CAJ | 학술논문

目的探讨炎性细胞因子——肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)及脂肪细胞因子——脂联素、瘦素水平与妊娠期糖尿病(GDM)发病的相关性及4种细胞因子水平在产褥期的变化.方法 2008年6月至2010年5月,选择在北京安贞医院妇产科进行产前检查并分娩的孕妇80例,其中GDM孕妇40例(GDM组)、同期正常妊娠分娩孕妇40例(对照组),于孕早期(10～12周)、孕晚期(36～38周)、产后第3天及产后第42天分别抽取两组妇女空腹静脉血,用ELISA法测定其血清脂联素、瘦素和TNF-α水平；用颗粒增强免疫透射比浊法测定CRP水平；比较两组孕妇孕期4种细胞因子水平及其与稳态模型胰岛素抵抗指数(HOMA-IR)的相关性,以及4种细胞因子在产褥期的变化；通过受试者工作特征(ROC)曲线计算TNF-α曲线下面积,确定预测GDM的阈值.结果 (1)孕期细胞因子水平及其与HOMA-IR的相关性:孕早期GDM组脂联素水平为(5.7±1.8) mg/L,明显低于对照组的(8.1±2.7) mg/L,且脂联素水平与HOMA-IR呈负相关(r=-0.333,P＜0.05)；而孕早期GDM组瘦素水平为(28±10) μg/L、TNF-α水平为(10.0±3.4) ng/L、CRP水平为(4.7±1.1) mg/L,均明显高于对照组的(20±8)μg/L、(4.6±2.7) ng/L和(2.4±1.2) mg/L,且均与HOMA-IR呈正相关(r=0.411、0.529、0.308,P均＜0.05).孕晚期GDM组脂联素水平为(3.9±2.2) mg/L,明显低于对照组的(6.6±2.7) mg/L,且脂联素水平与HOMA-IR呈负相关(r=-0.344,P＜0.05)；而孕晚期GDM组瘦素水平为(37±13) μg/L、TNF-α水平为(12.7±2.6) ng/L、CRP水平为(6.7±3.6)mg/L,均明显高于对照组的(30±13) μg/L、(5.8±2.1)ng/L和(4.4±3.1)mg/L,且均与HOMA-IR呈正相关(r=0.414、0.487、0.285,P均＜0.05).多元线性回归分析显示,孕早期及孕晚期TNF-α水平均与HOMA-IR相关性最显著(r=0.390、0.284,P均＜0.05).(2)产褥期细胞因子水平及其与HOMA-IR的相关性:产后第3天,GDM组脂联素水平为(3.3±1.1) mg/L,明显低于对照组的(6.2±1.5) mg/L,且产后第3天脂联素水平与HOMA-IR呈负相关(r=-0.283,P＜0.05)；而产后第3天GDM组瘦素水平为(31±13) μg/L、TNF-α水平为(10.1±5.7) ng/L、CRP水平为(35.1±6.5) mg/L,均明显高于对照组的(21±15)μg/L、(5.6±3.0) ng/L、(30.5±8.5) mg/L,且瘦素及TNF-α水平均与HOMA-IR呈正相关(r=0.372、0.494,P均＜0.05).产后第42天,脂联素与HOMA-IR呈负相关(r=-0.299,P＜0.05)；而瘦素、TNF-α水平均与HOMA-IR呈正相关(r=0.401、0.442,P均＜0.05)；多元线性回归分析显示,产后第3天及第42天均是TNF-α水平与HOMA-IR相关性最显著(r=0.363、0.274,P均＜0.05).(3)DGM预测值:将GDM组孕妇孕早期数据进行ROC分析显示,TNF-α预测GDM发病的阈值为5.45 ng/L.