【作者】 吕佳璘；

【导师】 王旭；

【作者基本信息】 南京中医药大学 ， 中西医结合临床， 2013， 博士

【摘要】 目的：探讨中医学对2型糖尿病合并代谢综合征的认识,通过临床研究,采用糖脂清治疗糖尿病合并代谢综合征,客观评价糖脂清对2型糖尿病合并代谢综合征患者的治疗效果,尤其是对中医证候积分、体质量指数、腰臀围、血压、血糖、血脂、胰岛素等方面所产生的影响,并评价其临床疗效及安全性,为临床应用提供客观依据。通过实验研究,探讨糖脂清方对2型糖尿病合并代谢综合征模型大鼠血脂水平、胰岛素抵抗指数、炎症细胞因子及氧化应激指标的作用,明确糖脂清方对糖脂代谢及胰岛素抵抗的影响。方法：临床研究采用随机、对照的研究方法,将符合2型糖尿病合并代谢综合征的患者,按1：1对照原则,随机分为对照组和治疗组。在基础治疗和西药常规治疗的基础上,对照组给予二甲双胍片0.5g,每日3次；辛伐他汀,10mg,每日1次；厄贝沙坦,150mg,每日1次；盐酸吡格列酮片,15mg,每日1次,治疗组给予中药水煎剂每日1剂,分早晚两次服用。以4周为1个疗程,观察3个疗程。治疗前后两组分别评价其临床症状、体征的变化,治疗前后观测中医证候积分、体质量指数、腰臀围、血压、血糖、血脂、空腹胰岛素、胰岛素敏感指数等指标。全部数据以SPSS19.0统计软件进行统计学分析。实验研究在加喂含丙基硫氧嘧啶的高脂高糖饮食基础上,小剂量链脲佐菌素造成2型糖尿病合并代谢综合征大鼠模型。将造模成功后的大鼠分为模型组、糖脂清组、吡格列酮组,另设正常对照组,给药8周后观察各组大鼠下列变化：血糖、血脂水平,胰岛素抵抗指数、炎症细胞因子及氧化应激指标。结果：临床研究：2型糖尿病合并代谢综合征患者60例随机分为2组,治疗组30例,对照组30例,治疗前两组的性别、年龄、病程等基线数据经统计学处理无显著性差异,有可比性。1、对症状体征的改善作用：治疗组患者治疗后症状有明显改善,治疗组中医症状改善情况优于对照组(P<0.01)。2、降糖效果：治疗组与对照组患者空腹血糖、餐后血糖均明显降低,与治疗前比较均有显著性差异(P<0.01)；治疗组治疗后空腹血糖改善较对照组有显着差异(P<0.05),治疗组餐后血糖改善较对照组有差异(P<0.05),治疗组糖化血红蛋白的改善较对照组有差异(P<0.05)。3、改善血脂水平：治疗组和对照组患者治疗后TG、TC、LDL-C水平下降,HDL-C水平升高,与治疗前比较均有显著性差异(P<0.01)。组间比较治疗组TG、TC、HDL-C水平改善均较对照组具有显著性差异(P<0.01),LDL-C水平改善均较对照组具有差异(P<0.05)。4、肥胖相关指标方面：治疗后两组患者BMI均降低,但差异无统计学意义(P>0.05)；治疗组BMI的变化较对照组无显著性差异(P>0.05)。治疗后两组患者体重、BMI有所降低,与治疗前比较均有显著性差异(P<0.01)；治疗组体重改善较对照组有显著性差异(P<0.01),治疗组BMI改善较对照组有差异(P<0.05);两组治疗后腰围、臀围、腰臀比与治疗前比较：治疗组的腰围和腰臀比均有显著性差异(P<0.01),治疗组在臀围及对照组在腰围、臀围、腰臀比方面无明显差异(P>0.05),治疗后治疗组与对照组腰围、腰臀比比较有差异(P<0.05)。5、降低空腹胰岛素水平,改善胰岛素抵抗：空腹胰岛素水平及胰岛素敏感指数比较,治疗后两组患者空腹胰岛素均降低,治疗前后比较有差异(P<0.05或P<0.01)；治疗组空腹胰岛素、胰岛素敏感指数的变化与对照组相比,差异有统计学意义(P<0.05)。6、降低血压：治疗后患者收缩压、舒张压均明显下降,与治疗前比较均有显著性差异(P<0.01)；组间比较,治疗组与对照组,无明显区别(P>0.05)。7、安全性指标：治疗组患者血、尿、粪常规及肝肾功能检查均在正常范围。两组均未见不良反应。实验研究：糖脂清组治疗后空腹血糖与模型组比较有显著性差异(p<0.05),与治疗前比较也有显著性差异(p<0.05)。治疗后糖脂清组总胆固醇下降,与治疗前比均有显著性差异(P<0.05),与模型组比也有显著性差异(p<0.05);治疗后糖脂清组大鼠甘油三酯水平显著下降,与模型组比有显著性差异(p<0.05)；治疗后糖脂清组LDL-C水平下降,与模型组比有显著性差异(p<0.05)。糖脂清组大鼠治疗后血清SOD、MDA值与治疗前比较均有显著性差异(P<0.05),与模型组比较也均有显著性差异(P<0.05)。糖脂清组空腹血清胰岛素值与治疗前比较也有显著性差异(P<0.05),与模型组比较有显著性差异(P<0.05)。治疗后糖脂清组炎症细胞因子(CRP、TNF-α)与模型组及吡格列酮组比较,差异有统计学意义(P<0.05)。结论：从初步临床研究来看,糖脂清治疗2型糖尿病合并代谢综合征,可明显改善患者的临床症状；在西医学指标方面,可以降低血糖、糖化血红蛋白,降低血脂水平,改善糖脂代谢及胰岛素抵抗,减轻腹型肥胖,且无肝肾功能损害,治疗本病安全、有效,有广泛的应用前景。糖脂清取得了控制糖尿病和改善代谢综合征的显著治疗效果。但由于条件限制,本研究病例数相对较少,观察指标较简单,需进一步深入研究。实验研究结果提示糖脂清具有降低血糖、血脂,调节糖脂代谢,抗氧化应激,改善胰岛素抵抗和抗炎的作用,但由于条件限制,本研究尚处于整体动物实验水平,观察指标较简单,需进一步深入系统地探讨糖脂清治疗糖尿病的分子机制。更多还原

【Abstract】 Purpose:To discuss the understanding of traditional Chinese medicine about type2diabetes mellitus complicating metabolic syndrome. Through clinical research, using the TangZhiQing Decoction to treat type2diabetes mellitus complicating metabolic syndrome. To observe the therapeutic efficacy of this decoction in treating type2diabetes mellitus complicating metabolic syndrome by the indexes such as clinical symptoms, BMI, Waist-hip ratio, blood pressure, blood glucose, blood lipid levels, FINS, ISI. Then evaluate its curative effect and safety, so as to guide its clinical application. By experiment research, to explore TangZhiQing effects on type2diabetes mellitus complicated with metabolic syndrome model rats blood lipid levels, insulin resistance and inflammatory cytokines and markers