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代謝正常肥胖轉(zhuǎn)歸糖尿病風(fēng)險的隊(duì)列研究及FTO SNP rs9939609與糖尿病關(guān)系的研究

發(fā)布時間:2018-06-18 17:33

  本文選題:肥胖 + 代謝正常肥胖(MHO)。 參考:《西南醫(yī)科大學(xué)》2017年碩士論文


【摘要】:第一部分代謝正常肥胖轉(zhuǎn)歸糖尿病風(fēng)險的前瞻性隊(duì)列研究背景和目的:隨著社會的發(fā)展,城市化的進(jìn)程,人們正活方式的改變,近幾十年,我國超重和肥胖的比例明顯的增加,糖尿病患病率也呈逐年上升的趨勢。眾所周知,肥胖是糖尿病的危險因素。近年研究發(fā)現(xiàn)不同代謝狀態(tài)的肥胖人群在糖尿病發(fā)病率上存在差異,稱為肥胖的不同亞型。代謝正常肥胖(MHO)以肥胖但胰島素敏感為特征,與代謝異常肥胖(MUHO)在2型糖尿病、心血管疾病等發(fā)病風(fēng)險、體脂分布、炎癥水平等方面存在差異。MHO患病率在不同研究中因界定標(biāo)準(zhǔn)及地區(qū)等不同結(jié)果差異較大,與其他肥胖亞型相比,MHO是否增加糖尿病發(fā)病風(fēng)險尚存在爭議。本文旨在了解瀘州社區(qū)40歲以上代謝正常肥胖(MHO)患病率及隨訪3年糖尿病發(fā)病率情況。研究對象和方法:2011年4月-8月采用多級整群抽樣方法,對瀘州市3個社區(qū)不同街道40歲以上居民進(jìn)行問卷調(diào)查、體格檢查、生化檢測等,所有研究對象均進(jìn)行標(biāo)準(zhǔn)化問卷調(diào)查,收集一般情況(姓名、性別、年齡、社區(qū)等),既往高血壓、糖尿病家族史等基本信息。受試者均接受常規(guī)體格檢查,包括測量腰圍、臀圍、身高、體重、靜息時血壓等。問卷調(diào)查的填寫和體格檢查均由經(jīng)過培訓(xùn)的醫(yī)學(xué)研究生及本科生完成。生化檢測內(nèi)容包括:空腹血糖(FBS)、OGTT(口服葡萄糖耐量試驗(yàn))2h血糖、甘油三酯(TG)、總膽固醇(TC)、高密度脂蛋白膽固醇(HDL-C)和低密度脂蛋白膽固醇(LDL-C)、糖化血紅蛋白(Hb A1C)等?崭寡獦(biāo)本要求禁食至少8h。于2014年6月-10月對其進(jìn)行隨訪調(diào)查,隨訪調(diào)查內(nèi)容及要求同基線。結(jié)果:排除失訪及資料不全者,本調(diào)查共計納入2442例非糖尿病人群(其中男性749例,占比30.7%),平均年齡59.56±9.57,女性1693例,平均年齡56.36±9.02,P0.001,差異具有統(tǒng)計學(xué)意義。MHO、代謝正常非肥胖(MHNO)、代謝異常肥胖(MUHO)、代謝異常非肥胖(MUHNO)分別占比14.8%、45.3%、19.5%、20.4%,男、女MHO患病率分別為11.2%、15.4%。按年齡分層分析,結(jié)果顯示40-45歲、56-70歲、70歲以上人群MHO患病率分別為14.8%、14.3%、9.6%。隨訪3年,共計248例轉(zhuǎn)歸為糖尿病,與MHNO相比,MHO、MUHO、MUHNO糖尿病發(fā)病風(fēng)險分別是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糖尿病發(fā)病風(fēng)險是MHNO的2.05(95%CI,1.15~3.65)倍。按性別分層分析,男性MHO、MUHO、MUHNO糖尿病發(fā)病風(fēng)險分別是MHNO的0.88、3.53、2.53倍,女性分別是2.05、6.23、4.85倍。MHO組隨訪3年后甘油三酯(TG)、收縮壓(SBP)、舒張壓(DBP)、空腹血糖(FBS)、OGTT2h血糖指標(biāo)異常百分比分別為34.3%、39.4%、22.6%、8.3%、43.4%,與MHNO組相比明顯增加(p0.05)。結(jié)論:1.MHO在女性和相對低齡的人群中患病率更高。2.MHO組糖尿病發(fā)病率明顯低于MUHO、MUHNO組,女性MHO組糖尿病發(fā)病率高于MHNO組。3.與MHNO相比,MHO更易發(fā)生代謝異常。第二部分FTO SNP rs9939609與糖尿病關(guān)系的前瞻性隊(duì)列研究背景和目的:FTO基因是通過全基因組關(guān)聯(lián)分析(GWAS)技術(shù)發(fā)現(xiàn)的一個肥胖易感基因。FTO基因是到目前為止在歐洲人群的研究中唯一多次重復(fù)并且成功的肥胖易感基因。國內(nèi)一些研究也表明FTO基因與肥胖的發(fā)生具有相關(guān)性。此外,有研究報道稱FTO基因與T2DM的發(fā)生相關(guān),但FTO與糖尿病的相關(guān)性是否獨(dú)立于BMI而存在,在現(xiàn)有的相關(guān)研究中,結(jié)果并不一致。本文旨在探討FTO基因rs9939609位點(diǎn)多態(tài)性與糖尿病的相關(guān)性。研究對象和方法:2011年4月-8月采用多級整群抽樣方法,對瀘州市3個社區(qū)不同街道40歲以上居民進(jìn)行問卷調(diào)查、體格檢查、生化檢測,于2014年6月-10月對其進(jìn)行隨訪調(diào)查。排除失防及資料不全者,采用簡單隨機(jī)抽樣的方法(隨機(jī)數(shù)表法)抽取500例受試者,應(yīng)用聚合酶鏈反應(yīng)-限制性片段長度多態(tài)性(PCR-RFLP或CAPs)的方法測定基因位點(diǎn)多態(tài)性。結(jié)果:共計納入496例非糖尿病受試者,其中男性188例,女性308例,腹圍正常311例,腹型肥胖185例。FTO基因rs9939609位點(diǎn)A等位基因分布頻率為15.3%。正常體重和肥胖組TA基因型頻率分別為20.1%、31.8%,AA型分別為1.6%、3.3%(P0.05)。TAAA基因型基線腰圍(Waist circumference,WC)、BMI指標(biāo)值較TT基因型升高(P0.05)。隨訪3年,TT和TAAA基因型糖尿病發(fā)病率分別為10.1%、16.7%,p=0.042,OR=1.789,95%CI(1.017~3.147)。Logistic回歸分析,校正BMI、血糖、血脂等影響后,結(jié)果顯示FTO基因rs9939609位點(diǎn)A等位基因不是非糖尿病人群轉(zhuǎn)歸糖尿病的危險因素。結(jié)論:1.FTO基因rs9939609位點(diǎn)與肥胖(以BMI界定)存在相關(guān)性,A等位基因增加肥胖患病風(fēng)險。2.隨訪3年,TAAA型糖尿病發(fā)病率較TT型高。AATA基因型糖尿病發(fā)病風(fēng)險高于TT型可能與BMI介導(dǎo)相關(guān)。
[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.
【學(xué)位授予單位】:西南醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R587.1

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