilizing data from the National Health and Nutrition Examination Survey (NHANES) and the National Death Index (NDI) from 1999 to 2004. A total of 1 497 eligible participants were included and followed up until December 31, 2019. The relationship between the GA/HbA1c ratio and all-cause mortality in MetS patients was assessed using Kaplan-Meier survival curves, multivariable weighted Cox regression, and restricted cubic splines.

Results

Among a weighted population of 55 224 898 eligible individuals with a median follow-up of 16.3 years, there were 501 cases of all-cause mortality. Participants were divided into three groups(T1, T2, T3) based on weighted tertiles of the GA/HbA1c ratio. After adjusting for covariates, a higher GA/HbA1c ratio (T3) was associated with an increased risk of all-cause mortality in MetS patients compared to the lowest tertile (T1) (HR=1.335, 95%CI:1.010-1.772). The restricted cubic spline analysis also revealed a non-linear “S” shaped relationship between the GA/HbA1c ratio and all-cause mortality (non-linear P<0.05). Subgroup analyses (all interaction P>0.05) and sensitivity analyses (HR=1.344, 95%CI: 1.014-1.783) showed similar results.

Conclusion

There is a non-linear association between the GA/HbA1c ratio and all-cause mortality in patients with metabolic syndrome, with higher GA/HbA1c ratios linked to an increased risk of all-cause mortality in these patients.

Metabolic syndrome  /  Glycated albumin  /  Glycated hemoglobin  /  All-cause mortality  /  NHANES
刘早玲, 唐溢乐, 苏津, 杨紫森. 代谢综合征患者糖化白蛋白及糖化血红蛋白比值与全因死亡率的关系. 现代预防医学, 2024 , 51 (23) : 4225 -4230 . DOI: 10.20043/j.cnki.MPM.202407544
Zao-ling LIU, Yi-le TANG, Jin SU, Zi-sen YANG. Relationship between the glycated albumin to glycated hemoglobin ratio and all-cause mortality in patients with metabolic syndrome[J]. Modern Preventive Medicine, 2024 , 51 (23) : 4225 -4230 . DOI: 10.20043/j.cnki.MPM.202407544
正文
