PGC-1α与胰岛素抵抗

过氧化物酶体增生物激活受体γ共激活因子1α（PGC-1 α）,是一种核转录共激活因子,它与不同的转录因子结合发挥不同的功能。PGC-1 α在胰岛素抵抗和2型糖尿病人群的表达下降。环境和遗传因素均可影响PGC-1 α的表达,高脂使PGC-1 α表达下降,降低胰岛素敏感性,而运动可增加PGC-1 α表达,改善胰岛素抵抗。PGC-1 α的基因多态性与胰岛素抵抗、2型糖尿病密切相关。     

中国汉族人群PGC-1α基因rs3774923单核苷酸多态性与冠心病的关系

目的本研究探讨过氧化物酶增殖激活物受体辅助激活因子1α（peroxisome prolifemtor-activatedreeeptor γ coactivator-1,PGC-1α）基因rs3774923单核苷酸多态性与中国汉族人群冠状动脉粥样硬化性心脏病（冠心病）发病的关系。方法采用聚合酶链反应-限制性片段长度多态性方法对675例冠心病患者和636例对照组患者进行检验,分析PGC-1α基因rs3774923单核苷酸多态性的基因型和等位基因频率的分布情况。结果PGC-1α基因rs3774923单核苷酸多态性三种基因型（GG型,GA和AA型）在冠心病组的分布频率分别为60．0％,30．2％和9．8％,在对照组分别为58．2％,35．2％和6．4％,两组PGC-1α基因rs3774923单核苷酸多态性的基因型比较,差异无统计学意义（P〉0．05）。PGC-1α基因rs3774923单核苷酸等位基因（G等位基因,A等位基因）分布频率在冠心病组为75．1％和24．9％,在对照组为75．9％和24．1％,两组PGC-1α基因rs3774923单核苷酸多态性的等位基因频率比较,差异无统计学意义（P〉0．05）。Logistic回归分析校正性别、年龄、体质量指数、吸烟、原发性高血压、高脂血症、糖尿病等冠心病的易患因素后,PGC—1α基因rs3774923单核苷酸多态性与冠心病的发病不存在相关关系（P〉0．01）。结论PGC-1基因rs3774923单核苷酸多态性与冠心病的发病不存在相关关系。     

2型糖尿病相关基因多态性

2型糖尿病是一种多基因遗传性疾病，其遗传表型具有很大的异质性，研究2型糖尿病的基因多态性一直是人类基因研究的主要任务。近年来对过氧化物酶增殖物激活受体（PPAR）、PPAR-γ共刺激物-1（PGC-1）、胰岛素受体底物等的基因多态性进行了更为全面的研究。同时，2型糖尿病是许多具有不同功能的突变基因共同作用的结果，每个突变基因仅产生轻微的表现，基因不能从根本上决定2型糖尿病的发生，而是提供了环境因素发挥作用的基础。     

环氧化酶2基因-765G／C多态性与昆明地区汉族2型糖尿病患者糖尿病肾病发生、发展的关系

目的 探讨环氧化酶2基因启动子区-765G/C多态性与昆明地区汉族2型糖尿病患者糖尿病肾病发生、发展的相关性.方法 选取2008年1月至12月昆明医学院第一附属医院糖尿病科收治住院的2型糖尿病患者252例,根据24 h尿白蛋白排泄率或随机尿白蛋白/肌酐比值分至无糖尿病肾病组（n=100）、隐性糖尿病肾病组（n=78）、显性糖尿病肾病组（n=74）.运用聚合酶链反应-限制性片段长度多态性方法检测环氧化酶2基因启动子区-765G/C多态性.检测血糖、血脂和其他生化指标.运用χ^2检验比较各组基因型频率和等位基因频率,运用方差分析比较各组相关临床及生化指标,采用logistic回归分析评价影响糖尿病肾病发生、发展的危险因素.结果 两糖尿病肾病组-765GG基因型频率与无糖尿病肾病组存在明显差异（0.901 vs 0.810;χ^2=4.309,P＜0.05）.糖尿病肾病患者中,-765GG基因型携带者空腹血糖、餐后2 h血糖与非携带者存在明显差异[分别为（7.9±4.0）vs（5.9±1.7）mmol/L,（12±5）vs（9±4）mmol/L;t值分别为0.001、0.020,均P＜0.05＝.logistic回归分析提示,-765GG基因型是糖尿病肾病发生的独立危险因素之一[比值比（OR）=3.25,95%可信区间（CI）为1.336～7.901].结论 在昆明地区汉族2型糖尿病患者中,环氧化酶2基因启动子区-765GG基因型与糖尿病肾病的发生、发展有关.     

