代谢正常肥胖转归糖尿病风险的队列研究及FTO SNP rs9939609与糖尿病关系的研究

发布时间：2018-06-18 17:33

本文选题：肥胖 + 代谢正常肥胖(MHO)　；参考：《西南医科大学》2017年硕士论文

【摘要】：第一部分代谢正常肥胖转归糖尿病风险的前瞻性队列研究背景和目的:随着社会的发展,城市化的进程,人们正活方式的改变,近几十年,我国超重和肥胖的比例明显的增加,糖尿病患病率也呈逐年上升的趋势。众所周知,肥胖是糖尿病的危险因素。近年研究发现不同代谢状态的肥胖人群在糖尿病发病率上存在差异,称为肥胖的不同亚型。代谢正常肥胖(MHO)以肥胖但胰岛素敏感为特征,与代谢异常肥胖(MUHO)在2型糖尿病、心血管疾病等发病风险、体脂分布、炎症水平等方面存在差异。MHO患病率在不同研究中因界定标准及地区等不同结果差异较大,与其他肥胖亚型相比,MHO是否增加糖尿病发病风险尚存在争议。本文旨在了解泸州社区40岁以上代谢正常肥胖(MHO)患病率及随访3年糖尿病发病率情况。研究对象和方法:2011年4月-8月采用多级整群抽样方法,对泸州市3个社区不同街道40岁以上居民进行问卷调查、体格检查、生化检测等,所有研究对象均进行标准化问卷调查,收集一般情况(姓名、性别、年龄、社区等),既往高血压、糖尿病家族史等基本信息。受试者均接受常规体格检查,包括测量腰围、臀围、身高、体重、静息时血压等。问卷调查的填写和体格检查均由经过培训的医学研究生及本科生完成。生化检测内容包括:空腹血糖(FBS)、OGTT(口服葡萄糖耐量试验)2h血糖、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(Hb A1C)等。空腹血标本要求禁食至少8h。于2014年6月-10月对其进行随访调查,随访调查内容及要求同基线。结果:排除失访及资料不全者,本调查共计纳入2442例非糖尿病人群(其中男性749例,占比30.7%),平均年龄59.56±9.57,女性1693例,平均年龄56.36±9.02,P0.001,差异具有统计学意义。MHO、代谢正常非肥胖(MHNO)、代谢异常肥胖(MUHO)、代谢异常非肥胖(MUHNO)分别占比14.8%、45.3%、19.5%、20.4%,男、女MHO患病率分别为11.2%、15.4%。按年龄分层分析,结果显示40-45岁、56-70岁、70岁以上人群MHO患病率分别为14.8%、14.3%、9.6%。随访3年,共计248例转归为糖尿病,与MHNO相比,MHO、MUHO、MUHNO糖尿病发病风险分别是MHNO的1.64(95%CI,0.99~2.70),5.23(95%CI,3.72~7.36),3.93(95%CI,2.74~5.64)倍,女性MHO糖尿病发病风险是MHNO的2.05(95%CI,1.15~3.65)倍。按性别分层分析,男性MHO、MUHO、MUHNO糖尿病发病风险分别是MHNO的0.88、3.53、2.53倍,女性分别是2.05、6.23、4.85倍。MHO组随访3年后甘油三酯(TG)、收缩压(SBP)、舒张压(DBP)、空腹血糖(FBS)、OGTT2h血糖指标异常百分比分别为34.3%、39.4%、22.6%、8.3%、43.4%,与MHNO组相比明显增加(p0.05)。结论:1.MHO在女性和相对低龄的人群中患病率更高。2.MHO组糖尿病发病率明显低于MUHO、MUHNO组,女性MHO组糖尿病发病率高于MHNO组。3.与MHNO相比,MHO更易发生代谢异常。第二部分FTO SNP rs9939609与糖尿病关系的前瞻性队列研究背景和目的:FTO基因是通过全基因组关联分析(GWAS)技术发现的一个肥胖易感基因。FTO基因是到目前为止在欧洲人群的研究中唯一多次重复并且成功的肥胖易感基因。国内一些研究也表明FTO基因与肥胖的发生具有相关性。此外,有研究报道称FTO基因与T2DM的发生相关,但FTO与糖尿病的相关性是否独立于BMI而存在,在现有的相关研究中,结果并不一致。本文旨在探讨FTO基因rs9939609位点多态性与糖尿病的相关性。研究对象和方法:2011年4月-8月采用多级整群抽样方法,对泸州市3个社区不同街道40岁以上居民进行问卷调查、体格检查、生化检测,于2014年6月-10月对其进行随访调查。排除失防及资料不全者,采用简单随机抽样的方法(随机数表法)抽取500例受试者,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP或CAPs)的方法测定基因位点多态性。结果:共计纳入496例非糖尿病受试者,其中男性188例,女性308例,腹围正常311例,腹型肥胖185例。FTO基因rs9939609位点A等位基因分布频率为15.3%。正常体重和肥胖组TA基因型频率分别为20.1%、31.8%,AA型分别为1.6%、3.3%(P0.05)。TAAA基因型基线腰围(Waist circumference,WC)、BMI指标值较TT基因型升高(P0.05)。随访3年,TT和TAAA基因型糖尿病发病率分别为10.1%、16.7%,p=0.042,OR=1.789,95%CI(1.017~3.147)。Logistic回归分析,校正BMI、血糖、血脂等影响后,结果显示FTO基因rs9939609位点A等位基因不是非糖尿病人群转归糖尿病的危险因素。结论:1.FTO基因rs9939609位点与肥胖(以BMI界定)存在相关性,A等位基因增加肥胖患病风险。2.随访3年,TAAA型糖尿病发病率较TT型高。AATA基因型糖尿病发病风险高于TT型可能与BMI介导相关。
[Abstract]:The first part is the background and purpose of the prospective cohort study on the risk of metabolism of normal obesity to diabetes: with the development of society, the process of urbanization and the change of people's way of living, the proportion of overweight and obesity in China has increased significantly in recent decades, and the prevalence rate of diabetes is also increasing year by year. Risk factors. In recent years, it is found that there are differences in the incidence of diabetes in obese people with different metabolic states, known as different subtypes of obesity. Metabolic normal obesity (MHO) is characterized by obesity but insulin sensitivity, and metabolic abnormality of obesity (MUHO) in type 2 diabetes, heart and blood tube diseases, body fat distribution, and inflammation levels. The difference of the prevalence rate of.MHO in different studies is quite different from the criteria and regions. Compared with other obese subtypes, it is still controversial whether MHO increases the risk of diabetes. The purpose of this study is to understand the prevalence of metabolic normal obesity (MHO) over 40 years old in the community and the incidence of diabetes in the 3 years of follow-up. And methods: a multilevel cluster sampling method was used in -8 month of April 2011. The questionnaire survey, physical examination, biochemical test and so on were conducted in 3 communities of 3 communities in different communities. All the subjects were standardized to collect the general situation (name, sex, age, community, etc.), past hypertension, family history of diabetes and so on. All subjects received routine physical examination, including waist circumference, hip circumference, height, weight, and resting blood pressure. The questionnaire survey was completed by trained medical graduate students and undergraduate students. Biochemical tests included fasting blood glucose (FBS), OGTT (oral glucose