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Investigation Of Obesity Related Diseases And The Relationship Between PPARγ2, ADPN Gene Polymorphisms And Primary Macroangiopathy In Obesity And Diabetes Mellitus.

Posted on:2007-01-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z H AiFull Text:PDF
GTID:1114360272961322Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objectives(1) To investigate the epidemic situation of diseases such as obesity and related hypertension, hyperlipidemia, hyperglycemia in medical colleges, and explore the relationship between obesity and hypertension, hyperlipidemia, hyperglycemia. (2) To explore the relationship between Pro12Ala polymorphism of PPARγ2 (peroxisome proliferator-activated receptor gamma 2 ) gene, Gly15Gly polymorphism of ADPN ( adiponectin ) gene and obesity in Chinese people. (3) To observe primary prevention of T2DM macrovascular complication through comprehensive intervention on the control of serum glucose, blood pressure, blood lipid and other intervention measures such as treatment with Anti—oxidants vitamin E, traditional Chinese medicine Compound Danshen Drop Pills. (4) To explore the relationship between Pro12Ala polymorphism of PPARγ2 gene, Gly15Gly polymorphism of ADPN gene and T2DM macrovascular complication.Methods1. We investigated the prevalence of obesity, hyperlipidemia, hypertension and hyperglycemia on 1220 officials whose ages were above 20 in the Third Military Medical University and its first affiliated hospital.2. We measured body fat mass(BFM)and body mass index(BMI)with Body Compsition Analyzerce,and detected the genotype of Pro12Ala of PPARγ2 gene and Gly15Gly of ADPN in 116 obesity group and 89 non- obesity group respectively with PCR-RFLP (restriction fragment length polymorphism), then compared the genotype and allele frequency between the two groups. We also measured adiponectin with enzyme-linked immunosorbent assay and Leptin with Radioimmunoassay respectively.3. We applied three-year's comprehensive intervention including the control of blood glucose, blood pressure, blood lipid , and additional treatment with VE capsule (200mg/d), also traditional Chinese medicine Compound Danshen Drop Pills to 176 patients with newly-developed T2DM, then carried out B ultrasound detection of IMT (Intima-media thickness ,IMT ) of common carotid artery. For patients with T2DM primary macrovascular complication, we detected Pro12Ala polymorphism of PPARγ2 and Gly15Gly polymorphism of ADPN respectively.ResultsAmong 1220 school and hospital officials, 301 cases(24.7%) are overweight, 287 cases(23.5%) are Obesity. Overweight rate of male is significantly higher than that of female (31.8% vs 13.7%,p<0.05). Of 287 Obesity cases,249 cases are male,38 are female, obseity rate of male is significantiy more than female (33.7% vs 7.9%,p<0.05). The prevalence of hypertension, hyperlipidemia, hyperglycemia is 28.2%,16.1% and 7.05% respectively , and the prevalence of male is significantly higher than that of female. BMI is predominantly correlated with the level of blood glucose, blood pressure and blood lipid.Plasmic adiponectin level of obesity patients is significantly lower than that of control group(18.07±7.59ug/ml vs 23.99±7.41ug/ml,p<0.05), adiponectin is inversely correlated with HOMA-insulin resistance index(HOMA-IR). A allele frequency of PPARγ2 gene in patients with obesity is significantly higher than that in control group(11.64% vs 5.06%,p<0.05). Compared with the wide isozygote carriers(that is PP genotype), A allele carriers have higher BMI , WC(waist circumstance), BFM and Triglyceride ,but have obviously lower HDL-C( High density lipoprotein cholesterol). There are no significant differences of TT, TG, GG genotype of ADPN gene and allele frequency between the obesity group and control group.After the control of blood glucose, blood pressure, blood lipid by applying three-year's comprehensive intervention and additional treatment with VE capsule (200mg/d) and traditional Chinese medicine Compound Danshen Drop Pills to patients with newly-developed T2DM,of 176 cases,56 developed atherosclerosis (AS)(31.8%). There are no significant differences of incidence rate of AS and IMT value in different treated groups. There are no significant differences of genotype distribution of Pro12Ala polymorphism for PPARγ2 gene and allele frequency between patients with AS and without AS patients. Forthermore, AS patients are more likely to have GG genotype of ADPN gene than the patients without AS(25.0% vs 6.2%,p<0.05). Blood adiponectin in patients with GG genotype(15.10±7.04 ug/ ml) is lower than that in ones with TT genotype (19.64±6.64ug/ml).Conclusions1. Obesity situation isn't optimistic for officials in medical colleges, especially for the male whose overweight prevalence is at a high level. Obesity closely correlates with hypertension, hyperlipidemia, hyperglycemia.2. The decrease of blood adiponectin in obesity patients is relevant to insulin resistance.3. Pro12Ala variation of PPARγ2 gene is relevant to obesity in Chongqing, mutated G allele carrier(PA/AA genotype)is the predisposing genotype. There is no obvious correlation between Gly15Gly genotype polymorphism of ADPN gene and obesity.4. Both middle or small dose of VE and Compound Danshen Drop Pills don't have particular prevention effect on T2DM primary macroangiopathy, so the prevention of primary T2DM still needs combined therapy.5. There is no manifest relationship between Pro12Ala polymorphism of PPARγ2 and T2DM macrovascular complication. Gly15Gly polymorphism of ADPN gene is related with T2DM primary macrovascular complication, so GG genotype is probably the predisposing gene for T2DM primary macrovascular complication.
Keywords/Search Tags:Obesity, Type 2 diabetes mellitus, Peroxisome proliferator-activated receptor gamma 2, Adiponectin, polymorphism, macrovascular complication
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