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Correlation Between Drinking,PRDM16 And UCP1 Gene Polymorphisms And Microvascular Complications Of Diabetes

Posted on:2021-05-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:P ZhaoFull Text:PDF
GTID:1484306032981589Subject:Internal Medicine
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PART ? Relationship between drinking alcohol and microvascular complications in diabetic patients in GuangxiObjective:1.Investigate the blood glucose and diabetic microvascular complications of diabetic patients in Guangxi.2.Investigate the drinking situation of diabetic patients in Guangxi,and clarify the relationship between drinking and diabetic microangiopathy.Methods:Four monitoring points are randomly selected from the Guangxi chronic disease monitoring system,and each monitoring point is randomly selected from four areas.Diabetes patients aged between 18 and 80 years old who lived in the survey area for more than 6 months in the past 1 year were selected as the research subjects.Register the general situation of the research subjects,measure the physical indicators,detect fasting blood glucose(Fasting Blood Glucose,FBG),glycosylated hemoglobin A1C(Hb A1c),urine albumin/creatinine ratio(Abumin to Creatinine Ratio,ACR);The subjects underwent fundus photography and screening for neuropathy such as vibration sensation and pain temperature sensation.Compliance standard: Hb A1C:Hb A1C<7%;FBG: FBG is between 4.4 mmol/L and 7 mmol/L.Alcohol consumption refers to alcoholic drinks ?1 times and drinking ?1 standard drinking unit(equal to 10 g pure ethanol)within 1 year before the survey,otherwise it is regarded as non-drinkers.Drinking degree classification: light drinking: drinking volume ? 2 standard drinking units/day(regardless of men and women);moderate drinking: between light and heavy drinking;heavy drinking: female drinking volume ? 4 standard drinking units/day,male Drinking volume ? 6 standard drinking units/day.Drinkers are classified according to frequency of drinking.Occasionally drinking: No drinking phenomenon within 1 month before the survey of drinkers;Regular drinking:Drinking phenomenon within 1 month before the survey of drinkers.To investigate the drinking,blood sugar and diabetic microvascular complications of diabetic patients in Guangxi,and to determine the relationship between alcohol consumption and microvascular complications of diabetic patients in Guangxi.Results:1.Blood glucose compliance and diabetic microvascular complications in diabetic patients in GuangxiThis study analyzed data from 1673 diabetic patients.The average value of Hb A1 c is 7.8%±2.2%,with Hb A1c<7.0% as the standard of compliance,745cases(44.5%)of those who met the standard,and 928 cases(55.5%)of those who did not meet the standard;the average value of FBG was 9.1 mmol/L±3.8mmol/ L,with the FBG value between 4.4mmol/L and 7.0mmol/L as the standard of compliance,577 cases(34.5%)of the standard,1096 cases(65.5%)of the standard;? 4.4mmol/L of the standard 8 cases(0.7%),1088 cases(99.3%)with ?7mmol/L.235 patients(14.0%)in Diabetic peripheral neuropathy(DPN)group,including 85 patients(36.2%)who achieved Hb A1 c,150 patients(63.8%)who did not meet the standard;1438 patients who were not DPN(86.0%),among which 660(45.9%)achieved Hb A1 c and 778(54.1%)did not meet the standard.There was a significant difference in the Hb A1 c compliance rate between the DPN group and the non-DPN group(?2=7.373,P<0.01).99 patients(5.9%)in the Diabetic kidney disease(DKD)group,including 24 patients(24.2%)who achieved the Hb A1 c standard,75 patients(75.8%)who did not meet the standard;1574 patients(94.1%)who were not DKD,Among them,721 cases(45.8%)achieved Hb A1 c and 853 cases(54.2%)did not meet the standard.There were significant differences in the Hb A1 c compliance rate between the DKD group and the non-DKD group(?2=17.535,P<0.01);182 cases(10.9 %)In patients with diabetic retinopathy(DR),52 patients(28.6%)achieved Hb A1 c and 130 patients(71.4%)failed;1491(89.1%)non-DR patients,including There were 693 cases(46.5%)of those who achieved Hb A1 c,and 798 cases(53.5%)that did not meet the criterion.There was a significant difference in the Hb A1 c compliance rate between the DR group and the non-DR group(?2=21.058,P<0.01).There were 