of oxidative stress.Methods:A randomized, controlled trial was conducted.The patients of type2diabetes mellitus complicating metabolic syndrome were randomly classified into two groups according to1:1pair matched.On the basic of normal treatment and western medicine,the patients of treated group were treated by Chinese medicine while the patients of controlled group were treated by normal treatment. Observing for3month and four weeks made up of a course of treatment.The observed indexes included curative effect indexes,such as clinical symptoms, BMI, Waist-hip ratio, blood pressure, blood glucose, blood lipid levels, FINS, ISI and so on.The complete data carries on statistics analysis by the SPSS19.0statistics software. Experiment research:in Fed with high fat and high sugar diet contain PTU based on low dose streptozotocin resulting in type2diabetes mellitus complicating metabolic syndrome rat model. After the successful model rats were divided into model group, TangZhiQing group, pioglitazone group and normal control group. After4weeks the rats were observed the following indicators:blood glucose, blood lipid levels, insulin resistance and inflammatory cytokines and markers of oxidative stress.Results:Clinical research:The diagnosis and included type2diabetes mellitus complicating metabolic syndrome patients with60cases.30cases of treated group, while30cases of controlled group. Prior treatment, the gender, age, course of disease of the two groups patients had no differeces.1.Symptoms and signs improvement:the treated group after treatment had a significant improvement. The symptoms improvement of the treated group was better than the controlled group (P<0.01).2.Blood glucose:the FBG, PBG of treated group and controlled group were significantly lower(P<0.01); After treatment, the FBG of the treated group had a significantly difference than controlled group(P<0.01).The PBG of treated group also had a difference than controlled group (P<0.05), The HbAlc of treated group also had a difference than controlled group (P<0.05).3. Improve lipid level:The TG, TC, LDL-C of the two groups were decreased, the HDL-C of them were elevated, compared with pre-treatment there is a remarkable statistically significant (P<0.01). And the treatment group had an advantage over the control group in TG, TC, HDL-C(P<0.01).4.BMI is lower in patients after treatment of two groups, but the difference had no statistically significant (P>0.05), BMI changes of treated group compared with the controlled group had no significant difference (P>0.05).The the WC, WHR of treatment group were decreased, compared with pre-treatment there is statistically significant (P<0.01). The WC, HC. WHR of control group and the HC of treatment group were not decreased after treatment(P>0.05). The descent of WC, WHR in treatment group had a statistically significant compared with control group(P<0.05).5.Reduce fasting insulin levels, improve insulin resistance:compared with fasting insulin levels and insulin sensitivity index, two groups of patients after treatment fasting insulin are