糖尿病患者基因组Mfn2启动子区PGC-1α及ERRα顺式作用元件的多态性分析

目的筛查2型糖尿病（T2DM）患者基因组线粒体融合蛋白2（Mfn2）启动子区过氧化物酶体增殖物受体1共激活因子1α（PCC-1α）及雌激素相关受体（ERRα）顺式作用元件的多态性。方法采用PCR-SSCP技术结合DNA测序技术。结果Mfn2启动子区PGC-1α及ERRα顺式作用元件处未发现多态性位点。结论T2DM患者PGC-1α调控的Mfn2表达下降，可能通过某些生理机制，而非遗传机制。     

中国汉族人群PGC-1α基因Thr394Thr和Gly482Ser变异在2型糖尿病家系中传递的不平衡分析

目的了解中国汉族人群PGC-1α基因Thr394Thr和Gly482Ser变异与2型糖尿病的相关关系。方法招募350名中国南方汉族2型糖尿病先证者及其一级亲属,抽提外周血DNA。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析和DNA直接测序技术鉴定PGC-1α基因型。基于2型糖尿病家系,采用单倍型相对危险度分析(HRR)和传递不平衡检验(TDT)方法分析Thr394Thr和Gly482Ser变异及其单倍型与2型糖尿病的关系。结果基于2型糖尿病家系的HRR分析显示,PGC-1α基因482Ser(A)等位基因更多向子代传递(χ~2=7.2170,P=0.0072,HRR=1.4496),而Thr394Thr(G/A)等位基因在传递与未传递两组间分布频率差异无统计学意义(χ~2=2.9557,P=0.0856,HRR=0.7638)。TDT分析提示,394Thr(A)-482Ser(A)单倍型在两组间分布差异有统计学意义(χ~2=33.160,P=0.002),且与2型糖尿病呈连锁不平衡关系(χ~2=4.6841,P=0.0292)。结论 394A-482A联合变异可能增加了中国人患糖尿病的风险。     

载脂蛋白J基因多态性与2型糖尿病相关性分析

用PCR-变性梯度凝胶电泳法研究载脂蛋白J基因外显子2和5的多态性，发现31例2型糖尿病（T2DM）病人的外显子5的突变杂合子频度高于正常对照（n=30）（100％us77％，P〈0．05），外显子2的突变杂合子频度也高于正常对照（61％us40％）。提示这种突变可能与T2DM有关。     

胰岛素受体底物-2基因多态性与2型糖尿病的相关性研究

目的 研究北京地区汉族人群中胰岛素受体底物-2（IRS-2）基因密码子1057g/a多态性与2型糖尿病及其中间表型的相关性。方法 选取北京地区的中国汉族患者110例，对照组80例。用聚合酶链反应-限制性内切酶片段长度多态性（PCR-RFLP）的方法检测IRS-2基因密码了1057g/a多态性。结果 （1）IRS-2基因密码子1057g/a多态性的a等位基因频率在糖尿病组和对照组中分别为26.4%和36.3%。（2）糖尿病组aa基因型频率明显低于对照组，分别为5.5%和18.7%(P=0.016),Logistic相关分析表明：aa基因型为2型糖尿病的保护性因素，OR值为0.28(95%CI=0.09-0.91,P=0.03)。（3）不同基因型组间血压、血脂，胰岛素抵抗指数及胰岛β细胞功能指数等均差异无显著性。结论 中国北方地区汉族人群中IRS-2基因密码子1057g/a多态性的aa基因型在2型糖尿病中明显减少。但2型糖尿病各种中间表型自欺欺人持征在不同基因型间均无明显差异。上述结果有待于进一步扩大样本量来加以确认。     