373 patients(22.3%)in the microvascular complications group(DPN/DKD/DR),128 patients(34.3%)achieved Hb A1 c,245 patients(65.7%)failed,and 1300 patients with non-microvascular disease,Hb A1 c There were 617 cases(47.5%)who met the standard and 683 cases(52.5%)who did not meet the standard.There was a significant difference in the Hb A1 c compliance rate between the microvascular disease group and the non-microvascular disease group(?2=20.276,P<0.01).Among the 235 patients in the DPN group,65(27.7%)achieved FBG,170(72.3%)failed,and 1438 non-DPN patients,including 512(35.6%)FBG and926(none)64.4%),there was a significant difference in the FBG compliance rate between the two groups(?2=5.644,P<0.05);99 patients in the DKD group,including 20 patients(20.2%)who achieved the FBG standard and 79 patients(79.8%)who did not meet the standard,1574 Among the non-DKD patients,557(35.4%)achieved FBG and 1017(64.6%)did not meet the standard.There was a significant difference in the FBG compliance rate between the two groups(?2=9.506,P<0.01);182 patients in the DR group,Among them,38 cases(20.9%)achieved FBG,144 cases(79.1%)failed,1491 non-DR patients,539cases(36.2%)achieved FBG,952 cases(63.8%)failed,two There were significant differences in FBG compliance rate between groups(?2=16.742,P<0.01);373 patients with microvascular complications(DPN/DKD/DR),including 93 patients(24.9%)who achieved FBG and 280 patients who failed(75.1%),1300 patients with non-microvascular complications,including 484patients(37.2%)who achieved the FBG standard and 816 patients(62.8%)who did not meet the standard.There was a significant difference in the FBG compliance rate between the two groups(?2=19.401,P< 0.01).2.Drinking alcohol in Guangxi diabetic patients and its relationship with diabetic microangiopathy1673 cases of patients with diabetes in Guangxi: 823 males(49.2%),850females(50.8%);1171 Han nationality(70.0%),502 minority nationalities(30.0%).353 drinkers(21.1% of the total population),237 Han people(20.2%of the total Han population),116 ethnic minorities(23.1% of the total minority population),and 308 male drinkers(37.4% of the total male population)%),45 female drinkers(5.3% of the total number of women).Of the 353 diabetic patients who drink alcohol in Guangxi,228(64.6%)diabetic patients with mild drinking,70(19.8%)diabetic patients with moderate drinking,and 55(15.6%)diabetic patients with heavy drinking.According to the frequency of drinking,there were 32 occasional drinkers(9.1%)and 321 regular drinkers(90.9%).Moderate drinking compared to no drinking is a risk factor for DPN in diabetic patients.After adjusting for age,disease duration,body mass index(BMI),waist circumference(Waist Circumference,WC),systolic blood pressure(SBP),FBG,Hb A1 c,and ACR covariates,multivariate unconditional logistic regression analysis: For patients with diabetes in Guangxi,the odds ratio(OR)of DPN risk for moderate drinkers compared with no drinkers was 1.968,95%confidence interval(CI): 1.099-3.524(P<0.05),light,Severe drinking is not related to DPN risk(P>0.05).Severe drinking increased the risk of DR in patients with diabetes in Guangxi compared with no drinking.After adjusting the pulse,course,SBP,FBG,Hb A1 c and ACR covariates,the results of the multivariate unconditional logistic regression model: patients with diabetes in Guangxi,heavy drinkers had a DR risk OR of 2.192,95%CI: 1.078-4.458(P<0.05),there was no statistically significant difference in the risk of DR between light and moderate drinkers compared with no drinkers(P>0.05).Compared with non-drinkers,there was no significant difference in the risk of DR and DPN among diabetic patients in Guangxi(P>0.05);there was no significant difference in the risk of DR and DPN among diabetic drinkers of different drinking frequency compared with non-drinkers(P>0.05).Alcohol consumption is not associated with the risk of DKD in patients with diabetes in Guangxi(P>0.05).Conclusions:1.The compliance rate of Hb A1 c in patients with diabetes in Guangxi is only 44.5%,and the compliance rate of FBG is 34.5%.2.The prevalence of DPN in patients with diabetes in Guangxi was 14.0%;the prevalence of DR was 10.9%,and the prevalence of DKD was 5.9%.3.Drinking has nothing to do with DKD in patients with diabetes in Guangxi.Moderate drinking leads to an increased