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代谢综合征(metabolic syndrome, MetS)是以中心性肥胖、胰岛素抵抗(insulin resistance, IR)、高血压、高甘油三酯(triglyceride, TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)降低和葡萄糖耐量降低或2型糖尿病为临床特征的一系列代谢紊乱综合征[1-2]。在亚洲、欧洲、墨西哥和美国的部分地区，MetS的患病率从24.3%到44.2%不等[3]。MetS与糖尿病、心脑血管疾病等临床疾病密切相关，MetS患者是发生心脑血管疾病的高危人群，与非MetS患者相比其罹患心血管疾病和糖尿病的风险分别增加2倍和5倍[4]。近年来，有研究指出糖化白蛋白(glycated albumin, GA)及糖化血红蛋白(hemoglobin A1c, HbA1c)的比值(GA/HbA1c)可以作为衡量糖尿病患者血糖波动的有效指标[5]。既往研究表明，较高的GA/HbA1c比值可能与糖尿病患者并发症风险升高有关，如外周动脉疾病[6]、肾脏疾病[7]等。最新研究还观察到GA/HbA1c比值升高与美国成人[8]和患有非酒精性脂肪性肝病[9](nonalcoholic fatty liver disease, NAFLD)的美国成人全因死亡风险增加有关，然而MetS患者GA/HbA1c比值与长期预后关系目前仍缺少研究。本研究使用1999—2004年全国健康与营养调查(NHANES)的数据，分析美国成人MetS患者全因死亡率与GA/HbA1c比值水平之间的关系，探讨代谢综合征患者死亡预测的有效指标。
1 资料与方法
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1.1 研究对象
NHANES是美国国家卫生统计中心(NCHS)的全国代表性项目，旨在评估美国普通人群的健康状况。NHANES通过复杂的统计过程，采用分层、多阶段的概率抽样来反映常住人口信息[10]。NCHS伦理审查委员会批准了NHANES的研究，并获得了每位参与者的书面知情同意书。
因为NHANES仅在1999—2004年测量了GA，故本研究使用了该数据库自1999—2004年共3个测量周期的数据。所有受试者均进行前瞻性随访至2019年12月31日。在三个周期的31 126名受试者中，排除了年龄在20岁以下、缺乏GA、HbA1c和数据资料不完整的参与者。本研究的流程图见图1。
1.2 代谢综合征的诊断标准
关于MetS的诊断标准存在争议，目前全球范围内并没有一个统一的诊断标准，不同地区和国家的诊断标准有所差异。在众多的代谢综合征诊断标准中，NCEP ATPIII-2005标准因其在临床和流行病学研究中的易用性而广受推崇。
NCEP ATPIII-2005标准[11]如下，MetS患者即满足以下标准中的3个或以上的人：（1）腰围升高：男性腰围≥102 cm或女性腰围≥88 cm；（2）血压升高：血压≥130/85 mm Hg或对既往诊断的高血压进行药物治疗；（3）HDL-C降低：男性<40 mg/dl，女性<50 mg/dl或对既往HDL-C降低采取特殊治疗；（4）TG升高：TG水平≥150 mg/dl或针对TG升高进行药物治疗；（5）空腹血糖升高：空腹血糖≥100 mg/dl或既往诊断为2型糖尿病且使用药物治疗血糖升高。
1.3 GA/HbA1c的定义
按照NHANES推荐的方法对收集到的血清标本中的GA[12-13]和HbA1c[14-15]进行测定。GA/HbA1c比值等于GA值除以HbA1c值[8]。
1.4 协变量的纳入
通过标准化问卷收集了参与者的详细人口统计信息，包括年龄、性别、种族、教育水平、婚姻状况和家庭收入等变量。此外，问卷还涵盖了参与者的生活习惯，如吸烟和饮酒行为，以及参与者的既往癌症病史。以下是协变量的详细信息。
种族分为非西班牙裔白人、非西班牙裔黑人、墨西哥裔美国人等5类。教育程度分为高中以下、高中毕业、大学及以上3类。婚姻状况分为已婚或与伴侣同居，从未结婚，丧偶、离婚或分居[16]。家庭收入与联邦贫困线比率(PIR)反映了家庭收入情况，PIR越高表明家庭收入状况越好[10]，家庭收入情况分为低收入(PIR<1)、中收入(1≤PIR≤3)、高收入(PIR>3)[9]。吸烟情况分为从不吸烟、戒烟者和当前吸烟者，从不吸烟者被定义为一生中吸烟少于100支的人，戒烟者被定义为吸过≥100支香烟但在调查时未吸烟的个人，当前吸烟者被定义为已吸过≥100支香烟且在调查时仍在吸烟的个人[17]。将一年中至少喝过12杯酒精饮料的参与者定义为饮酒者[18]。根据美国疾病控制与预防中心(CDC)和世界卫生组织目前的指南，将正常BMI范围定义为18.5～24.9 kg/m2，BMI≥25 kg/m2定义为超重，BMI≥30 kg/m2定义为肥胖[19]。
1.5 死亡结局的确定
本研究中的死亡结局是通过NHANES的相关数据并参照截至2019年12月31日的美国国家死亡索引(National Death Index, NDI)记录来最终确定的。本研究的主要结局是全因死亡，此方法已经在先前研究中被描述并已被广泛接受[20]。研究的随访期从参与者的GA和HbA1c测量日期开始，持续至死亡日期或观测截止日期。
1.6 统计学方法