结论 TNF-α可能成为孕期及产后预测及评价GDM及其预后的指标. 目的探討炎性細胞因子——腫瘤壞死因子α(TNF-α)、C反應蛋白(CRP)及脂肪細胞因子——脂聯素、瘦素水平與妊娠期糖尿病(GDM)髮病的相關性及4種細胞因子水平在產褥期的變化.方法 2008年6月至2010年5月,選擇在北京安貞醫院婦產科進行產前檢查併分娩的孕婦80例,其中GDM孕婦40例(GDM組)、同期正常妊娠分娩孕婦40例(對照組),于孕早期(10～12週)、孕晚期(36～38週)、產後第3天及產後第42天分彆抽取兩組婦女空腹靜脈血,用ELISA法測定其血清脂聯素、瘦素和TNF-α水平；用顆粒增彊免疫透射比濁法測定CRP水平；比較兩組孕婦孕期4種細胞因子水平及其與穩態模型胰島素牴抗指數(HOMA-IR)的相關性,以及4種細胞因子在產褥期的變化；通過受試者工作特徵(ROC)麯線計算TNF-α麯線下麵積,確定預測GDM的閾值.結果 (1)孕期細胞因子水平及其與HOMA-IR的相關性:孕早期GDM組脂聯素水平為(5.7±1.8) mg/L,明顯低于對照組的(8.1±2.7) mg/L,且脂聯素水平與HOMA-IR呈負相關(r=-0.333,P＜0.05)；而孕早期GDM組瘦素水平為(28±10) μg/L、TNF-α水平為(10.0±3.4) ng/L、CRP水平為(4.7±1.1) mg/L,均明顯高于對照組的(20±8)μg/L、(4.6±2.7) ng/L和(2.4±1.2) mg/L,且均與HOMA-IR呈正相關(r=0.411、0.529、0.308,P均＜0.05).孕晚期GDM組脂聯素水平為(3.9±2.2) mg/L,明顯低于對照組的(6.6±2.7) mg/L,且脂聯素水平與HOMA-IR呈負相關(r=-0.344,P＜0.05)；而孕晚期GDM組瘦素水平為(37±13) μg/L、TNF-α水平為(12.7±2.6) ng/L、CRP水平為(6.7±3.6)mg/L,均明顯高于對照組的(30±13) μg/L、(5.8±2.1)ng/L和(4.4±3.1)mg/L,且均與HOMA-IR呈正相關(r=0.414、0.487、0.285,P均＜0.05).多元線性迴歸分析顯示,孕早期及孕晚期TNF-α水平均與HOMA-IR相關性最顯著(r=0.390、0.284,P均＜0.05).(2)產褥期細胞因子水平及其與HOMA-IR的相關性:產後第3天,GDM組脂聯素水平為(3.3±1.1) mg/L,明顯低于對照組的(6.2±1.5) mg/L,且產後第3天脂聯素水平與HOMA-IR呈負相關(r=-0.283,P＜0.05)；而產後第3天GDM組瘦素水平為(31±13) μg/L、TNF-α水平為(10.1±5.7) ng/L、CRP水平為(35.1±6.5) mg/L,均明顯高于對照組的(21±15)μg/L、(5.6±3.0) ng/L、(30.5±8.5) mg/L,且瘦素及TNF-α水平均與HOMA-IR呈正相關(r=0.372、0.494,P均＜0.05).產後第42天,脂聯素與HOMA-IR呈負相關(r=-0.299,P＜0.05)；而瘦素、TNF-α水平均與HOMA-IR呈正相關(r=0.401、0.442,P均＜0.05)；多元線性迴歸分析顯示,產後第3天及第42天均是TNF-α水平與HOMA-IR相關性最顯著(r=0.363、0.274,P均＜0.05).(3)DGM預測值:將GDM組孕婦孕早期數據進行ROC分析顯示,TNF-α預測GDM髮病的閾值為5.45 ng/L.結論 TNF-α可能成為孕期及產後預測及評價GDM及其預後的指標.
