锌α2糖蛋白指数—评价胰岛素敏感性的简易指标

发布时间：2018-09-07 21:54

【摘要】：第一部分在肥胖合并不同糖耐量人群中初步探究锌α2糖蛋白与胰岛素敏感性的关系目的：在肥胖合并不同糖耐量人群中,初步探究锌葩糖蛋白(ZAG)与胰岛素敏感性(IS)的关系。方法：共纳入211例研究人群,其中肥胖合并正常糖耐量患者67例,肥胖合并糖耐量减低初诊患者61例,肥胖合并2型糖尿病初诊患者83例。受试者均进行口服葡萄糖耐量试验(OGTT)、口服葡萄糖胰岛素释放试验(OGIRT),与人体测量指标及临床指标检测。游离ZAG水平以酶联免疫吸附试验(ELISA)测定。首先,用t检验比较ZAG、人体测量指标及临床指标,在不同疾病组别中的统计学差异；其次,用直线相关分析及偏相关分析,探究ZAG与稳态模型胰岛素抵抗指数(HOMA-IR)、人体测量指标及临床指标的相关性；再则,用多元线性回归探究ZAG与胰岛素敏感性的关系。结果：肥胖合并2型糖尿病组的腰围(WC)、臀围(HC)、腰臀比(WHR)、收缩压(SBP)、舒张压(DBP)、空腹血浆葡萄糖(FPG)、餐后2小时血浆葡萄糖(2h-PG)、HbA1c、总胆固醇(TC)、甘油三酯(TG)、HOMA-IR、空腹血清胰岛素(FIns)及餐后2小时血清胰岛素(2h-Ins)均高于肥胖合并正常糖耐量组(P0.05或P0.01),相反,高密度脂蛋白胆固醇(HDL-C)、游离ZAG水平则低于肥胖合并正常糖耐量组(P0.01)。在校正性别、年龄后,ZAG与HOMA-IR呈负相关。多元线性回归分析提示：YZAG= 0.957 XHDL-C-1.290XBMI-2.474XHOMA-IR+87.112 (R=0.583, P0.01)。结论：在肥胖合并不同程度糖耐量人群中,ZAG与胰岛素敏感性呈正相关。第二部分初步探究锌α2糖蛋白指数作为多囊卵巢综合征患者胰岛素敏感性的简易评价指标目的：用高胰岛素-正葡萄糖钳夹术(EHC)作为评价标准,将锌葩糖蛋白指数(ZAG指数),即Ln[锌α2糖蛋白/稳态模型胰岛素抵抗指数](Ln[ZAG/HOMA-IR]),与部分现有的评价胰岛素敏感性的指标进行对比,初步探究ZAG指数作为简易评价指标,用于评价多囊卵巢综合征(PCOS)患者的胰岛素敏感性(IS)。方法：共纳入202例研究人群,其中PCOS患者102例,正常对照100例,研究人群均进行EHC,以评定其胰岛素敏感性,同时进行OGTT、 OGIRT与人体测量指标及临床指标检测。游离ZAG、脂联素(ADI)水平用ELISA测定。首先,用t检验比较人体测量指标及临床指标在PCOS组与对照组的统计学差异,同时比较ZAG指数、HOMA-IR、 ADI/HOMA-IR等不同指数在胰岛素抵抗组和非抵抗组中的差异。其次,采用偏相关分析探究ZAG指数与人体测量指标及临床指标的相关性,同时用偏相关分析探究ZAG指数、HOMA-IR、ADI/HOMA-IR等指数与M值(EHC稳态期葡萄糖输注率)的相关性。并以多元线性回归进一步探究ZAG指数与M值的关系。进一步采用Logistic回归探究对于胰岛素敏感性,ZAG指数、ADI/HOMA-IR等不同指数是保护性因子还是危险因子。再则,用加权K检验及Pearson列联系数分析ZAG指数与M值的三分位分布区间的一致性。最后,以受试者工作特征(ROC)曲线的曲线下面积(AUC)、Youden指数评估上述指数诊断胰岛素敏感性的效能,并分析上述指标诊断胰岛素敏感性的最佳切点值,及相应的灵敏度和特异度。结果：胰岛素抵抗组的ZAG指数、ADI/HOMA-IR低于非胰岛素抵抗组。相反地,胰岛素抵抗组的TG/HDL-C、TyG、I/G、HOMA-IR则高于非抵抗组。偏相关提示ZAG指数与M值的相关系数为(r=0.779,P0.01),不低于HOMA-IR及ADI/HOMA-IR与M值的相关系数(r=：-0.623,P0.01)及(r=0.604,P0.01),同时不低于TyG (r=-0.394, P0.01)、I/G (r=-0.598, P0.01)及TG/HDL-C (r=-0.237, P＜0.01)与M值的相关系数。多元线性回归提示：YZAG index=4.277+0.1 XM value-0.079XFIns-0.248XFPG (R2=0.896, P0.001)。此外,Logistic回归提示ZAG指数与ADI/HOMA-IR是胰岛素敏感性的保护因子,而TyG.TG/HDL-C、HOMA-IR、I/G则为危险因子。再则,在ZAG指数与M值的三分位分布区间的一致性检验中,加权K检验一致性系数为0.502,Pearson列联系数r=0.741。最后,在ROC曲线分析中,ZAG指数诊断胰岛素敏感性的曲线下面积(AUC)接近1,且不低于其余指数的AUC。在研究人群中ZAG指数最佳切点值为2.97,对应的灵敏度和特异度分别为87.8%和90.8%,Youden指数=0.786。结论：ZAG指数可作为PCOS患者胰岛素敏感性的简易评价指标。
[Abstract]:The first part explores the relationship between zinc alpha 2 glycoprotein and insulin sensitivity in obese subjects with different glucose tolerance Objective: To explore the relationship between zinc glycoprotein (ZAG) and insulin sensitivity (IS) in obese subjects with different glucose tolerance. Sixty-seven obese patients with impaired glucose tolerance and 83 obese patients with type 2 diabetes mellitus were enrolled in the study. Oral glucose tolerance test (OGTT), oral glucose insulin release test (OGIRT) and anthropometric and clinical parameters were measured. Free ZAG levels were measured by enzyme-linked immunosorbent assay (ELISA). T test was used to compare ZAG, anthropometric indicators and clinical indicators in different disease groups; secondly, linear correlation analysis and partial correlation analysis were used to explore the correlation between ZAG and homeostasis model insulin resistance index (HOMA-IR), anthropometric indicators and clinical indicators; secondly, multiple linear regression was used to explore the relationship between ZAG and insulin. Results: The waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), plasma glucose (2h-PG), HbA1c, total cholesterol (TC), triglyceride (TG), HOMA-IR, fasting serum insulin (FIns) and 2 h-postprandial serum insulin (2h-PG) in obese patients with type 2 diabetes mellitus were measured. Ins was higher than obesity with normal glucose tolerance (P 0.05 or P 0.01), whereas HDL-C and free ZAG levels were