2型糖尿病患者内皮一氧化氮合酶基因(CA)n多态性的分布及与糖尿病肾病的关系

目的探讨内皮一氧化氮合酶基因（CA）n多态性在新加坡2型糖尿病患者中的分布及与糖尿病肾病的关系。方法258例2型糖尿病患者入选。从全血中提取DNA，然后进行多聚酶链反应、凝胶电泳及测序。结果在新加坡的中国人、马来西亚人和印度人中各有23、22、20种（CA）n多态性，其基因型分布差异有统计学意义（P〈0．01）。新加坡中国人（CA）n的分布与欧洲白人差异有统计学意义。该基因多态性与糖尿病肾病无显著相关性。结论（CA）n多态性在新加坡3个种族中的分布差异有统计学意义，而且与欧洲白人的分布差异也有统计学意义，但与糖尿病肾病无显著相关性。     

浆细胞膜糖蛋白1基因多态性与2型糖尿病合并冠状动脉粥样硬化性心脏病的关系

目的 探讨浆细胞膜糖蛋白1(PC-1)基因K121Q多态性与2型糖尿病及糖尿病合并冠状动脉粥样硬化性心脏病(冠心病)的关系.方法 应用聚合酶链反应-限制性酶切片段长度多态性分析(PCR-RFLP)技术检测糖尿病(DM组,n=80)及其合并冠心病患者(DC组,n=67)与健康对照组(n=83)的PC-1基因K121Q的多...     

不同类型糖尿病患者的血清干扰素γ诱导蛋白10的改变及其意义

目的探讨不同类型糖尿病患者的血清干扰素7诱导蛋白10（IP—10）水平及其意义。方法检测1型糖尿病（T1DM，n=78）、2型糖尿病（T2DM，n=49）和正常对照组（NC，n=33）的IP—10水平。T1DM组根据病情进展分为经典T1DM和成人隐匿性自身免疫糖尿病（LADA）组；又根据胰岛自身抗体IAA阳性与否分为自身免疫性T1DM和特发性T1DM组。T2DM组根据大动脉内中膜厚度IMT分为无动脉粥样硬化AS组和有AS组。Cl／SA检测各组IP-10水平。结果（1）IP-10水平在T1DM、T2DM与NC组之间无统计学差异。（2）胰岛自身抗体阳性的自身免疫性T1DM组IP-10水平高于NC组，差异有统计学意义，而T2DM与NC组无统计学差异；病程不同的T1DM IP-10水平无统计学差异。（3）伴或不伴动脉粥样硬化病变的T2DM亚组IP—10水平无统计学差异。结论自身免疫性1型糖尿病患者IP-10水平升高，可能与其介导Th1型细胞免疫反应有关。     

Common genetic basis between type 1 and type 2 diabetes mellitus indicated by interview-based assessment of family history

To investigate the intrafamilial clustering of type 1 and type 2 diabetes, an interview-based assessment of family history of diabetes was conducted. Outpatients with either type 1 (n = 23) or type 2 diabetes (n = 124), and non-diabetic subjects (n = 118) received an interview regarding the diabetic status of each of their family members. In patients with type 1 diabetes, 22% (5 out of 23) had a parental history of diabetes, and diabetes in these 5 parents was assessed as type 2 diabetes mellitus. The prevalence of parental diabetes in the type 1 diabetic probands (22%) was significantly higher (P < 0.05) than that in non-diabetic probands (7%, 8 out of 118). In probands with type 2 diabetes, the prevalence of parental diabetes was 39% (48 out of 124), which was significantly higher (P < 0.0005) than that in the non-diabetic probands (7%). In the type 2 diabetic probands, no significant difference was noted in the prevalence between paternal (19%, 23 out of 124) and maternal diabetes (23%, 28 out of 124), suggesting no preferential inheritance of maternal diabetes in this population. The present interview-based assessment of family history of diabetes suggested a common genetic basis between type 1 and type 2 diabetes.     