목적 탐토염성세포인자——종류배사인자α(TNF-α)、C반응단백(CRP)급지방세포인자——지련소、수소수평여임신기당뇨병(GDM)발병적상관성급4충세포인자수평재산욕기적변화.방법 2008년6월지2010년5월,선택재북경안정의원부산과진행산전검사병분면적잉부80례,기중GDM잉부40례(GDM조)、동기정상임신분면잉부40례(대조조),우잉조기(10～12주)、잉만기(36～38주)、산후제3천급산후제42천분별추취량조부녀공복정맥혈,용ELISA법측정기혈청지련소、수소화TNF-α수평；용과립증강면역투사비탁법측정CRP수평；비교량조잉부잉기4충세포인자수평급기여은태모형이도소저항지수(HOMA-IR)적상관성,이급4충세포인자재산욕기적변화；통과수시자공작특정(ROC)곡선계산TNF-α곡선하면적,학정예측GDM적역치.결과 (1)잉기세포인자수평급기여HOMA-IR적상관성:잉조기GDM조지련소수평위(5.7±1.8) mg/L,명현저우대조조적(8.1±2.7) mg/L,차지련소수평여HOMA-IR정부상관(r=-0.333,P＜0.05)；이잉조기GDM조수소수평위(28±10) μg/L、TNF-α수평위(10.0±3.4) ng/L、CRP수평위(4.7±1.1) mg/L,균명현고우대조조적(20±8)μg/L、(4.6±2.7) ng/L화(2.4±1.2) mg/L,차균여HOMA-IR정정상관(r=0.411、0.529、0.308,P균＜0.05).잉만기GDM조지련소수평위(3.9±2.2) mg/L,명현저우대조조적(6.6±2.7) mg/L,차지련소수평여HOMA-IR정부상관(r=-0.344,P＜0.05)；이잉만기GDM조수소수평위(37±13) μg/L、TNF-α수평위(12.7±2.6) ng/L、CRP수평위(6.7±3.6)mg/L,균명현고우대조조적(30±13) μg/L、(5.8±2.1)ng/L화(4.4±3.1)mg/L,차균여HOMA-IR정정상관(r=0.414、0.487、0.285,P균＜0.05).다원선성회귀분석현시,잉조기급잉만기TNF-α수평균여HOMA-IR상관성최현저(r=0.390、0.284,P균＜0.05).(2)산욕기세포인자수평급기여HOMA-IR적상관성:산후제3천,GDM조지련소수평위(3.3±1.1) mg/L,명현저우대조조적(6.2±1.5) mg/L,차산후제3천지련소수평여HOMA-IR정부상관(r=-0.283,P＜0.05)；이산후제3천GDM조수소수평위(31±13) μg/L、TNF-α수평위(10.1±5.7) ng/L、CRP수평위(35.1±6.5) mg/L,균명현고우대조조적(21±15)μg/L、(5.6±3.0) ng/L、(30.5±8.5) mg/L,차수소급TNF-α수평균여HOMA-IR정정상관(r=0.372、0.494,P균＜0.05).산후제42천,지련소여HOMA-IR정부상관(r=-0.299,P＜0.05)；이수소、TNF-α수평균여HOMA-IR정정상관(r=0.401、0.442,P균＜0.05)；다원선성회귀분석현시,산후제3천급제42천균시TNF-α수평여HOMA-IR상관성최현저(r=0.363、0.274,P균＜0.05).(3)DGM예측치:장GDM조잉부잉조기수거진행ROC분석현시,TNF-α예측GDM발병적역치위5.45 ng/L.결론 TNF-α가능성위잉기급산후예측급평개GDM급기예후적지표.
