A Cohort Study Of The Risk Of Metabolizing Normal Obesity To Diabetes And A Study Of The Relationship Between FTO SNP Rs9939609 And Diabetes

Part one : Diabetes outcomes in the metabolic healthy obese: a prospective cohort studyObjective:With the development of the society and the process of urbanization,people are changing the way of living,in recent decades,the proportion of overweight and obesity in China is significantly increased,as will the prevalence of diabetes also showed a trend of rising year by year.It is well known that obesity is a risk factor for diabetes.In recent years,the previous studies found that the different metabolic state obesity exist differences in incidence of diabetes,known as different sub-types of obesity.Metabolically healthy obese(MHO)phenotype is characterized by obesity and insulin sensitivity.MHO is different from metabolically unhealthy obese(MUHO)phenotype in the morbility risk of type 2 diabetes,cardiovascular diseases,body fat distribution,inflammation level,etc.Due to different defined standards and regional differences,The prevalence of MHO phenotype is different In studies,compared with other obesity subtypes,MHO phenotype increasing the risk of diabetes is still controversial.Our study was to investigate the prevalence of metabolic healthy obese(MHO)phenotype and the prevalence of diabetes of MHO phenotype after followed up for 3 years in the Lu zhou population of over 40 years.Methods:in April 2011 to August,we selected residents over 40 yearsfrom different street community in Lu zhou by multistage cluster sampling method,all subjects accepted questionnaire investigation,physical examination and biochemical tests.All subjects accepted standardized questionnaire,collecting general projects(including name,gender,age,community,etc.),and family history of high blood pressure and diabetes and other basic information.All Participants accepted routine physical examination,including measuring waist circumference,hip circumference,height,weight,resting blood pressure,etc.Questionnaire and physical examination are completed by trained medical graduate students and undergraduate students.Biochemical tests include:fasting blood sugar(FBS),oral glucose tolerance test(OGTT),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C),glycosylated hemoglobin(Hb A1C),etc.Fasting blood specimens require fast at least 8 hours.follow-up survey carried out in June 2014 to October.Follow-up survey content requirements are same as baseline.Results: Eliminated the subjects lost to follow-up and information was not complete,2442 subjects without diabetes were in our study(30.7%men,749 cases),The average age was 59.56±9.57,1693 cases were women with an average age of 56.36±9.02,P < 0.001,the difference is statistically significant.14.8% of total subjects were MHO,with 11.2%of men and 15.4% of women,45.3% of total subjects were metabolichealthy non-obese(MHNO),19.5% were metabolic unhealthy obese(MUHO)and 45.3% were metabolic unhealthy non-obese(MUHNO).Stratified analysis according to age,MHO morbidity rates of40-45 years old,56-70 years old,more than 70-years old were 14.8%,14.3% and 9.6% respectively.Over the median follow-up of 3 years,there were 248 cases development into type 2 diabetes.Compared with MHNO individuals,the other phenotype were at increased risk for type 2diabetes,MHO(OR=1.64,95% CI,0.99 ~ 2.70),MUHO(OR=5.23,95%CI,3.72 ~ 7.36),MUHNO(OR=3.93,95% CI,2.74 ~ 5.64),women in MHO(OR=2.05,95% CI,1.15 ~ 3.65).By gender stratification analysis,diabetes risk of MHO,MUHO,MUHNO in male 0.88,3.53,2.53 times respectively compared with MHNO,while women were 2.05,6.23,4.85 times respectively.Over 3 years follow-up,the abnormal index percentage of MHO including triglyceride(TG),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood sugar(FBS),OGTT2 h glucose were 34.3%,39.4%,22.6%,8.3%,22.6% respectively,increased significantly compared with MHNO(p < 0.05).Conclusion: 1.The prevalence of MHO among women and relatively young people is higher.2.The prevalence of MHO diabetes incidence was lower than MUHO and MUHNO,MHO of women diabetes incidence was higher than MHNO.3.Compared with MHNO,MHO metabolic abnormalities were more likely to happen.Part two : The relationship between FTO SNP rs9939609 and diabetes mellitus :a prospective cohort studyObjective: The FTO gene was a Gene associated with obesity founded by Genome-wide association study(GWAS).In Europe,the FTO gene(Fat mass and obesity associated gene)had been confirmed with BMI(Body mass Index)repeatedly and successfully,Some domestic studies had also shown the FTO gene associated with obesity.In addition,The previous studies had reported that the FTO gene associated with the occurrence of T2 DM,but whether FTO gene was relevant to diabetes independent of BMI was still inconsistent in the previous related research.Our study was to investigate the relationship between FTO gene rs9939609 polymorphism and diabetes mellitus.Methods: In April to August 2011,we selected adults over 40 years from 3 different street community in Lu zhou,Si Chuan,China by multistage cluster sampling method,all subjects accepted questionnaire investigation,physical examination and biochemical tests.In June to October 2014,we did follow-up survey.Eliminated the subjects lost to follow-up and information was not complete,extract 500 cases of the subjects using the method of simple random sampling method(The stochastic indicatormethod).Application of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method for determining gene loci polymorphism.Results: A total of 496 subjects,among which 188 cases were male,308 cases were female,204 cases of normal weight,218 cases of overweight,74 cases of obesity.The allele frequency of A of rs9939609 in all cases was 15.3%.Normal weight and obese TA genotype frequency were 20.1%,31.8% respectively.AA type were 1.6% and 1.6%respectively(P < 0.05).Baseline WC,BMI index of TA&AA genotype were higher than TT genotype(P<0.05).Follow-up of 3 years,TT and TA&AA genotype diabetes rates were 10.1%,16.7% respectively,p=0.042,OR=1.789,95% CI(1.017~ 1.017).Logistic regression analysis,after adjustment for BMI,blood glucose,blood lipid,etc,the results showed FTO gene rs9939609 A allele was not a risk factor for diabetes.Conclusion: 1.Our study found that FTO gene rs9939609 correlated with obesity(BMI defined),A allele increased the risk of obesity.2.Diabetes morbidity rates of TA&AA was higher than TT type,it may be associated with BMI mediated.