因为NHANES使用复杂抽样技术来选择美国人口的代表性样本，为了确保研究的可靠性，本研究按照NHANES的分析策略，整合了NHANES研究中创建的空腹样本权重(WTSAF4YR和WTSAF2YR)，新的样本权重由2/3×WTSAF4YR与1/3×WTSAF2YR合并而来。分类变量以频率和加权百分比表示，符合正态分布的计量资料采用表示，不符合正态分布的资料以［M（P25，P75）］表示。根据先前研究[8]按GA/HbA1c比值加权三分位数将参与者分为三组：T1≤2.101、2.101<T2≤2.406、T3>2.406，其中最低三分位数(T1)被设定为参照组，同时该比值也被作为连续变量进行分析。为了减少因协变量数据缺失导致的样本量损失，本研究采用了多重插补方法对协变量进行插补。经Schoenfeld残差法检验GA/HbA1c比值对生存风险的影响满足PH等比例风险假定后，使用多变量加权Cox比例风险回归模型来评估GA/HbA1c比值与全因死亡率的风险比(HR)和95%置信区间(CI)。此外，为了探索GA/HbA1c比值与全因死亡率之间的剂量-反应关系，本研究还进行了包含5个节点的限制性立方样条分析。本研究依据先前研究的分类标准[8]，将受试者按年龄、性别、种族和BMI进行分层，对GA/HbA1c比值与全因死亡率的相关性进行了亚组分析。在此基础上，通过在多变量模型中的乘积交互作用项来进行交互作用分析。此外，本研究还在排除了随访第一年内死亡受试者后进行了敏感性分析，从而减少反向因果的干扰。
考虑到研究的复杂性，使用R软件(4.1.3版)对所有结果进行统计学分析。双侧检验水准α=0.05。
2 结果
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2.1 研究人群的基线特征
研究共纳入1 497名MetS患者，其中50.64%为男性，平均年龄(49.53±15.84)岁，中位随访期为16.3年(196月)。研究对象的基线信息见表1。
2.2 不同GA/HbA1c比值水平与代谢综合征患者全因死亡率比较
随访期间共发生501例全因死亡，该群体的累积死亡率为33.46%。为了深入研究GA/HbA1c比值与全因死亡风险之间的潜在联系，本研究按照GA/HbA1c比值的加权三分位数将其分为三组。结果显示，随着GA/HbA1c比值的升高，GA/HbA1c比值分组间的累积死亡率呈现出递增趋势，分别为25.41%、26.98%和43.38%。相应地，全因死亡的加权百分比也从18.08%、20.89%上升至33.80%。组间比较的结果表明，不同GA/HbA1c比值水平与代谢综合征患者全因死亡风险之间存在显著差异(P<0.001)。
2.3 GA/HbA1c比值与代谢综合征患者全因死亡率的关联
采用多变量加权Cox回归模型，分别在三种不同调整程度的模型下分析GA/HbA1c比值与全因死亡率之间的关联。在未校正潜在的混杂因素时，与T1组相比，T2组(HR=1.383, 95%CI:1.012～1.888)和T3组(HR=2.363, 95%CI:1.743～3.203)的全因死亡率显著增高。在校正年龄、性别和种族后，T2组与T1组相比的全因死亡风险不再显著(HR=1.052, 95%CI:0.791～1.397)，而T3组的全因死亡风险增加40.4%(HR=1.404, 95%CI:1.061～1.858)。在对所有潜在混杂因素进行调整后，与T1组相比，T2组的全因死亡风险仍然没有显著差异(HR=0.996, 95%CI: 0.741～1.339)，T3组的全因死亡风险升高了33.5%(HR= 1.335, 95%CI:1.010～1.772)。
将GA/HbA1c比值作为连续性指标进行分析，在未校正潜在的混杂因素时，GA/HbA1c比值与全因死亡率(HR=1.276, 95%CI:1.118～1.456)的风险增加显著相关。对潜在混杂因素进行调整后，这种关联无统计学意义(HR模型2=1.146, 95%CI:0.984～1.335；HR模型3=1.082, 95%CI: 0.931～1.257)。结果见表2。
2.4 GA/HbA1c比值与MetS患者全因死亡率之间的剂量反应关系
以GA/HbA1c比值为自变量，全因死亡率为因变量，使用限制性立方样条回归模型分析GA/HbA1c比值与全因死亡率之间的非线性关系和拐点。
以AIC最小准则为原则，使用具有5个节点的限制立方样条分析来模拟GA/HbA1c比值与全因死亡之间的关系。如图2所示，在校正了性别、年龄、种族、教育程度等变量后，GA/HbA1c比值与全因死亡之间呈非线性相关(非线性P<0.05)。MetS患者的全因死亡率在GA/HbA1c比值达到2.339时出现一个显著的上升拐点(HR=1.003, 95%CI:1.001～1.005)。当GA/HbA1c比值大于2.339时，GA/HbA1c比值每增加1个单位，全因死亡率增加57.7%(HR=1.580, 95%CI:1.120～2.080)。
2.5 亚组及敏感性分析
如图3所示，本研究进行了亚组分析，结果表明GA/HbA1c比值与全因死亡率在性别、墨西哥裔、非西班牙裔白人、非西班牙裔黑人和肥胖的参与者存在正相关的统计学意义(P<0.05)。交互作用分析结果显示，年龄、性别、种族和BMI与GA/HbA1c比值没有相乘模式下的交互作用(所有交互作用P>0.05)。在排除了随访第一年内死亡受试者后，敏感性分析仍然得到了相似的结果，这进一步加强了结果的稳健性，结果见表3。
3 讨论