Objective To investigate the relationship between inflammatory factors,including C-reactive protein( CRP),tumor necrosis factor alpha (TNF-α),adiponectin,leptin and gestational diabetes mellitus (GDM) and their changes in puerperiunr Methods From June 2008 to May 2010,40 cases with gestational diabetes mellitus,40 cases of normal pregnancy were enrolled in this study.Fasting venous blood were obtained at early pregnancy (10 - 12 weeks),late pregnancy (36 -38 weeks) and day 3 and 42 of postpartum.Serumal adiponectin,leptin and TNF-α were measured by ELISA,and serumal CRP were measured by particle enhanced immunoturbidimetric method.The levels of those 4 cytokines and homeostasis model assessment insulin resistance (HOMA-IR) index were compared between two groups.And the changes of 4 cytokines were calculated in puerperium.The receiver operating characteristic (ROC) for TNF-α predicting GDM was designed.Results ( 1 ) The relationship between cytokines and HOMA-IR:the levels of adiponectin of (5.7 ± 1.8 ) mg/L in the GDM group were significantly lower than ( 8.1 ± 2.7 ) mg/L in control group in early pregnancy,and the level of adiponectin was negatively correlated with HOMA-IR (r=-0.333,P＜0.05).The levels of (28 ± 10) μg/L of leptin,( 10.0 ±3.4) ng/L of TNF-α and (4.7 ± 1.1 ) mg/L of CRP in GDM group were significantly higher than ( 20 ± 8 ) μ,g/L of leptin,(4.6 ±2.7) ng/L of TNF-α,(2.4 ± 1.2 ) mg/L of CRP in control group,which were positively correlated with HOMA-IR ( r =0.411,0.529,0.308,all P ＜ 0.05 ).In late pregnancy,the level of adiponectin ( 3.9 ±2.2) mg/L in the GDM group was significantly lower than ( 6.6 ± 2.7 ) mg/L in control group,and the level of adiponectin was negatively correlated with HOMA-IR ( r =- 0.344,P ＜ 0.05 ).The levels of ( 37 ±13) μg/L of leptin,( 12.7 ±2.6) ng/L of TNF-α and (6.7 ±3.6) mg/L of CRP in the GDM group were significantly higher than ( 30 ± 13 ) μg/L of leptin,(5.8 ± 2.1 ) ng/L of TNF-α,( 4.4 ± 3.1 ) mg/L of CRP in control group,which were positively correlated with HOMA-IR (r =0.414,0.487,0.285,all P ＜0.05).Multiple linear regression analysis showed that the level of TNF-α at early and late pregnancy was most correlated with HOMA-IR ( r =0.390,0.284,all P ＜ 0.05 ).( 2 ) The level of the cytokines and HOMA-IR in puerperium:at day 3 of postpartum,the level of adiponectin of (3.3 ± 1.1) mg/L in the GDM group was significantly lower than (6.2 ± 1.5 ) mg/L in control group,which was negatively correlated with HOMA-1R (r =- 0.283,P ＜ 0.05 ).The levels of ( 31 ± 13 ) μg/L of leptin,( 10.1 ± 5.7 ) ng/L of TNF-α and (35.1 ±6.5) mg/L of CRP in the GDM group were significantly higher than (21 ± 15) μg/L of leptin,(5.6 ± 3.0) ng/L of TNF-α,(30.5 ± 8.5) mg/L of CRP in control group.And leptin and TNF-α levels were positively correlated with HOMA-IR (r=0.372,0.494,all P ＜0.05).At day 42 of postpartum,the level of adiponectin in GDM group was negatively correlated with HOMA-IR ( r =- 0.299,P ＜ 0.05 ),and the levels of leptin and TNF-α were positively correlated with HOMA-IR ( r =0.401,0.442,all P ＜0.05 ).Multiple linear regression analysis showed that the level of TNF-αt at day 3 and day 42 was most correlated with HOMA-IR ( r =0.363,0.274,all P ＜ 0.05 ).( 3 ) ROC analysis of data from early pregnancy showed that the threshold for TNF-α to predict GDM was 5.45 ug/L.Conclusion TNF-ot might be the index to predict GDM and evaluate prognosis.