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dc.contributor.author张渭涛
dc.date.accessioned2019-10-26T02:19:55Z
dc.date.available2019-10-26T02:19:55Z
dc.date.created2017-09-28 23:45
dc.date.issued2016
dc.identifieroai:ir.xjtu.edu.cn:itemNo:435710
dc.identifierhttp://ir.xjtu.edu.cn/item/435710
dc.identifier.urihttp://hdl.handle.net/20.500.12424/1530898
dc.description.abstract2型糖尿病(Type 2 diabetes mellitus,T2DM)约占糖尿病患者总数的90%以上,大部分在35岁以后发生,其发病一般较为隐匿。T2DM患者早期并不是胰岛素(insulin,INS)合成能力丧失,而是INS的作用下降,是一种相对的INS缺乏,称为胰岛素抵抗(insulin resistance,IR),随着疾病进展可出现分泌不足[1]。临床上常使用胰岛素增敏剂如吡格列酮和二甲双胍治疗T2DM[2,3]。有研究表明吡格列酮可以通过影响2型糖尿病患者肠源性内毒素水平缓解机体的慢性炎症反应,并进一步改善患者的胰岛素抵抗情况[4]。本研究分别采用吡格列酮和二甲双胍治疗105例2型糖尿病患者,旨在观察这两种药物对其肠源性内毒素等指标水平的影响。 目的: 探究吡格列酮和二甲双胍对初诊T2DM患者肠源性内毒素水平的影响。 研究材料: 选取我院2014年2月至2015年2月收治的初诊T2DM患者,采用双盲双模拟随机对照研究方法,分为吡格列酮治疗组和二甲双胍治疗组,并选择同期本院性别、年龄匹配的健康体检者作为对照组。该方案已获医学研究伦理委员会审批。 病例入选标准必须同时满足以下条件:①患者经1月以上的饮食和运动治疗后空腹血糖(FPG)仍在7.8-13.9mmol/L之间或者餐后2小时血糖(2hPG)大于11.1mmol/L;②未用胰岛素治疗;③知情同意并签署知情同意书。 有以下条件之一的病例需去除:①患者在4周内出现全身或局部感染,或是血清中高敏C反应蛋白(hs-CRP)超过10mg/L[5];②患者有胃肠道、心、肝、肾等脏器病史,或者患有肿瘤、自身免疫性疾病;③诊断时伴有急性并发症;④妊娠期妇女;⑤不能完成知情同意者。 根据纳入、排除标准以及发生不良反应退出等因素,本研究共纳入初诊2型糖尿病患者105例,随机分为吡格列酮治疗组52例(包括男性25例,女性27例)和二甲双胍治疗组53例(包括男性27例,女性26例);纳入对照组42例(包括男性22例,女性20例)。 研究方法: 本研究的所有患者均首先进行一个月的饮食控制和运动治疗。吡格列酮治疗组患者于早餐结束后口服30mg吡格列酮片,并于早餐和晚餐后分别口服1片安慰剂;二甲双胍治疗组早餐后口服二甲双胍片1片(500mg)及安慰剂2片,晚餐后口服二甲双胍片1片(500mg)。两组疗程均为12周。 收集对照组和两治疗组研究对象的临床资料和各项临床指标,包括年龄、身高、体重、治疗前后的空腹血糖水平(FPG)、餐后2小时血糖水平(2hPG)、甘油三酯(TG)、总胆固醇(TC)、空腹胰岛素水平(FINS)、餐后2小时胰岛素水平(2hINS)、肠源性内毒素、血清高敏C反应蛋白(hs-CRP)等。 分别采取葡萄糖氧化酶法和放免法测定患者血浆中血糖和胰岛素指标。使用体重指数(BMI)评价研究对象的一般情况,计算公式BMI=体重(kg)/[身高(m)]2;患者胰岛素抵抗采用HOMA-IR进行评价,该指数的计算公式为:HOMA-IR=空腹胰岛素×空腹血糖/22.5。 采用统计学软件SPSS 19.0对数据进行分析,计量资料用(x(—)±s)表示,各组均数比较使用方差分析,两两比较采用SNK-q检验,计数资料采用χ2检验,P<0.05说明差异有统计学意义。 结果: 1. 吡格列酮治疗组、二甲双胍治疗组患者的年龄、治疗前的BMI与对照组相比均无显著性差异,且两个治疗组治疗前FPG、2hPG、TG、TC、FINS、2hINS、肠源性内毒素、hs-CRP等指标相比无显著差异(P>0.05),但其FPG、2hPG、2hINS、HOMA-IR、TG、TC、肠源性内毒素和血清hs-CRP水平均显著高于对照组(P<0.05或P<0.01)。吡格列酮治疗组患者治疗前后BMI变化不明显(P>0.05),但二甲双胍治疗组患者治疗后BMI较治疗前明显降低(P<0.05)。 2. 两治疗组患者经过12周治疗后,其FPG、2hPG、FlNS、2hINS和HOMA-IR等指标均有明显降低(P<0.05或P<0.01)。经过12周的吡格列酮治疗,TG由(3.8±1.2)mmol/L下降至(1.6±0.3)mmol/L,差异显著(P<0.05),但TC下降不明显;而二甲双胍治疗前后TG和TC均无明显变化(P>0.05),这说明吡格列酮对患者脂代谢的改善效果优于二甲双胍。对肠源性内毒素和hs-CRP水平进行分析发现,吡格列酮治疗后二者均下降较为明显,且具有统计学意义(P<0.01);但二甲双胍治疗后,只有hs-CRP降低有统计学意义(P<0.05),肠源性内毒素下降不显著。但是两种药物治疗后,患者肠源性内毒素水平仍高于对照组(P<0.01)。 结论: 两治疗组治疗前FPG、2hPG、FINS、2hINS、TG、TC、肠源性内毒素水平、hs-CRP等指标无显著差异,但与对照组相比明显升高,这说明2型糖尿病患者与正常人群相比,除血糖、血脂存在代谢紊乱以外,肠源性内毒素、hs-CRP等炎性因子的水平明显升高,提示了2型糖尿病患者体内存在慢性低度炎症,而这可能是导致胰岛素抵抗(IR)和各种代谢紊乱的主要原因。研究表明口服吡格列酮虽可使患者内毒素水平显著下降,口服二甲双胍则对2型糖尿病患者内毒素水平无明显影响,但两组治疗后内毒素水平仍明显高于对照组。从治疗组治疗前后血脂TG、TC的变化来看,吡格列酮对TG的影响明显,该组患者TG的水平下降明显,但TC的下降不明显;二甲双胍组治疗前后TG、TC的变化均不明显,说明与二甲双胍相比,吡格列酮对患者脂代谢的改善效果更好。 关 键 词:吡格列酮;二甲双胍;肠源性内毒素;2型糖尿病 论文类型:应用研究
dc.description.abstractAlmost 90% of all diabetes patients are type 2 diabetes mellitus (T2DM). Generally T2DM occured after 35 years old and its progress was dormant. In the early stage, T2DM patients don’t lose the ability of synthesizing insulin, but their function of insulin could decline.It is the relative insulin deficiency, which is called insulin resistance (IR).There will be insulin hyposecretion with the progress of the diaease. Pioglitazone as insulin sensitizers and metformin are usually used to treat T2DM in clinical therapy.Previous research has shown that pioglitazone can relieve the chronic inflammatory reaction by affecting intestinal endotoxin level of T2DM patients, and further improve insulin resistance. In our study, 105 T2DM patients were treated by pioglitazone and metformin respectively, in