肥胖相关疾病调查及PPARγ2、ADPN基因多态性与肥胖、糖尿病早期大血管病变关系的研究
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摘要
目的:
研究肥胖及其相关的高血压、高血脂、高血糖等疾病在医学院校的流行现状,探讨肥胖与高血脂、高血压、高血糖的关系;探讨PPARγ2基因Pro12Ala多态性、脂联素Gly15Gly多态性与中国人群肥胖的关系;观察强化血糖、血压、血脂控制及不同干预措施,包括抗氧化剂维生素E、传统中药复方丹参滴丸对2型糖尿病(T2DM)大血管并发症的一级预防作用;探讨PPARγ2基因Pro12Ala多态性、脂联素基因Gly15Gly多态性与T2DM大血管并发症的关系。
方法:
1.调查某医学院及附属医院1220名年龄20岁以上干部的肥胖、高血脂、高血压、高血糖的发生情况。
2.用体脂分析仪测定体脂含量(BFM)和体重指数(BMI),采用聚合酶链反应-限制性片段长度多态法(PCR-RFLP),检测116名肥胖组和89名非肥胖对照组PPARγ基因Pro12Ala、脂联素基因Gly15Gly基因型,比较两组基因型和等位基因频率。酶联免疫法检测血浆脂联素。
3.对176名新发生的T2DM患者进行3年的强化血糖、血压、血脂控制及加用抗氧化剂维生素E、传统中药复方丹参滴丸治疗,高分辨彩色B超检测颈总动脉内膜中层(IMT)厚度。检测2型糖尿病早期大血管并发症患者PPARγ2基因Pro12Ala多态性、脂联素Gly15Gly多态性。
结果:
1220名学校和医院干部中,301例(24.7%)超重,287例肥胖(23.5%)。男性超重率显著高于女性(31.8% vs 13.7%,p<0.05);287例肥胖者中,男性249例,女性38例,男性肥胖患病率显著高于女性(33.7% vs 7.9%,p<0.05);高血脂、高血压、高血糖患病数分别为344例(28.2%)、195例(16.1%)和85例(7.05%)。BMI和血压、血脂、血糖水平显著相关。
肥胖患者血浆脂联素(18.07±7.59ug/ml)显著低于对照组(23.99±7.41ug/ml),脂联素与HOMA胰岛素抵抗指数(HOMA-IR)负相关。肥胖患者PPARγ2基因A等位基因频率,显著多于对照组(11.64%vs5.06%,p<0.05)。A等位基因携带者的BMI、腰围、BFM、甘油三酯显著高于无突变的野生纯合子,而HDL-C显著低于PP组。肥胖组和对照组的脂联素基因TT、TG、GG基因型分布、等位基因频率无显著差异,肥胖组G等位基因携带者血浆脂联素明显降低。
176例新发T2DM分别经过3年强化血糖、血压、血脂控制及加用维生素E、复方丹参滴丸治疗,共发生动脉粥样硬化(AS)56例(31.8%),各治疗组AS发生率无显著差别,IMT值无显著差别。56例T2DM早期大血管病变组PPARγ2基因Pro12Ala多态性的基因型分布、等位基因频率无显著差异。T2DM AS病变组脂联素基因GG基因型(25.0%)显著高于无AS者(6.2%),GG基因型的血脂联素水平(15.10±7.04 ug/ ml)显著低于TT基因型者(19.64±6.64ug/ml,P<0.05)。
结论:
1.医学院校干部超重肥胖情况不容乐观,尤其男性的超重肥胖患病率在比较高的水平;肥胖与高血脂、高血压、高血糖的发生紧密相关。
2.肥胖患者血脂联素水平下降,与胰岛素抵抗有关。
3.重庆地区人群PPARγ2基因Pro12Ala变异与肥胖的发生有关,突变G等位基因携带者(PA/AA基因型)是肥胖的易感基因型。脂联素基因Gly15Gly多态性与肥胖无明显关系。
4.中小剂量VE、复方丹参滴丸,没有表现出独特的对T2DM早期大血管病变的预防作用,T2DM大血管并发症的一级预防,仍需综合治疗。
5.PPARγ2 Pro12Ala多态性与T2DM大血管并发症的发生无明显关系;脂联素基因Gly15Gly多态性与2型DM大血管并发症有关,GG基因型可能通过影响血浆脂联素水平,促进AS的发生,GG基因型是2型糖尿病大血管并发症的易感基因型。
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.