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在全国代表性样本的人群队列中，本研究初步观察到GA/HbA1c比值与成年MetS患者的全因死亡风险呈正相关。上述结果在亚组分析和敏感性分析中保持一致，确保了结果的稳健性。然而，当进一步调整了潜在的混杂因素后，研究者注意到T2组与全因死亡率之间的关系不再显著，而T3组则持续表现出与全因死亡风险显著相关的正向关联。此外，将GA/HbA1c比值作为连续变量纳入模型时，其与全因死亡的关联也无统计学意义。这些不一致的结果可能表明GA/HbA1c比值与代谢综合征患者的全因死亡风险之间的关系较为复杂，可能存在非线性关系。为了阐释这种复杂的关系，本研究采用了限制立方样条分析，结果表明GA/HbA1c比值与全因死亡风险之间存在“S”形的非线性曲线关系。值得注意的是，尽管目前还没有关于GA/HbA1c比值与MetS患者全因死亡率之间关系的纵向队列研究的报道，但已有研究表明GA/HbA1c比值的升高与美国成人[8]和NAFLD患者[9]的全因死亡风险增加有关。
先前研究已证实GA水平和HbA1c值升高会增加全因死亡的风险[21-22]。可能的机制如下：首先，白蛋白是血浆中的一种主要药物结合蛋白，显著影响药物的吸收、分布、代谢和疗效[23]。然而，白蛋白的糖化作用会改变其结构和结合效率，从而改变了药效[24]。白蛋白的糖化过程可能导致其过度修饰，这在某些情况下会增加游离药物的浓度，引发严重的药物毒性[25]。其次，白蛋白的糖化速率大约是血红蛋白的10倍，使得它对血糖水平的变化极为敏感[26]，导致GA水平增加。此外，血糖波动会增加氧化应激并导致红细胞寿命缩短[27-28]，进而降低HbA1c水平，两者作用下最终导致GA/HbA1c比值上升。GA可以刺激血小板活化和聚集[29]，从而增强血栓形成并抑制细胞对葡萄糖的摄取[30]，进一步加剧血糖波动。最后，GA还是晚期糖基化终产物(AGEs)的前体物质[6]，AGEs能够激活炎症信号，增加氧化应激，并通过损伤动脉内皮细胞和促进脂质沉积，加速动脉粥样硬化的进程[31]。
本研究具有一些优势和局限性。首先，研究采用了NHANES的全国性多阶段复杂抽样方案，确保了样本的代表性。其次，本研究对多个协变量进行了综合调整，并通过分层分析和敏感性分析，增强了研究结果的稳健性。当然，研究也存在一些局限性。首先，由于NHANES数据库主要基于横断面研究的数据，这种观察性研究设计限制了对因果关系的推断，虽然能够观察到代谢综合征患者的GA/HbA1c比值与全因死亡率之间的“S”形关联，但无法确定二者之间是否存在因果关系。其次，MetS的诊断标准尚未完全统一，不同诊断标准可能导致纳入研究的人群存在差异，这可能对分析结果产生一定的影响。最后，尽管已经尽可能地调整了已知的潜在影响因素，但仍有可能存在未被识别或未被控制的混杂因素，这些因素可能会对研究结果造成一定的偏倚。
综上所述，在具有全国代表性的美国成年人群体中，GA/HbA1c比值与全因死亡率之间存在“S”形的非线性关系，较高的GA/HbA1c比值与成年MetS患者的全因死亡率升高之间呈正相关。本研究的结果提示，GA/HbA1c比值可能成为识别代谢综合症患者死亡风险的有效生物标志物，以帮助可以从早期预防性治疗中获益的高危个体。
基金
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  • 国家自然科学基金项目(82160605)
  • 新疆维吾尔自治区“十四五”高等学校特色学科-公共卫生与预防医学
文献
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参考文献 引证文献
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[1]
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2024年第51卷第23期
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doi: 10.20043/j.cnki.MPM.202407544
  • 接收时间：2024-07-27
  • 首发时间：2026-03-18
  • 出版时间：2024-12-10
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  • 收稿日期：2024-07-27
基金
国家自然科学基金项目(82160605)
新疆维吾尔自治区“十四五”高等学校特色学科-公共卫生与预防医学
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    新疆医科大学公共卫生学院，新疆 乌鲁木齐 830000

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刘早玲，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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