探讨2型糖尿病肠道湿热证证候特点及葛根芩连汤干预机制.ppt

1、The efficacy of a Chinese herbal formula GQD on type 2 diabetes and its mechanism,Dr. Linhua Zhao Guang anmen Hospital,China Academy of Chinese Medical Science Beijing, China,Melonzhao (Dr. Linhua Zhao),Doctor of traditional Chinese Medicine in Endocrinology departmentResearcher of Molecular Biology

2、 Research LaboratoryDose-response relationship study of Chinese Medicine Committee of World Federation of Chinese Medicine Societies (Secretary)Dose-response relationship study of Chinese Medicine Branch of Chinese Association of Chinese Medicine (Secretary)Chinese medicine research and Promotion As

3、sociation of diabetes mellitus (permanent member),2,The main research area is the clinical and basic research of diabetes mellitus and diabetic complications. As the project leader and backbone，I hosted and participated 14 national and city level scientific research projects.A total of 45 academic p

4、apers were published and 16 of them were included by SCI, and 8 papers were as co-author of first or correspondence author. The highest impact factor of one of the papers is 9.302, which is the first international clinical trial about the intestinal flora structure changes and the dose-response rela

5、tions of traditional Chinese medicine on type 2 diabetes.,Diabetes mellitus is one of the most important chronic diseases that threaten the health of human beings in the world. According to the International Diabetes Federation (IDF) of the latest statistics in 2015, the prevalence of diabetes in ad

6、ults aged 20-79 years old is 8.8%, the number of patients has reached 415 million.,There are many reports of diabetes treatment recorded in the ancient classic medical books.,Traditional Chinese medicine has a long history in the treatment of diabetes, and the effect is exact.,What can Traditional C

7、hinese Medicine do on Prevention and Treatment of Diabetes?,Primary prevention,Secondary prevention,Tertiary prevention,1. Reduce the conversion of DM,2. Lower glucose independentlyDelay the development of complications,3. Treat the complications Decrease the disability and fatality,5,6,Whats GQD? D

8、iarrhea DiabetesA standardized berberine-containing Chinese herbal formula, Gegen Qinlian Decoction (GQD) has been a treatment for diarrhea in Shang Han Lun since the East Han Dynasty. Its use was recorded by the prestigious physician Zhongjing Zhang (150-219 AD). Subsequently, GQD has been reported

9、 to have potentially beneficial effects in the treatment of diabetes in animal trials, as well as in some clinical observations.,7,First, researchers found GQD significantly reduced fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) in streptozotocin (STZ) and high fat diet-induced diabetic

10、 SD rats, and the serum of SD rats that received GQD enhanced glucose consumption in 3T3-L1 adipocytes. T2D patients treated with a high dose of modified GQD twice daily for 3 months showed a reduction in HbA1c of 1.79% from the initial level of 9.2%. This decrease was significantly different from t

11、hat of patients receiving a low dose treatment,Tong et al., 2011. Zhan C H.et al.Phytomedicine,2013.,8,Supported by the project “Dose-Effect Relationship Study of Chinese Classical Formulas”,Study object：224 new diagnosed patients with Type 2 diabetesStudy method：multicentered, randomized, double-bl

12、inded, placebo-controlled clinical trialStudy design：high dose, moderate dose, low dose, placeboPrimary efficacy outcomes：HbA1c, the composition of gut microbiotaSecondary efficacy outcomes：FBG, 2h-PBG, TCM symptoms score, lipid levels, body mass index,DIABETES,RCT of GQD on type 2 diabetes,Reducing

13、 HbA1C significantly and it is dose-dependent（HD, MD, LD and placebo reduce HbA1C is respectively 0.95%、0.79%、0.28% ，0.31%）.Real-time quantitative PCR confirmed that the Chinese herbal formula significantly enriched Faecalibacterium prausnitzii, and Pseudobutyrivibrio were significantly decreased.,9

14、,DIABETES,RCT of GQD on type 2 diabetes and its mechanism,Impact of GQD on plasma adiponecin, Tumor Necrosis Factor-(TNF-) and serum amyloid A protein (SAA),10,DIABETES,GQD on type 2 diabetes,11,To our knowledge, this study is the first registered clinical trial to evaluate the dose-dependent effica

15、cy and safety of a Chinese herbal decoction following a randomized, double-blinded and placebo-controlled design.,In patients with type 2 diabetes, there is a moderate imbalance of intestinal flora,Faecali and many kinds of butyrate bacteria reduced; sulfate reducing bacteria of opportunity pathogen

16、ic bacteria increased.,Qin J., et al. Nature,2012, The intestinal flora changes in high fat diet :probiotics reduce and harmful bacteria increase. Harmful bacteria damage the intestinal mucosa, intestinal mucosal barrier function is reduced, the level of blood endotoxin increased. low levels of chro

17、nic inflammation is induced; The insulin resistance is triggered and which leading to disorder of glucose metabolism.,Cani P D., et al. Curr Pharm Design, 2009,The development of intestinal flora in the development of type 2 diabetes mellitus,The microflora structure of Gegenqinlian decoction can im

18、prove the intestinal damp heat syndrome of diabetes,Short chain fatty acid production of Faecali and Bacillus were significantly enriched, and showed significant negative correlation with glycosylated hemoglobin, fasting blood glucose.,15,Through the study of network pharmacology of Gegenqinlian Dec

19、oction effective components were explored.,Consistent with the dose-dependent manner of T2D amelioration, GQD also exerted a dose-dependent modulation on the gut microbiota, suggesting a strong association between the modulation of gut microbiota and T2D alleviation. Our study suggests that gut micr

20、obiota might be involved in the effect of a widely used TCM formula, GQD.,16,The study is still continuing, furthermore, we will do some animal study to confirm whether changes of gut microbiota by GQD directly contribute to the improvement of glucose homeostasis.,17,Guang anmen HospitalChina Academy of Chinese Medical ScienceRoom 534 in Administration BuildingNo.5 Beixiange Street, Xicheng District, Beijing 100059, China Telephone: 86-010-88001812E-Mail: ,Thanks for your attention!,