Methods
1. 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.
Results
Among 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).
Conclusions
1. 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.
研究肥胖及其相关的高血压、高血脂、高血糖等疾病在医学院校的流行现状,探讨肥胖与高血脂、高血压、高血糖的关系;探讨PPARγ2基因Pro12Ala多态性、脂联素Gly15Gly多态性与中国人群肥胖的关系;观察强化血糖、血压、血脂控制及不同干预措施,包括抗氧化剂维生素E、传统中药复方丹参滴丸对2型糖尿病(T2DM)大血管并发症的一级预防作用;探讨PPARγ2基因Pro12Ala多态性、脂联素基因Gly15Gly多态性与T2DM大血管并发症的关系。
方法:
1.调查某医学院及附属医院1220名年龄20岁以上干部的肥胖、高血脂、高血压、高血糖的发生情况。
2.用体脂分析仪测定体脂含量(BFM)和体重指数(BMI),采用聚合酶链反应-限制性片段长度多态法(PCR-RFLP),检测116名肥胖组和89名非肥胖对照组PPARγ基因Pro12Ala、脂联素基因Gly15Gly基因型,比较两组基因型和等位基因频率。酶联免疫法检测血浆脂联素。
3.对176名新发生的T2DM患者进行3年的强化血糖、血压、血脂控制及加用抗氧化剂维生素E、传统中药复方丹参滴丸治疗,高分辨彩色B超检测颈总动脉内膜中层(IMT)厚度。检测2型糖尿病早期大血管并发症患者PPARγ2基因Pro12Ala多态性、脂联素Gly15Gly多态性。
结果:
1220名学校和医院干部中,301例(24.7%)超重,287例肥胖(23.5%)。男性超重率显著高于女性(31.8% vs 13.7%,p<0.05);287例肥胖者中,男性249例,女性38例,男性肥胖患病率显著高于女性(33.7% vs 7.9%,p<0.05);高血脂、高血压、高血糖患病数分别为344例(28.2%)、195例(16.1%)和85例(7.05%)。BMI和血压、血脂、血糖水平显著相关。
肥胖患者血浆脂联素(18.07±7.59ug/ml)显著低于对照组(23.99±7.41ug/ml),脂联素与HOMA胰岛素抵抗指数(HOMA-IR)负相关。肥胖患者PPARγ2基因A等位基因频率,显著多于对照组(11.64%vs5.06%,p<0.05)。A等位基因携带者的BMI、腰围、BFM、甘油三酯显著高于无突变的野生纯合子,而HDL-C显著低于PP组。肥胖组和对照组的脂联素基因TT、TG、GG基因型分布、等位基因频率无显著差异,肥胖组G等位基因携带者血浆脂联素明显降低。
176例新发T2DM分别经过3年强化血糖、血压、血脂控制及加用维生素E、复方丹参滴丸治疗,共发生动脉粥样硬化(AS)56例(31.8%),各治疗组AS发生率无显著差别,IMT值无显著差别。56例T2DM早期大血管病变组PPARγ2基因Pro12Ala多态性的基因型分布、等位基因频率无显著差异。T2DM AS病变组脂联素基因GG基因型(25.0%)显著高于无AS者(6.2%),GG基因型的血脂联素水平(15.10±7.04 ug/ ml)显著低于TT基因型者(19.64±6.64ug/ml,P<0.05)。
结论:
1.医学院校干部超重肥胖情况不容乐观,尤其男性的超重肥胖患病率在比较高的水平;肥胖与高血脂、高血压、高血糖的发生紧密相关。
2.肥胖患者血脂联素水平下降,与胰岛素抵抗有关。
3.重庆地区人群PPARγ2基因Pro12Ala变异与肥胖的发生有关,突变G等位基因携带者(PA/AA基因型)是肥胖的易感基因型。脂联素基因Gly15Gly多态性与肥胖无明显关系。
4.中小剂量VE、复方丹参滴丸,没有表现出独特的对T2DM早期大血管病变的预防作用,T2DM大血管并发症的一级预防,仍需综合治疗。
5.PPARγ2 Pro12Ala多态性与T2DM大血管并发症的发生无明显关系;脂联素基因Gly15Gly多态性与2型DM大血管并发症有关,GG基因型可能通过影响血浆脂联素水平,促进AS的发生,GG基因型是2型糖尿病大血管并发症的易感基因型。
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.
Methods
1. 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.
Results
Among 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).
Conclusions
1. 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.
引文
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