糖尿病患者血清基质金属蛋白酶9和血小板活化因子水平变化及意义

目的探讨糖尿病患者血清基质金属蛋白酶9（MMP-9）、血小板活化因子（PAF）水平变化及血糖（Glu）水平对其的影响。方法应用全自动生化分析仪分别检测30例糖尿病合并高Glu患者（高Glu组）、30例糖尿病Glu正常者（正常Glu组）、27例健康对照者（对照组）的Glu,ELISA法检测MMP-9,生物学方法检测血清PAF,并进行比较和相关分析。结果三组比较,高Glu组MMP-9、PAF水平最高,正常Glu组高于对照组（F=55.53,70.46,180.19;P均〈0.01）。相关分析显示高Glu组血清MMP-9与PAF、Glu水平呈正相关（r=0.539,0.881;P均〈0.01）。PAF与Glu水平呈正相关（r=0.429,P〈0.05）。糖尿病患者Glu正常组血清MMP-9与PAF水平呈正相关（r=0.820,P〈0.01）,MMP-9和PAF与Glu水平无相关。对照组血清MMP-9、PAF、Glu之间无相关性。结论高Glu可致MMP-9、PAF等炎症介质表达水平变化,监测及控制MMP-9、PAF水平对控制糖尿病并发症发生有重要意义。     

Profound reduction in T-helper (Th) 1 lymphocytes in peripheral blood from patients with concurrent type 1 diabetes and Graves' disease

Type 1 diabetes likely is mediated by T-helper (Th) 1 lymphocytes, while Graves' disease may involve Th2 predominance. We investigated the balance between Th1 and Th2 cells and between Th1- and Th2-associated chemokine receptor expression on peripheral lymphocytes in subjects including patients with coexisting type 1 diabetes and Graves' disease. Peripheral blood mononuclear cells of all subjects were examined by flow cytometry for intracellular cytokines (IFN-gamma for Th1; IL-4 for Th2) and expression of the chemokine receptors CXCR3 (Th1-associated) and CCR4 (Th2-associated). Plasma concentrations of interferon-inducible protein (IP)-10, a CXCR3 ligand, and thymus and activation-regulated chemokine (TARC), a CCR4 ligand, were measured by enzyme-linked immunosorbent assays. IFN-gamma producing-T lymphocytes were significantly fewer in patients with coexisting type 1 diabetes and Graves' disease (12.4 +/- 6.8%, n = 6) than in healthy control subjects (19.9 +/- 4.1%, n = 6; P < 0.01) or patients with type 2 diabetes (19.1 +/- 4.5%, n = 5; P < 0.05). We found no significant difference in IFN-gamma-producing T lymphocytes between healthy controls and patients with only type 1 diabetes (n = 8) or Graves' disease (n = 5). Plasma IP-10 concentrations were significantly higher in patients with coexisting type 1 diabetes and Graves' disease than in control subjects (106.3 +/- 30.48 vs. 66.7 +/- 25.3 pg/ml, P = 0.0343). Considering only patients with type 1 diabetes alone, duration of diabetes correlated positively with IFN-gamma-producing T lymphocytes (r = 0.773, P = 0.0242) and the ratio of CXCR3 to CCR4 receptor expression (r = 0.947, P = 0.0004). In conclusion, Th1-associated T lymphocytes were fewer in peripheral blood from patients having both type 1 diabetes and Graves' disease than in those with either disease alone. Numbers of peripheral Th1 lymphocytes increased with increasing time from onset of type 1 diabetes in patients with type 1 diabetes alone.     

The paraoxonase-2-310 polymorphism is associated with the presence of microvascular complications in diabetes mellitus

OBJECTIVE: To investigate the paraoxonase-2 (PON 2)-C/S 310 polymorphism and its relationship to the presence of diabetic complications and glycaemic control. DESIGN: Case-control study. SETTING: One study centre at University hospital. MATERIALS AND METHODS: The subjects were people with type 2 diabetes (n=252), type 1 diabetes (n=152) and healthy controls (n=282). The PON 2-C/S 310 polymorphism was measured by restriction fragment length polymorphism analysis. Lipids and lipoproteins were measured by standard clinical chemistry methods. Diabetes and diabetic complications were defined by World Health Organization criteria. RESULTS: There was an over-representation of the C/C 310 genotype in those with diabetes and microvascular complications (type 2 diabetes P=0.043, type 1 diabetes P=0.052, both populations combined P=0.014). The PON 2-C/S 310 polymorphism was also associated with glycaemic control. C 310/C 310 homozygotes had the highest HbA(1c) concentration (P=0.020 type 2 diabetes, P=0.065 type 1 diabetes, P=0.035 both populations combined). There was no association between the PON 2-310 polymorphism and lipid and lipoprotein concentrations. CONCLUSIONS: PON 2 could be directly involved in protecting critical enzymes or organelles against oxidative damage; PON2 may thus predispose to the development of microvascular complications.     

