基于某医院纵向体检资料的血清胆红素与代谢综合征关联性研究

发布时间：2018-05-06 22:26

本文选题：代谢综合征 + 总胆红素　；参考：《山东大学》2017年硕士论文

【摘要】：研究背景代谢综合征(Metabolic Syndrome,MS)是指多种相互关联的代谢异常在个体内聚集的病理状态,包含高血压、高血糖、血脂异常和肥胖,是心血管疾病、慢性肾脏疾病和癌症等疾病的重要危险因素。随着经济的发展和生活方式的转变,MS的患病率在全球范围内逐年上升,已成为严重威胁人类健康的公共卫生问题。基于2010-2012年中国居民营养与健康状况监测数据分析发现,我国多18岁成人MS的患病率为11.0%,过去10年间MS患者增加约5000万人。因此,MS的预防与控制对我国人民的健康十分重要。胆红素是血红素代谢产物,常被临床用于辅助诊断溶血、新生儿黄疸、肝胆疾病等。越来越多的研究表明胆红素是一种强有力的抗氧化物质,且具有抗炎特性。目前,学术界普遍认为氧化应激及慢性炎症反应是MS的重要病因。此外,研究表明,胆红素水平的降低能增加心血管疾病、癌症、2型糖尿病等疾病的发生及患病风险,而这些疾病与MS密切相关。因此,血清胆红素可能具有保护机体抵抗MS发生的作用。关于血清胆红素与MS的关系,学者们已作了一些研究,研究现况如下:1)多为横断面研究,无法判定时间顺序性;2)现有的队列研究多忽视了血清胆红素水平在随访过程中的变化,仅分析基线血清胆红素水平与MS发生的关系,可能造成一定偏倚;3)不同性别、年龄和种族等人口学特征可能会影响血清胆红素与MS的关系,然而目前关于中国人群的纵向研究仍然缺乏;4)血清间接胆红素(Indirect Bilirubin,,IBIL)和直接胆红素(Direct Bilirubin,DBIL)与 MS 的关系可能存在差异,血清总胆红素(Total Bilirubin,TBIL)水平是IBIL与DBIL水平之和,然而以往研究主要探讨血清TBIL与MS的关系,较少涉及IBIL与DBIL;5)目前关于血清胆红素与MS关系的研究结果不尽一致,部分研究发现两者呈负相关,而有些研究却发现两者无关。因此,血清胆红素与MS的关系仍有许多未知之处需要被研究。研究目的1.分析血清TBIL、IBIL和DBIL水平与MS发生的关系;2.分析血清TBIL、IBIL和DBIL水平与MS各组分的关系。研究对象与方法本研究基于山东省东营市胜利油田中心医院2006年1月-2015年12月健康体检资料,构建动态体检队列。研究对象的纳入:将首次体检未患MS且至少包含3次体检记录的成年人纳入本研究。研究对象的排除:排除基线乙肝表面抗原阳性、丙肝抗体阳性、肝功能异常、患有肝病和患有心衰、肾衰、癌症等严重疾病者。收集的指标包括研究对象的一般情况、体格检查和实验室检测指标。本研究依据中华医学会糖尿病学分会2004年制定的标准诊断MS,利用SPSS 18.0软件及SAS 9.3软件进行统计分析,采用广义估计方程(Generalized Estimating Equations.GEE)分析胆红素与MS的关系。首先进行单因素分析挑选与MS发生可能有关的因素,然后结合P0.10的统计学标准与医学实际意义选择变量纳入多因素GEE模型中。本研究采用"Logit"为联接函数,分布设为"二项分布",作业相关矩阵设为"等相关","随访年"用于规定层内重复测量时间顺序,血清胆红素水平采用四分位数水平表示并以第一四分位数水平为参照进行GEE分析。研究结果1.研究对象的基本情况:本研究共纳入9154人,平均年龄为41.1 ±10.8岁;其中女性3363人,平均年龄为40.1±10.3岁;男性5791人,平均年龄为41.7±11.0岁。9年随访过程中,每名研究对象平均随访4.4±2.2年,共有2126人发生MS,发病密度为5.33/100人年。女性MS的发病密度为2.39/100人年,男性MS的发病密度为7.28/100人年,男性MS发病密度高于女性(u=22.902,P0.001)。基线具备0、1和2个MS组分的研究对象构成比分别为42.7%、30.7%和26.6%。2.血清胆红素水平与MS关系的多因素GEE分析:IBIL水平与MS的发生无统计学关联;TBIL和DBIL水平与MS的发生呈负相关;以最低水平组为参照,TBIL最高水平组MS的相对危险度及95%置信区间为0.839(0.727-0.968),DBIL最高水平组MS的相对危险度及95%置信区间为0.588(0.502-0.687)。经线性趋势检验发现,TBIL和DBIL水平与MS的发生呈现剂量反应关系(P0.05)。3.不同亚组研究人群多因素GEE分析胆红素与MS的关系:1)在不同性别和基线年龄的研究人群中,血清IBIL水平与MS的发生无统计学关联,血清TBIL和DBIL与MS的关系在不同性别中存在差异。女性中,血清TBIL在各年龄组均与MS的发生无统计学关联,DBIL在低年龄组(≤44岁)中与MS的发生呈负相关;男性中,血清TBIL在低年龄组中与MS的发生呈负相关,DBIL在低年龄组及中年龄组(45-54岁)中与MS的发生均呈负相关。2)依据基线具备MS组分个数分层分析发现,DBIL水平与MS的发生风险呈负相关,该负相关关系随着基线具备MS组分个数增多而减弱。4.血清胆红素水平与MS各组分关系的多因素GEE分析:在基线未具备任何MS组分的研究人群中,血清TBIL水平与血脂异常和超重/肥胖呈负相关,血清IBIL水平与血脂异常呈负相关,血清DBIL水平与高血压、血脂异常和超重/肥胖呈负相关。研究结论1.低血清DBIL水平可能是MS的危险因素。血清TBIL水平与MS的负相关关系可能是由DBIL水平与MS的负相关关系所造成。2.血清DBIL水平与MS的负相关关系在机体代谢紊乱程度较严重时被削弱。
[Abstract]:Metabolic Syndrome (MS) refers to the pathological state of a variety of interrelated metabolic abnormalities in the individual, including hypertension, hyperglycemia, dyslipidemia, and obesity. It is an important risk factor for cardiovascular disease, chronic kidney disease and cancer. With the economic development and lifestyle changes, MS The prevalence rate has risen year by year worldwide and has become a serious public health problem which threatens human health seriously. Based on the data analysis of the monitoring data of Chinese residents' nutrition and health status for 2010-2012 years, the prevalence rate of MS in China's 18 year old adults is 11% and the MS patients have increased by about 50 million in the past 10 years. Therefore, the prevention and control of MS is to the people of our country Bilirubin is a heme metabolite, which