那格列奈和瑞格列奈治疗2型糖尿病有效性和安全性的临床研究

目的:评价那格列奈治疗2型糖尿病的疗效和安全性。方法:采用多中心、随机、双盲、双模拟平行对照研究,观察那格列奈(A组,119例,120 mg 3/d)和瑞格列奈(B组,120例1.0 mg 3/d)治疗12周前后糖化血红蛋白(HbA1c)、血糖、胰岛素水平、体重及安全性指标的变化。结果:那格列奈和瑞格列奈均能有效降低HbA1c(P均<0.01)、空腹血糖(FPG,P分别<0.01和0.05)、餐后1 h、2 h血糖(PPG1、PPG2,P均<0.01),提升餐后1 h、2 h胰岛素(INS1,P均<0.01;INS2,P分别<0.01和0.05)水平。其中对HbA1c和FPG的疗效,那格列奈优于瑞格列奈(P分别<0.05和0.01),但前者低血糖反应也多于后者。两组的体重较治疗前均略有增加;两药安全性及顺应性较好。结论:那格列奈和瑞格列奈都是治疗2型糖尿病有效和安全的药物,那格列奈120 mg 3/d降低HbA1c和空腹血糖的效果强于瑞格列奈1.0 mg 3/d。     

中国门诊2型糖尿病患者口服药降糖达标状况调查及格列齐特缓释片优化治疗效果分析

Objective To evaluate the current state of glycemie control in Chinese patients with type 2 diabetes mellitus who have received oral antidiabetic agents in the out-patient clinic,and the efficacy and safety of optimized regiments of gliclazide modified-release tablets (Diamicron MR, SERVIER, Tianjin) in patients with failed glycemic control (HbA1c 6.5%). Methods The patients with type 2 diabetes were enrolled from 54 hospitals in more than 20 cities and received long-term (more than 3 months) oral antidiabetic agents. HbA1c was measured and the success rate of HbA1c reduction was evaluated. The patients who failed to achieve glycemic control (HbA1c 6. 5%) and received daily multiple-dosing insulin secretagogues were provided with the optimized treatment regimen, consisting of replacing daily multiple-dosing insulin secretagogues with single-dosing gliclazide sustained-release tablets. Clinical efficacy and safety were evaluated after three months treatment. Results The survey of glycemic control revealed that the mean HbA1c of 5 586 patients with diabetes mellitus was (7.97±2.89)% ,and the success rate (HbA1c≤6.5%) was 14. 1%. Further more, HbA1c decreased from (8.23±4.00)% before optimization to (6.86±2.24)% after optimization with the average decrement of 1.37% (P<0. 001) and the success rate was raised to 34. 1%. The gliclazide modified-release tablets were well tolerated by most patients, only 2.6% of whom were reported to experience unconfirmed hypoglycemia. Conclusion The success rate of glycemic control was low in Chinese out-patients with type 2 diabetes mellitus receiving oral antidiabetic agents in the clinic. The optimized regimen of gliclazide modified-release tablets taken once daily can down-regulate glycemic levels and increase the success rate of HbA1c reduction,and thus plays efficiently and safely a key role in the optimized management of type 2 diabetes mellitus.     

二甲双胍对脂肪肝作用机制的实验研究

目的观察胰岛素抵抗大鼠肝脏脂肪聚积和胆固醇调节元件结合蛋白-1(SREBP-1)表达并研究二甲双胍对脂肪肝的作用。方法分3组:设LETO大鼠为对照组,OLETF大鼠随机分为模型组和治疗组(二甲双胍每天100mg·kg-1)。于治疗后9,22周,测定肝组织甘油三酯含量;用WesterBlot方法测定肝脏SREBP-1蛋白表达水平;用定量PCR方法测定SREBP-1及参与其裂解的蛋白。结果与对照组比较,模型组大鼠肝组织甘油三酯含量增高,肝脏SREBP-1mRNA和蛋白表达水平升高,其靶基因脂肪酸合成酶(FAS)的mRNA表达增加。治疗后,与模型组比较,治疗组甘油三酯含量下降;治疗9周后,S1P和S2P mRNA水平下降;治疗22周后,肝脏SREB-1的mRNA表达水平下调。结论OLETF大鼠肝脏SREBP-1高表达,促进脂肪肝形成;二甲双胍可通过下调SREBP-1的表达,改善肝脏脂肪沉积。     