2型糖尿病合并冠心病患者血清血管细胞黏附分子-1水平及罗格列酮干预临床研究

目的:探讨血清血管细胞黏附分子-1(sVCAM-1)在2型糖尿病合并冠心病患者中的作用及罗格列酮干预的影响.方法:选取门诊及病房中单纯2型糖尿病患者(A组)40例、2型糖尿病合并冠心病患者(B组)40例及健康对照者(C组)40名,检测体重指数、血脂、血压、血糖、稳态模型胰岛素抵抗指数,酶联免疫吸附法测定sVCAM-1.2型糖尿病患者(A组、B组)均以罗格列酮(4 mg/d)干预治疗24周,于治疗前后检测上述各指标,进行不同治疗时段对照研究及指标间相关性研究.结果:A组、B组分别与C组比较体重指数、空腹血糖、餐后2 h血糖、稳态模型胰岛素抵抗指数、糖化血红蛋白A1c、甘油三酯、总胆同醇、低密度脂蛋白胆固醇均升高,高密度脂蛋白胆固醇降低(P＜0.05～0.01),差异有统计学意义;B组与c组比较收缩压、舒张压均升高(P＜0.05),差异有统计学意义;B组与A组比较收缩压、舒张压、稳态模型胰岛素抵抗指数、糖化血红蛋白A1c、甘油三酯均升高(P＜0.05),差异有统计学意义.sVCAM-1分别与体重指数、血压、空腹血糖、餐后2 h血糖、稳态模型胰岛素抵抗指数、糖化血红蛋白A1c、甘油三酯、总胆固醇、低密度脂蛋白胆固醇呈正相关,与高密度脂蛋白胆同醇呈负相关;A组sVCAM-1水平高于C组,B组sVCAM-1明显高于A组;罗格列酮干预后A组sVCAM-1均有不同程度下降.结论:应用罗格列酮治疗2型糖尿病合并冠心病后sVCAM-1有不同程度下降,提示罗格列酮对防治这类患者可能起一定的作用.     

Glycated albumin is a better indicator for glucose excursion than glycated hemoglobin in type 1 and type 2 diabetes

To determine the impact of blood glucose profile, involving fluctuation and excursion of blood glucose levels, on glycated proteins, we evaluated the association among the daily profile of blood glucose, and glycated albumin (GA) and HbA1c levels in patients with type 1 diabetes (n = 93) and type 2 diabetes (n = 75). GA levels were strongly correlated with HbA1c levels in type 1 (r = 0.85, P<0.0001) and type 2 diabetes (r = 0.61, P<0.0001), respectively. HbA1c levels were similar between patients with type 1 and type 2 diabetes, while GA levels were significantly higher in type 1 diabetes. Thus the ratio of GA levels to HbA1c levels was significantly higher in type 1 diabetes than that in type 2 diabetes (3.32 0.36 vs. 2.89 0.44, p<0.001). The degrees of GA levels and HbA1c levels correlated with maximum and mean blood glucose levels in patients with type 1 and type 2 diabetes. Stepwise multivariate analysis revealed that GA levels independently correlated with maximum blood glucose levels in type 1 diabetes (F = 43.34, P<0.001) and type 2 diabetes (F = 41.57, P<0.001). HbA1c levels also independently correlated with maximum blood glucose levels in type 1 diabetes (F = 34.78, P<0.001), as well as being correlated with mean blood glucose levels in type 2 diabetes (F = 11.28, P<0.001). In summary, GA could be a better marker for glycemic control than glycated hemoglobin in diabetic patients, especially for evaluating glycemic excursion, which is considered to be a major cause of diabetic angiopathy.     