tolerance test) 2H blood sugar, triglyceride (TG), total Cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (Hb A1C), etc.. Fasting blood specimens require a fasting at least 8h. in -10 month of June 2014 to follow up the survey, follow up and request the same baseline. The average age was 59.56 + 9.57, the average age was 59.56 + 9.57, and the average age was 56.36 + 9.02, P0.001. The difference was.MHO, the metabolic abnormal obesity (MHNO), the metabolic abnormal obesity (MUHO), and the metabolic abnormality (MUHNO) accounted for 14.8%, 45.3%, 19.5%, 20.4%, male and female MHO prevalence rate respectively. For 11.2%, 15.4%. was analyzed by age stratification. The results showed that 40-45 years old, 56-70 years old and 70 years old were 14.8%, 14.3%, and 9.6%. were followed up for 3 years and 248 were converted to diabetes. Compared with MHNO, the risk of MHO, MUHO, MUHNO diabetes was 1.64 (95%CI, 0.99~2.70), 5.23 (95%CI, 3.72~7.36), 3.93, respectively times, respectively. The risk of MHO diabetes in women is 2.05 (95%CI, 1.15~3.65) times of MHNO. According to sex stratification, the risk of MHO, MUHO, and MUHNO diabetes in men is 0.88,3.53,2.53 times of MHNO, respectively, and women in the 2.05,6.23,4.85 times.MHO group are followed up for 3 years after the follow-up, systolic pressure, diastolic blood pressure, fasting blood glucose, and blood sugar index The abnormal percentages were 34.3%, 39.4%, 22.6%, 8.3%, 43.4%, compared with the MHNO group (P0.05). Conclusion: the incidence of 1.MHO in women and relatively low age groups was higher than that in group.2.MHO and MUHNO, and the incidence of diabetes in female MHO group was higher than that of MHNO group.3. and MHNO, MHO was more likely to have metabolic abnormalities. Second Background and purpose of a prospective cohort study on the relationship between partial FTO SNP rs9939609 and diabetes: the FTO gene, a obese and susceptible gene, found by the whole genome association analysis (GWAS) technique, is the only repeated and successful obesity susceptibility gene in the study of the European population so far. Some domestic studies have also shown that There is a correlation between the FTO gene and the occurrence of obesity. In addition, there have been reports that the FTO gene is associated with the occurrence of T2DM, but the correlation between FTO and diabetes is independent of BMI, and the results are not consistent in the existing related studies. The purpose of this study is to explore the correlation between the rs9939609 locus polymorphism of the FTO gene and diabetes. Methods: a multistage cluster sampling method was used in -8 month of April 2011 to investigate the residents over 40 years old in 3 communities in Luzhou. The physical examination and biochemical tests were conducted in the month of June 2014. The people were followed up in the month of June 2014. The subjects were excluded from the loss of prevention and data, and 500 subjects were selected by the random sampling method (random number table method). Gene locus polymorphism was measured by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP or CAPs). Results: a total of 496 non diabetic subjects were enrolled in this study, including 188 males, 308 females, 311 abdominal circumference, 185 abdominal obesity and A alleles at the rs9939609 locus of 15.3%., which were normal and normal weight of 15.3%.. The frequencies of TA genotypes in the obese group were 20.1%, 31.8%, and AA respectively 1.6%, 3.3% (P0.05).TAAA genotype baseline waistline (Waist circumference, WC), and the BMI index was higher than that of the TT genotype (P0.05). The incidence of TT and TAAA genotypes was 10.1%, 16.7%, respectively, for 3 years. BMI, blood sugar, blood lipid and other effects, the results show that the FTO gene rs9939609 locus A allele is not a risk factor for diabetes in non diabetic population. Conclusion: there is a correlation between the rs9939609 locus of the 1.FTO gene and obesity (defined by BMI). The A allele increases the risk of obesity in the risk of.2. for 3 years, and the incidence of TAAA type diabetes is higher than that of TT type. The risk of genotype diabetes is higher than that of type TT and may be mediated by BMI.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1

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