| Study 1 A comparative study on risks of coronary artery disease,type 2 diabetes mellitus,coronary artery disease and type 2 diabetes mellitus with advancing age.Backgrouds Coronary artery disease(CAD)is a leading worldwide health problem and is often accompanied with type 2 diabetes mellitus(T2DM)which represents a high incidence and prevalence in the elderly patients.Its prevalence is in rapid and progressive rise,due to the increase in average life expectancy,while it is becoming the major causes of morbidity,mortality,and exceptional healthcare costs.Aging is a physiologic factor that has a strong influence on the prevalences of CAD+T2DM,T2DM and CAD.However,studies on the risks of CAD+T2DM,T2DM and CAD in the elderly patients are relatively insufficient.Therefore,we investigated a case-control study and two single case studies to explore the relationship between advancing age and risks of CAD+T2DM,T2DM and CAD and the characteristics of CAD+T2DM,T2DM and CAD patients with advancing age.Methods We enrolled 230 CAD+T2DM,130 T2DM,249 CAD patients and 424 control subjects.The individuals were stratified into three age groups:<60yrs,60-69yrs and?70yrs.Anthropometric parameters and metabolic indices related to body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressured(DBP),uric acid(UA),total cholesterol(TC),triglyceride(TG),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C)and fasting plasma glucose(FPG)were tested.A case control study was conducted to evaluate the relationship between advancing age and risks of CAD+T2DM,T2DM,CAD in different age groups.Two single case studies were conducted to evaluate the characteristics of CAD+T2DM,T2DM and CAD patients with advancing age.Results1.Association of aging and risk of CAD+T2DMAging was independently associated with increased risk of CAD+T2DM.Compared with CAD+T2DM(<60yrs)patients,the risk of CAD+T2DM was increased in 60?69yrs patients(OR=4.14,95%CI:2.60-6.60,P=0.000)and?70yrs patients(OR=11.50,95%CI:7.18-18.42,P=0.000).Patients with advancing age had a 2.78 times higher risk for developing CAD+T2DM.2.Association of aging and risks of metabolic disorders in CAD+T2DM patientsCompared with CAD+T2DM(<60yrs)patients,the risk of hypertension was higher in CAD+T2DM(60?69yrs and?70yrs)patients(P<0.05).3.Association of aging and risk of T2DMCompared with T2DM(<60yrs)patients,the risk of T2DM was increased in?70yrs patients(OR=3.80,95%CI:2.39-6.04,P=0.000).4.Association of aging and risks of metabolic disorders in T2DM patientsCompared with T2DM(<60yrs)patients,there was an increased risk of hypertension and reduced risks of hypercholesterolemia,fasting hypertriglyceridemia,low HDL-C hyperlipidemia and combined dyslipidemia in T2DM(?70yrs)patients(P<0.05).5.Association of aging and risk of CADCompared with CAD(<60yrs)patients,there were no significant differences of the risk of CAD in 60-69yrs and?70yrs patients(P>0.05).6.Association of aging and risks of metabolic disorders in CAD patientsCompared with CAD(<60yrs)patients,there were significant differences in the risks of overweight,hyperuricemia,hypertriglyceridemia and low HDL-C hyperlipidemia in CAD(?70yrs)patients(P<0.05).Conclusions1.Aging was a risk for developing CAD+T2DM.The risk of hypertension was higher in CAD+T2DM patients.2.Aging was a risk for developing T2DM.The risk of hypertension was higher in T2DM patients,while the risk of dyslipidemia was reduced in T2DM patients with advancing age.3.The risk of overweight,hyperuricemia and dyslipidemia was reduced in CAD patients with advancing age.In conclusion,this study indicated that aging had a strong influence on the prevalences of