reduced (P<0.05or P<0.01), changes in fasting insulin and insulin sensitivity index in the treated group had a difference than controlled group, the difference statistically significant (P<0.05).6.After treatment in patients with systolic blood pressure, diastolic pressure were decreased significantly, compared with before treatment had significant difference (P<0.01); the treatment group and the control group had no significant differences (p>0.05).7.safety index:The routine blood/urine/feces test, and the liver and kidney function tests of treated group were within the normal range.two groups had no unhealthy response.Experiment research:TangZhiQing group after treatment fasting glucose compared with the model groups with significant differences (p<0.05), compared with before treatment had significant difference (p<0.05). After treatment TangZhiQing group total cholesterol declined, compared with before treatment had significant differences (P<0.05), and compared with model group also had significant differences (p<0.05); After treatment TangZhiQing group rats TG significantly declined, compared with the model groups had significant differences(p<0.05); After treatment TangZhiQing group LDL-C level declined, compared with the model groups had significant differences (p<0.05). TangZhiQing group rats serum SOD and MDA after treatment compared with before treatment had significant difference (P<0.05), compared with the model groups also had significant difference (P<0.05). TangZhiQing group of fasting serum insulin level compared with before treatment had significant difference (P<0.05),compared with the model groups with significant differences (P<0.05). TangZhiQing group after treatment of inflammatory cytokines (CRP, and TNF-α)and model groups and comparison of pioglitazone group, statistically significant differences Conclusion:Through the preliminary clinical study, TangZhiQing Decoction has sure curative effected in treating type2diabetes mellitus complicating metabolic syndrome. From the angle of western medicine, it can reduce blood sugar and HbAlc, reduce blood lipid levels, improve glucose and lipid metabolism and insulin resistance, reduce abdominal obesity.And, most important, be safe and effective.It is worth studying deeply and developing further.Remarkable results have been achieved by TangZhiQing Decoction that control diabetes and improve metabolic syndrome.But because of my ability and conditions limited as a overseas student, there were small number of cases and simple observational items in this study. And further inestigations is required. Experimental study results on TangZhiQing Decoction suggest that TangZhiQing Decoction has lower blood sugar, blood lipids, glucose and lipid metabolism regulation, oxidative stress, improve insulin resistance and anti-inflammatory effect, but due to limitations, this research is still in the whole animal level and outcome measures is relatively simple, requires further in-depth and systematic discussion on molecular mechanism of TangZhiQing Decoction in treatment of diabetes mellitus.更多还原