order to observe the effects of the two drugs on the markers such as intestinal endotoxin level. Objective: To explore the effects of pioglitazone and metformin on intestinal endotoxin level of newly diagnosed T2DM patients. Material: The newly diagnosed T2DM patients are selected in our hospital from February 2014 to February 2015. They are divided into pioglitazone treatment group and metformin treatment group by randomized, double-blind, double simulation, controlled method and gender and age of selected are matched with healthy people who were taking physical examination during the same period as control group. This study plan has been approved by medical ethics committee. The included patients must meet the following conditions at the same time: 1. Fasting plasma glucose (FPG) could maintain at 7.8-13.9mmol/L after over one-month controlled diet and exercise therapy or 2-hr plasma glucose (2hPG) was above 11.1mmol/L; 2. They haven’t been treated by insulin; 3. All the patients and volunteers signed the informed consent. Exclusion criteria meet one of the following conditions: 1. Systemic or local infection of patients occurs in 4 weeks or high sensitivity C reactive protein in serum (hs-CRP) goes beyond 10mg/L;2. Patients with medical history such as gastrointestinal, heart, liver, kidney and other organ, or suffering from cancer, autoimmune diseases; 3. Patients with acute complications of diabetes mellitus; 4.Pregnant women; 5. Patients who could’t complete informed consent. According to the inclusion and exclusion criteria and the factors of exit due to adverse reaction, this study in total included 105 newly diagnosed T2DM patients which were randomly divided into pioglitazone treatment group (52 in total, 25 male, 27 female) and metformin treatment group (53 in total, 27 male, 26 female); Control group included 42 in total (22 male, 20 female). Methods All patients in this study should be treated with controlled diet and exercise therapy at least one month. Patients in pioglitazone treatment group took 30mg pioglitazone tablets and 1 tablet placebo after breakfast, and 1 tablet placebo after dinner; Patients in metformin treatment group took 1 tablet metformin (500mg) and 2 tablets placebo after breakfast, and 1 tablet metformin (500mg) after dinner. Both of the two groups were treated for 12 weeks. We collected the clinical data and indicators of the two treatment groups and control group, including age, height, weight, FPG before and after treatment, 2hPG, serum triglyceride (TG), total cholesterol (TC), fasting insulin (FINS), 2h-insulin (2hINS), intestinal endotoxin, hs-CRP and so on. Blood glucose and insulin levels were measured by glucose oxidase method and radio immunoassay method respectively. The height and weight of study objective were evaluated by BMI. BMI=weight (kg)/[height(m)]2;Insulin resistance was evaluated by HOMA-IR, equation: HOMA-IR=fasting insulin x FPG / 22.5. Statistical analysis was done by SPSS 19.0 software package. Measurement data was showed with(x(—)±s). The comparison of multiple groups mean was analyzed by variance. Further paired comparison was done with SNK-q test. Count data was processed by χ2 test. The difference was statistically significant when P<0.05. Results: Compared with control group, there was no significant difference with age and BMI before treatment between pioglitazone treatment group and metformin treatment group.There was no significant difference between the indicators (FPG, 2hPG, TG, TC, FINS, 2hINS,intestinal endotoxin, hs-CRP, etc.) of