is often used to assist in the diagnosis of hemolysis, neonatal jaundice and hepatobiliary diseases. More and more studies have shown that bilirubin is a powerful antioxidant and has the characteristics of anti-inflammatory. At present, the academic community has generally recognized that oxidative stress and chronic inflammatory reaction are important diseases of MS. In addition, studies have shown that the reduction of bilirubin levels can increase the incidence and risk of diseases such as cardiovascular disease, cancer, type 2 diabetes and other diseases. These diseases are closely related to MS. Therefore, serum bilirubin may have the protective effect of protecting the body against the occurrence of MS. Some studies have been made by scholars on the relationship between serum bilirubin and MS. The present status of the study is as follows: 1) most of the cross-sectional studies can not determine the time sequence; 2) existing cohort studies overlooked the changes in serum bilirubin levels during follow-up, and only analyzed the relationship between the baseline serum bilirubin level and the occurrence of MS, possibly resulting in a certain bias; 3) the demographic characteristics of different sexes, age and race may be reflected. The relationship between ringing serum bilirubin and MS, however, there is still a lack of longitudinal study on Chinese people; 4) there may be differences in the relationship between serum indirect bilirubin (Indirect Bilirubin, IBIL) and direct bilirubin (Direct Bilirubin, DBIL) and MS, and the level of total serum total bilirubin (Total Bilirubin, TBIL) is the sum of the level of IBIL and MS, however, however, The study mainly discussed the relationship between serum TBIL and MS, less related to IBIL and DBIL; 5) the results of the study on the relationship between serum bilirubin and MS are not consistent. Some studies have found that there is a negative correlation between the two and some studies have found that the relationship between serum bilirubin and MS still has many unknowns to be studied. 1. analysis of the relationship between serum TBIL, IBIL and DBIL levels with MS; 2. analysis of the relationship between serum TBIL, IBIL and DBIL and MS components. Based on the healthy physical examination data of the Central Hospital of Shengli Oil Field in Dongying, Shandong province in January 2006, the dynamic physical examination queue was constructed. The subjects were excluded from MS and at least 3 medical records. The exclusion of subjects: excluding baseline hepatitis B surface antigen positive, hepatitis C antibody positive, liver dysfunction, liver disease and heart failure, kidney failure, cancer and other serious diseases. This study was based on the standard diagnostic MS made by the Chinese Medical Association for diabetes in 2004, using SPSS 18 software and SAS 9.3 software to analyze the relationship between bilirubin and MS by the generalized estimation equation (Generalized Estimating Equations.GEE). The first advanced single factor analysis may be related to the possible occurrence of MS. And then combined with the statistical standard of P0.10 and the selection variables of practical significance of medicine into the multi factor GEE model, this study uses "Logit" as a join function, the