中国门诊2型糖尿病患者口服药降糖达标状况调查及格列齐特缓释片优化治疗效果分析

Objective To evaluate the current state of glycemie control in Chinese patients with type 2 diabetes mellitus who have received oral antidiabetic agents in the out-patient clinic,and the efficacy and safety of optimized regiments of gliclazide modified-release tablets (Diamicron MR, SERVIER, Tianjin) in patients with failed glycemic control (HbA1c 6.5%). Methods The patients with type 2 diabetes were enrolled from 54 hospitals in more than 20 cities and received long-term (more than 3 months) oral antidiabetic agents. HbA1c was measured and the success rate of HbA1c reduction was evaluated. The patients who failed to achieve glycemic control (HbA1c 6. 5%) and received daily multiple-dosing insulin secretagogues were provided with the optimized treatment regimen, consisting of replacing daily multiple-dosing insulin secretagogues with single-dosing gliclazide sustained-release tablets. Clinical efficacy and safety were evaluated after three months treatment. Results The survey of glycemic control revealed that the mean HbA1c of 5 586 patients with diabetes mellitus was (7.97±2.89)% ,and the success rate (HbA1c≤6.5%) was 14. 1%. Further more, HbA1c decreased from (8.23±4.00)% before optimization to (6.86±2.24)% after optimization with the average decrement of 1.37% (P<0. 001) and the success rate was raised to 34. 1%. The gliclazide modified-release tablets were well tolerated by most patients, only 2.6% of whom were reported to experience unconfirmed hypoglycemia. Conclusion The success rate of glycemic control was low in Chinese out-patients with type 2 diabetes mellitus receiving oral antidiabetic agents in the clinic. The optimized regimen of gliclazide modified-release tablets taken once daily can down-regulate glycemic levels and increase the success rate of HbA1c reduction,and thus plays efficiently and safely a key role in the optimized management of type 2 diabetes mellitus.     

对一个Liddle综合征家系临床和上皮细胞钠通道基因突变的研究

目的 通过对1个Liddle综合征家系的临床表现及其上皮细胞钠通道β亚单位（hβENaC）基因的研究,揭示本家系发病的遗传机制,为诊断（尤其产前诊断）和治疗提供有力的保证。方法 （1）对家系成员进行常规体检及血钾、血浆肾素活性、醛固酮水平测定;（2）用单链变构多态性PCR－DNA测序等分子生物学方法对hβENaC基因进行分析。结果 在这个Liddle家系中发现了hβENaC基因（SCNN1B）的1个移码突变（1bp,INS,600G),8个成员携带此突变基因,他们均有严重的高血压、低醛固酮及低肾素活性。50个无关正常人中无突变基因。结论 在这个Liddle综合征家系中发现的hβENaC基因的移码突变很可能为此家系的致病基因。     

长期强化降血糖及降血脂治疗逆转初发的2型糖尿病患者颈动脉内中膜厚度

目的:探讨初发的2型糖尿病(type 2 diabetes mellitus,T2DM)患者颈动脉内中膜厚度(carotid intima medial thickness ,IMT)的影响因素,并研究血糖及血脂的强化治疗能否逆转T2DM患者的IMT.方法:T2DM患者116例,常规测定收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、体重指数(body mass index,BMI)、腰/ 臀比(waist-to-hip ratio,WHR)、空腹血糖(fasting blood glucose,FBG)、总胆固醇(total cholesterol,TC)、甘油三酯 (triglycerides,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、糖化血红蛋白(hemoglobin A1c,HbA1c),测定餐后2 h血糖(2 h postpradial glucose,2hPG),高分辨血管外超声方法检测IMT,分析IMT与上述指标的相关关系.对其中的89例T2DM患者追踪观察,随机分为强化血糖及血脂治疗组和常规治疗组,1年后再次测定IMT水平.结果: (1)T2DM 患者IMT水平与年龄、SBP、TC、LDL-C呈显著正相关,多元逐步回归分析表明年龄、TC是影响IMT的独立危险因素. (2)T2DM患者血糖及血脂强化治疗后IMT变化值与常规组比较差异有统计学意义,IMT在强化血糖及血脂组呈现下降趋势,而常规治疗组呈现上升的趋势.(3)IMT前后变化值与二甲双胍、磺脲类药物、阿司匹林的使用与否无明显相关,和他汀类药物的使用与否有显著相关,IMT在他汀类药物使用组呈现下降趋势,而他汀类药物未使用组呈现上升趋势.结论:T2DM 患者IMT主要受年龄、TC的影响,强化血糖和血脂可以逆转IMT,他汀类药物使用可有助于逆转IMT.     