2型糖尿病并难治性高血压抗β1肾上腺素能和M2胆碱能受体自身抗体与蛋白尿的关系

目的 探讨糖尿病并难治性高血压患者β1和M2受体自身抗体与蛋白尿的关系.方法 以合成的β1和M2受体多肽片段为抗原,应用酶联免疫吸附测定(ELISA)技术,检测136例糖尿病并难治性高血雎患者[A组,A组分为蛋白尿组(尿蛋白排泄率≥20μg/min,91例)和正常蛋白尿组(UAER<20 μg/min,45例),蛋白尿组根据UAER水平分为蛋白尿1组(UAER≥200 μg/min)和蛋白尿2组(UAER 20～199μg/min)];111例糖尿病并高血压患者(B组);60例高血压无肾损患者(C组)及40例正常人(D组).血清中抗G-蛋白偶联型β1和M2受体自身抗体,尿蛋白排泄率用ELISA技术检测.结果 (1)A组抗β1和M2受体抗体阳性率为44.9%(61/136)和37.5%(51/136),明显高于B组的27.9%(31/111)和24.3(27/111)明显高于C组的11.7%(7/60)和15.0%(9/60)及D组8.3%(5/40)和7.5%(3/40),组间比较差异有统计学意义(P<0.01).(2)A组中蛋白尿组抗β1和M2受体抗体阳性率分别为60.4%(55/91)和50.5%(46/91)明显高于A组中正常蛋白尿组13.3%(6/45)和11.1%(5/45),组间比较具有统计学意义(P<0.01).(3)蛋白尿1组抗β1和M2受体自身抗体阳性率为87.1%(27/31)和67.7%(21/31),明显高于蛋白尿2组的46.7%(28/60)和41.7%(25/60)及正常蛋白尿组的13.3%(6/45)和11.1%(5/45),组间比较差异有统计学意义(P<0.01).结论 肾损害越严重,尿蛋白水平越高,抗β1和M2受体自身抗体阳性率也越高.提示自身免疫机制参与可能是引起糖尿病并难治性高血压肾损害的重要因素之一.     

高尿酸血症与2型糖尿病并发症相关因素的研究

目的：研究2型糖尿病（T2DM）患者血尿酸相关因素,探讨高尿酸血症与2型糖尿病并发症的关系。方法：收集365例T2DM患者的临床资料,按血尿酸水平分为高尿酸组（102例）及正常尿酸组（263例）,比较两组一般临床资料及并发症发病情况,采用偏相关分析法分析高尿酸血症的相关危险因素。结果：尿酸与三酰甘油、血压等呈正相关（P〈0．05）;T2DM并高尿酸组的高血压、冠心病、脂代谢紊乱的发生率明显升高。结论：T2DM患者尿酸水平与多因素相关,提示高尿酸血症是T2DM并发症发病的危险因素之一。     

2型糖尿病患者血清可溶性细胞间粘附分子1水平变化及与血管内皮功能的关系

目的研究2型糖尿病患者血清可溶性细胞间粘附分子1水平的变化,并以血浆假性血友病因子水平作为内皮功能损伤的指标,观察细胞间粘附分子1与血管内皮细胞功能损伤之间的关系。方法62例2型糖尿病患者按照有无血管并发症分为无血管病变组(n=19)、微血管病变组(n=20)和大血管病变组(n=23),选择20例健康者作为对照组。应用酶联免疫吸附法检测各组患者血清可溶性细胞间粘附分子1水平和血浆假性血友病因子水平,并测定糖脂代谢指标和尿微量白蛋白水平。结果2型糖尿病患者血清可溶性细胞间粘附分子1水平明显高于健康对照组(P<0.01),在无血管病变组、微血管病变组和大血管病变组的水平逐步升高(P<0.01);血浆假性血友病因子水平在大血管病变组高于微血管病变组,微血管病变组高于无血管病变组(P<0.01),无血管病变组与对照组间无显著性差异。可溶性细胞间粘附分子1与血浆假性血友病因子、甘油三酯、收缩压、舒张压呈正相关(r分别为0.43、0.45、0.52和0.62,P<0.01)。结论细胞间粘附分子1可能参与了2型糖尿病血管病变的发生和发展,可作为早期2型糖尿病患者慢性血管并发症尤其是大血管病变发生的预测及监测指标。