lower than obesity with normal glucose tolerance (P 0.01). After adjusting for sex and age, ZAG was negatively correlated with HOMA-IR. R = 0.583, P 0.01). Conclusion: ZAG is positively correlated with insulin sensitivity in obese patients with different degrees of glucose tolerance. Zinc glycoprotein index (ZAG index), i.e. Ln [Zinc alpha2 glycoprotein/homeostasis model insulin resistance index] (Ln [ZAG/HOMA-IR]), was compared with some existing indicators for assessing insulin sensitivity. ZAG index was used as a simple index for assessing insulin sensitivity (IS) in patients with polycystic ovary syndrome (PCOS). A total of 202 subjects including 102 PCOS patients and 100 normal controls were enrolled in the study. EHC was performed to assess insulin sensitivity. OGTT, OGIRT, anthropometric and clinical indices were detected. Levels of free ZAG and adiponectin (ADI) were measured by ELISA. Firstly, anthropometric and clinical indices were compared in PCO with t test. Statistical differences between S group and control group were compared, and ZAG index, HOMA-IR, ADI/HOMA-IR and other indicators in insulin resistance group and non-resistant group were compared. Secondly, the correlation between ZAG index and anthropometric indicators and clinical indicators was explored by partial correlation analysis, and ZAG index, HOMA-IR, ADI/HOMA-IR and other indicators were explored by partial correlation analysis. The relationship between ZAG index and M value was further explored by multivariate linear regression. Logistic regression was used to explore whether insulin sensitivity, ZAG index, ADI/HOMA-IR and other indices were protective factors or risk factors. The consistency between ZAG index and M value was analyzed. Finally, the effectiveness of ZAG index in diagnosing insulin sensitivity was evaluated by AUC and Youden index of ROC curve. The best cut-off point of ZAG index in diagnosing insulin sensitivity and the corresponding sensitivity and specificity were analyzed. On the contrary, TG / HDL - C, TyG, I / G, HOMA - IR in insulin resistance group were higher than those in non - insulin resistance group. Partial correlation suggested that the correlation coefficient between ZAG index and M value was (r = 0.779, P 0.01), not lower than that between HOMA - IR and ADI / HOMA - IR and M value (r = - 0.623, P 0.01) and (r = 0.604, P 0.01). The correlation coefficients of TyG (r = - 0.394, P 0.01), I / G (r = - 0.598, P 0.01) and TG / HDL - C (r = - 0.237, P < 0.01) with M value were not lower than those of TyG (r = - 0.394, P 0.01). Multivariate linear regression analysis suggested that YZAG index = 4.277 + 0.1 XM value - 0.079XFIns - 0.248 XFPG (R2 = 0.896, P 0.001) was a protective factor for insulin sensitivity, and logistic regression suggested that ZMAG index and ADI / HO were protective factors for insulin sensitivity. TyG.TG/HDL-C, HOMA-IR, and I/G were risk factors. Furthermore, in the consistency test between ZAG index and M value, the consistency coefficient of weighted K test was 0.502, and the Pearson contingency number r = 0.741. Finally, in the ROC curve analysis, the area under the curve (AUC) of ZAG index for insulin sensitivity diagnosis was close to 1 and not lower than the other indexes. The best cut-off point of ZAG index was 2.97, and the sensitivity and specificity were 87.8% and 90.8% respectively. Youden index was 0.786. Conclusion: ZAG index can be used as a simple index to evaluate the insulin sensitivity of PCOS patients.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R589.2;R587.1

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