risk of DPN in patients with diabetes in Guangxi,while heavy drinking leads to an increased risk of DR in patients with diabetes in Guangxi.PART ? Relationship between polymorphism of PRDM16 and UCP1 genes and diabetic microangiopathyObjective:1.To explore the relationship between PRDM16 and UCP1 gene polymorphisms and microvascular complications in diabetic patients in Guangxi.2.To understand whether the interaction between PRDM16,UCP1 gene locus and environmental factors such as drinking is involved in the process of microangiopathy in diabetic patients in Guangxi.Methods:This part of the study uses a matched case control method,with the help of SPSS19.0 software,to match the DPN group and the control group without DPN to the first part of the study subjects by age(±3 years)and gender 1:1.After matching,the general situation of the research object,biochemical results and other data are taken from the first part of the study.In the first part of the study,each research subject collected 2ml of peripheral blood with an EDTA tube,labeled the number,transported it in time and stored it in a low temperature refrigerator,and extracted DNA using the kit method.The multiplex SNa Pshot method was used to detect the polymorphism of PR domain containing 16(PRDM16)gene rs2236518,rs870171 and uncoupling protein 1(UCP1)gene rs1800592,rs3811791,rs10011540,rs45539933.To explore the relationship between genetic polymorphisms of PRDM16 and UCP1,the interaction of genes and alcohol,and the genetic susceptibility to microangiopathy in diabetic patients in Guangxi.SPSS19.0 software was used to analyze the single factor and multifactorial risk of diabetic microangiopathy.The relationship between DPN risk factors,genotype of each gene locus and DPN in diabetic patients was analyzed by conditional logistic regression.Multi-factor unconditional logistic regression was used to analyze the relationship between DR,DKD risk factors,genotypes of various loci and disease in diabetic patients.SHEsis software analyzes Hardy-Weinberg equilibrium,linkage disequilibrium,and haplotypes between sites.Using MDR software and SPSS19.0 software Logistic regression to analyze the interaction between susceptible genes and alcohol and other environmental factors on diabetic microangiopathy.Results:1.Diabetic microangiopathy and PRDM16 and UCP1 gene loci in the study subjectsAmong the 1673 subjects,235 in the DPN group and 1438 in the control group without DPN.After 1:1 matching based on age(±3 years)and gender factors,a total of 456 patients(228 pairs of DPN group and control group)were matched.Perform genetic polymorphism analysis.Among the 456 patients with diabetes in Guangxi,there were 99 patients(21.7%)in the DR group and 357patients(78.3%)in the control group without DR;56 patients(12.3%)in the DKD group among the 456 patients with diabetes in Guangxi The number of diabetic patients in the control group of DKD was 400(87.7%).Among the 456 subjects,270 were Han(59.2%)and 186 were minority(40.8%).Among the 186 minority patients,176 were Zhuang(94.6%),8 were Yao(4.3%),and 2 were Miao(1.1%).Using SPSS software analysis,the genotype distribution frequencies of UCP1 loci rs1800592,rs10011540,rs45539933,rs3811791 and PRDM16 loci rs2236518,rs870171 were not significantly different between Han and ethnic minorities(P>0.05).One genotype CC was detected at rs3811791 locus;three genotypes were detected at rs1800592,rs10011540,rs45539933 and PRDM16 loci rs2236518 and rs870171 in UCP1 loci.SHEsis software analysis found that only the rs1800592 and rs870171 two sites in each case group and the corresponding control group were consistent with the group representative(P>0.05).2.PRDM16 and UCP1 gene polymorphism and diabetic peripheral neuropathyCompared with heterozygous GA after adjusting the factors of disease course,FBG,ethnicity,Hb A1 c,and drinking degree in conditional logistic regression analysis,compared with heterozygous GA,homozygous GG at rs1800592 is a protective genotype to prevent DPN in patients with diabetes in Guangxi,with an OR of 0.565(95%CI: 0.340-0.940,P<0.05);compared with GA+AA genotype,homozygous GG at rs1800592 is still a protective genotype to prevent DPN in Guangxi diabetic patients,OR is 0.544(95%CI: 0.336-0.880,P<0.05);compared with GA genotype,AA+GG genotype at rs1800592 