the two treatment groups before treatment (P > 0.05), but levels of the indicators(FPG, 2hPG, 2hINS, HOMA-IR, TG, TC, intestinal endotoxin, hs-CRP) were significantly higher than control group (P<0.05 or P<0.01). In pioglitazone treatment group the changes of BMI were insignificant after treatment (P>0.05), but BMI of metformin treatment group declined significantly (P<0.05). After the treatment for 12 weeks, indicators (FPG, 2hPG, FlNS, 2hINS, HOMA-IR, etc.) of the two treatment groups declined significantly or extreme significantly (P<0.05 or P<0.01). For pioglitazone treatment group, TG declined from (3.8±1.2)mmol/L to (1.6±0.3)mmol/L (P<0.05), but the decline of TC was not significant; There were no significant changes with both TG and TC for metformin treatment group (P>0.05). It was showed that pioglitazone in improving glycometabolism of diabetes patients is better than metformin. Meanwhile the levels of intestinal endotoxin and hs-CRP significantly declined for pioglitazone treatment group with statistical difference (P<0.01); but for metformin treatment group only decline of hs-CRP was statistically significant (P<0.05). Decline of intestinal endotoxin was insignificant. However intestinal endotoxin levels of the two treatment groups were still higher than control group after treatment (P<0.01). Conclusion: There was no significant difference between the indicators (FPG, 2hPG, TG, TC, FINS, 2hINS, intestinal endotoxin, hs-CRP, etc.) of the two treatment groups before treatment, but levels of the indicators(FPG, 2hPG, 2hINS, HOMA-IR, TG, TC, intestinal endotoxin, hs-CRP) were significantly higher than control group. The results of this study showed that compared to healthy people,the inflammatory factors such as intestinal endotoxin and hs-CRP level in T2DM patients significantly increased besides glycometabolism and lipid metabolism disorders. This study also found that there was chronic low-grade inflammation in the body of T2DM patients, and this may be the main cause of insulin resistance(IR) and a variety of metabolism disorders. This study showed that the level of intestinal endotoxin in T2DM patients of taking pioglitazone per os could decline significantly, but it was no significant changes in T2DM patients of taking metformin per os, however it was still higher than that in healthy people after treatment. From the changes of TG and TC before and after treatment in two treatment groups, the influence of pioglitazone on TG was significant, in pioglitazone treatment group TG declined significantly, but the decline of TC was not significant; There were no significant changes with both TG and TC for metformin treatment group. It was showed that pioglitazone in improving lipid metabolism of diabetes patients is better than metformin. KEY WORDS:Pioglitazone;Metformin;Intestinal endotoxin;Type 2 diabetes mellitus TYPE OF THSIS:Applied Rsearch
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dc.languagecn
dc.language.isochi
dc.source学位论文库
dc.subjectThesis
dc.title吡格列酮和二甲双胍对初诊T2DM患者 肠源性内毒素水平的影响
dc.typeTEXT
ge.collectioncodeOAIDATA
ge.dataimportlabelOAI metadata object
ge.identifier.legacyglobethics:11597153
ge.identifier.permalinkhttps://www.globethics.net/gel/11597153
ge.lastmodificationdate2017-09-28 23:45
ge.lastmodificationuseradmin@pointsoftware.ch (import)
ge.submissions0
ge.oai.exportid148650
ge.oai.repositoryid98506
ge.oai.streamid2
ge.setnameGlobeEthicsLib
ge.setspecglobeethicslib
ge.linkhttp://ir.xjtu.edu.cn/item/435710


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