CAD+T2DM and T2DM.It was helpful to put forward some pointful prevention and treatment in elderly patients.Study 2 Association of gene polymorphisms with coronary artery disease and type 2 diabetes mellitus comorbidityBackgrounds The close relationship between type 2 DM(T2DM)and coronary artery disease(CAD)has led to the common soil hypothesis,postulating that both conditions share common genetic and metabolic factors.Type 2 diabetes is a major risk factor for CAD.We hypothesize that T2DM genetic susceptibility variants might be associated with increased risks of CAD+T2DM,T2DM,CAD.Thus,we carried a study to investigate the association of T2DM related genetic polymorphisms with risks of CAD+T2DM,T2DM,CAD,as well as some related metabolic indicators in North Han Chinese.It would provide new pathophysiology clues to the common soil hypothesis.Methods The method included two parts.We tested 21 T2DM related genetic polymorphisms in 12 genes by high resolution melting(HRM)and sanger sequencing.There were significant differences between three SNPs and risk of CAD+T2DM,including hepatocyte nuclear factor 1?(HNFIB)variant rs4430796,cyckin-dependent kinase 5 regulatory subunit associated protein 1-like 1(CDKAL1)variant rs4712524 and coiled-coil-helix-coiled-coil-helix domain containing 2 pseudogene 9(CHCHD9)variant rsl3292136.Then,rs4430796(HNFIB),rs4712524(CDKAL1)and rsl3292136(CHCHD9)polymorphisms were detected in larger sample sizes by HRM and sanger sequencing.The clinical characteristics,biochemical indicators related to body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressured(DBP),uric acid(UA),total cholesterol(TC),triglyceride(TG),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C)and fasting plasma glucose(FPG)were also collected to explore the genotype-phenotype relationship.Results1.rs4430796(HNFIB)There were significant differences in the distribution of genotype frequencies,allele frequencies(OR=1.50,95%CI:1.05-2.13,P=0.026),dominant(OR=1.83,95%CI:1.23-2.72,P=0.003),recessive(OR=2.07,95%CI:1.07-3.98,P=0.027)and additive(OR=2.53,95%CI:1.29-4.98,P=0.006)models between the rs4430796(HNFIB)and CAD+T2DM.CAD+T2DM subjects bearing GG+AG genotype had an increased risk to develop low HDL-C hyperdislipidemia(OR=1.81,95%CI:1.05-3.13,P=0.032).T2DM subjects bearing GG+AG genotype had an increased risk to develop hyperuricemia(OR=3.43,95%CI:1.11-10.55,P=0.025).CAD subjects bearing GG+AG genotype had a reduced risk to develop overweight(OR=0.53,95%CI:0.31-0.90,P=0.019).2.rs4712524(CDKAL1)A significant association between rs4712524(CDKAL1)and CAD in the distribution of recessive model(OR=0.63,95%CI:0.41-0.98,P=0.039)There were significant differences in the distribution of genotype frequencies,dominant(OR=1.59,95%CI:1.05-2.41,P=0.027)and overdominant(OR=1.79,95%CI:1.25?2.56,P=0.001)modles between rs4712524(CDKAL1)and CAD+T2DM.CAD+T2DM subjects bearing GG+AG genotype had a reduced risk to develop overweight(OR=0.39,95%CI:0.19-0.81,P=0.009).T2DM subjects bearing GG+AG genotype had an increased risk to develop high fasting glucose(OR=3.04,95%CI:1.01-9.19,P=0.040).3.rs13292136(CHCHD9)No significant differences in the distribution of allele and genotype frequencies between rsl3292136(CHCHD9)and CAD+T2DM,T2DM,CAD.CAD+T2DM subjects bearing CT genotype had an increased risk to develop high fasting glucose(OR=14.85,95%CI:5.01-44.06,P=0.000).ConclusionsThe results showed that the rs4430796 of HNFIB contributed to susceptibility to CAD+T2DM in the North Han Chinese.The rs4712524 of CDKAL1 contributed to susceptibility to CAD+T2DM,CAD in the North Han Chinese. |
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