is not associated with DPN risk in diabetic patients(P>0.05).Preliminary analysis,compared with allele A,rs1800592 allele G is a protective factor of DPN,OR is0.794(95%CI: 0.642-0.984,P<0.05);adjust ethnicity,disease course,FBG,Hb A1 c,drinking degree factors After comparison,rs1800592 allele G was compared with A.Carrying allele G was not associated with DPN risk,OR was0.828(95%CI: 0.664-1.032,P>0.05).Before and after adjusting the influencing factors of disease course,ethnicity,FBG,Hb A1 c and alcohol consumption,the polymorphism of PRDM16 gene rs870171 gene in diabetic patients was not related to the risk of DPN(P>0.05).3.PRDM16 and UCP1 gene polymorphism and diabetic retinopathyAfter adjusting for FBG,disease course,Hb A1 c,and ACR factors in multifactorial unconditional logistic regression analysis,compared with patients with GA+AA genotype,patients with GG genotype diabetes at rs1800592 had an increased risk of DR,OR was 1.912(95%CI: 1.141-3.202,P<0.05);after adjusting the disease course,FBG,Hb A1 c,ACR factors,the genotype of rs1800592 locus of UCP1 gene,compared with heterozygous GA,homozygous GG,AA,GG+AA is not DR in patients with diabetes The main influencing factors(P>0.05);rs1800592 allele G compared with A,diabetes patients with allele G increased the risk of DR,after adjusting the course,FBG,Hb A1 c,ACR factors,OR was 1.545(95% CI: 1.111-2.150,P<0.05).The polymorphism of rs870171 in PRDM16 gene is not associated with DR risk in diabetic patients(P>0.05).4.PRDM16 and UCP1 gene polymorphism and diabetic kidney diseaseAfter adjusting the course,pulse,FBG,Hb A1 c,ACR factors in multifactorial unconditional logistic regression analysis,the genotypes of rs1800592 locus of UCP1 gene were not related to the risk of DKD in diabetic patients(P>0.05);rs1800592 allele G was compared with A,The risk of DKD in diabetic patients with allele G was reduced.After adjusting the course,pulse,FBG,Hb A1 c,and ACR factors,the OR was 0.640(95%CI: 0.416-0.985,P<0.05).The polymorphism of the rs870171 locus of PRDM16 gene is not related to the risk of DKD in diabetic patients(P>0.05).5.The interaction between rs1800592 polymorphism of UCP1 gene and environmentAccording to the MDR software analysis,the optimal interaction model between UCP1 gene rs1800592 and ethnicity and drinking degree was formed,which significantly increased the risk of DPN in patients with diabetes in Guangxi(OR: 2.696,95%CI: 1.809-4.019,P<0.01).Conditional logistic regression validated the model: rs1800592(GG)is a protective factor for DPN in diabetic patients;moderate drinking and Han characteristics are a risk factor for DPN in diabetic patients.Through MDR software and multi-factor unconditional logistic regression joint verification,the optimal interaction model between UCP1 gene rs1800592 and disease course and ACR forms a significant increase in the risk of DR in patients with diabetes in Guangxi(OR: 3.733,95%CI: 2.286-6.100,P<0.01).Multi-factor unconditional logistic regression validated the model: rs1800592(GG),disease course,and ACR are risk factors for DR in diabetic patients.Conclusions:1.UCP1 gene locus rs1800592 homozygous GG is a protective genotype for preventing DPN in Guangxi diabetic patients,and is a genotype that increases the risk of DR in Guangxi diabetic patients.UCP1 locus rs1800592 allele G increased the risk of DR in patients with diabetes in Guangxi and reduced the risk of DKD in patients with diabetes in Guangxi.2.The rs1800592 genotype of UCP1 gene locus is not related to the risk ofDKD in patients with diabetes in Guangxi.3.The rs870171 polymorphism of PRDM16 gene is not associated with the risk of diabetic microangiopathy in diabetic patients in Guangxi.4.There is an interaction between the GG genotype,ethnicity and drinking level of the UCP1 gene rs1800592,which is closely related to the occurrence of DPN in diabetic patients in Guangxi;there is an interaction between the GG genotype,disease course and ACR of the rs1800592 locus of the UCP1 gene,and Guangxi The occurrence of DR in diabetics is closely related.
Keywords/Search Tags:Drinking, Diabetic peripheral neuropathy, Glycated hemoglobin, Diabetic kidney disease, Diabetic retinopathy, UCP1, PRDM16, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy
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