非诺贝特及二甲双胍对OLETF大鼠肾损伤和脂质沉积的影响

目的:探讨自发性2型糖尿病的动物模型OLETF大鼠在糖尿病前期时肾脂质代谢异常与早期肾病变的关系,肾脂质代谢异常的分子机制,以及非诺贝特或二甲双胍治疗对肾脂质代谢及肾病变的影响.方法:8周龄雄性OLETF大鼠,随机分为非诺贝特治疗组(OLETF/F)、二甲双胍治疗组(OLETF/M)和未治疗组,LETO大鼠为正常对照组.于17周龄及30周龄时分别杀检,测定24h尿白蛋白定量,肾皮质中甘油三酯的含量,肾皮质固醇调节元件结合蛋白-1(sterol regulatory element-binding protein 1,SREBP-1)的蛋白及mRNA表达,脂肪酸合成酶(fatty acid synthase,FAS)和乙酰辅酶A羧化酶(acetyl CoA carboxylase,ACC)的mRNA表达水平.结果:OLETF大鼠具有肥胖、高血糖、高胰岛素血症、高血脂的特点.30周龄时OLETF大鼠未治疗组与正常对照组比较,24h尿微量白蛋白显著升高,出现肾早期损伤.OLETF大鼠24 h尿白蛋白定量与肾甘油三酯含量呈正相关(r=0.870,P=0.011),随着肾甘油三酯含量加重,24 h尿白蛋白定量增多.OLETF大鼠未治疗组与正常对照组比较,调节脂肪合成的分子SREBP-1蛋白水平、FASmRNA、ACCmRNA分别升高43.2%(P＜0.01),126.0%(P＜0.01),72.3%(P＜0.01).OLETF/F组的SREBP-1蛋白水平、FASmRNA、ACCmRNA分别低于OLETF未治疗组15.7%(P=0.061),36.8%(P＜0.05),40.3%(P＜0.05).OLETF/M组的SREBP-1蛋白水平、FASmRNA、ACCmRNA分别低于OLETF未治疗组19.3%(P＜0.01),57.3%(P＜0.01),22.5%(P＜0.05).SREBP-1的mRNA水平在各组之间比较差异无统计学意义.结论:OLETF大鼠在糖尿病前期已经出现肾病变,可能与肾脂肪沉积有关.肾组织中SREBP-1水平升高,通过调节FAS,ACC等脂肪合成相关的酶,增加肾脂肪沉积,这可能是糖尿病肾病的发生机制之一.早期给予非诺贝特或二甲双胍治疗,可以减轻OLETF大鼠肾早期病变,可能通过SREBP-1及其下游脂肪合成相关酶的变化,直接改善了肾组织中的脂肪沉积.     

中华医学会糖尿病学分会第十四次全国学术会议纪要

一、会议概况 中华医学会糖尿病学分会（CDS）第十四次全国学术会议于2010年11月18日至20日在历史古城苏州召开。本次年会正式注册的参会代表4532人，实际到会人数近5000人，为历史之最。会议由CDS主任委员纪立农担任大会主席，副主任委员贾伟平及委员郭晓蕙担任大会副主席及执行主席。会议共开展3场主题报告、22场专题研讨，近70名中外学者作了丰富和高水平的学术报告。     

2009-2012年我国2型糖尿病患者药物治疗与血糖控制状况调查

目的 了解近4年我国T2DM患者血糖控制状况及治疗情况变化。 方法 由中华医学会糖尿病学分会“糖化血红蛋白监测网”项目组于2009-2012年连续4年在全国范围内选择各省/市具有代表性的重点医院门诊就诊的T2DM患者参加本横断面研究，按照《数据采集标准操作流程（SOP）》询问患者。收集了解患者人口学信息、治疗方案、血糖控制情况，并填写至《监测网登记表》。以HbAlc〈7.0%为达标。所有数据采用描述性统计分析。 结果 2009-2012年参加调研的T2DM患者分别为143123、172199、238656和223114例;至少有1种伴随疾病比例分别为63.8%、54.7%、52.1%和48.6%;平均HbAlc水平分别为7.97%、7.89%、7.85和7.74%;HbAlc达标率分别为35.28%、32.33%、31.77%和30.15。最常见的合并伴随疾病为高血压和血脂异常。 结论 我国T2DM患者HbAlc总体达标率低;约50%的T2DM患者合并至少1种伴随疾病。因此，多重危险因素的综合干预策略尤为重要。