distribution is set as "two distribution", the job correlation matrix is set as "equal correlation", "follow up year" is used to specify the time sequence of repeated measurements in the layer, and the level of serum bilirubin is divided into four points. GEE analysis was carried out with the number level and the level of the first four quantiles. Results 1. the basic situation of the study was included in the study: This study included 9154 people with an average age of 41.1 + 10.8 years, of which 3363 were women, the average age was 40.1 + 10.3 years, and the average age was 41.7 + 11 years in the follow-up process of each study. The average follow-up was 4.4 + 2.2 years. A total of 2126 people had MS and the density was 5.33/100 year. The incidence density of female MS was 2.39/100 year, the density of male MS was 7.28/100 year, and the density of MS in male was higher than that of women (u=22.902, P0.001). The ratio of baseline with 0,1 and 2 MS components was 42.7%, 30.7% and 26.6%.2. sera, respectively. The multifactor GEE analysis of the relationship between bilirubin level and MS: IBIL level had no statistical correlation with the occurrence of MS; TBIL and DBIL levels were negatively correlated with the occurrence of MS; the relative risk and 95% confidence interval of the highest level group of TBIL were 0.839 (0.727-0.968), and the relative risk and 95% confidence interval of MS were the highest level group of TBIL. 0.588 (0.502-0.687). Meridional trend test found that TBIL and DBIL levels were in a dose-response relationship with MS (P0.05).3. in different subgroups, the relationship between multiple factors and GEE analysis of bilirubin and MS: 1) there was no statistical correlation between the level of serum IBIL and the occurrence of MS in the study population of different sex and baseline age, serum TBIL and DBIL. The relationship with MS was different in different sexes. In women, there was no statistical correlation between serum TBIL and MS in all age groups. DBIL was negatively correlated with MS in low age group (less than 44 years old); in male, TBIL was negatively correlated with MS in low age group and DBIL in low age group and middle age group (45-54 years old) and MS hair. A negative correlation.2) based on the baseline MS stratified analysis found that the level of DBIL was negatively correlated with the risk of MS, and the negative correlation was associated with the multifactor GEE analysis of the.4. serum bilirubin level and MS components with the increase in the number of MS groups in the baseline: in the study population that had no MS component at baseline, Serum TBIL level is negatively correlated with dyslipidemia and overweight / obesity, serum IBIL level is negatively correlated with dyslipidemia, serum DBIL level is negatively correlated with hypertension, dyslipidemia and overweight / obesity. Conclusion 1. low serum DBIL level may be a risk factor for MS. The negative correlation between serum TBIL level and MS may be from DBIL level and M. Negative correlation between S and the negative correlation between.2. serum DBIL level and MS is weakened when the body's metabolic disorder is more serious.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589

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