The Clinical Observation Of Dongtiantangmailing Granula On Type 2 Diabetes Mellitus With Lipid Metabolism Disorder And Mechanism Investigation

BackgroundThe morbidity rate of type 2 diabetes mellitus(T2DM) is rising year by year. WHO had reported that the number of global diabetic was one hundred and seventy-five millions in 2000,and would breakthrough three hundreds millions in 2025.China is the second diabetic country in the world,and about thirty millions patients.But the control rate is only twenty-five percent.As we know,longterm glycolipid toxicity can cause injury of blood vessel and many complications.T2DM allway goes with lipid metabolism disorder.Also the lipid metabolism disorder can induce and aggravate insulin resistance(IR),lead to the nonfunction ofβ-cell.So it is very important to investigate the mechanism of T2DM combining with lipid metabolism disorder and give the corresponding treatment.Dongtiantangmailing Granula(DTG) is the sixth new Chinese medicine,which composes of golden thread,manyinflorescenced sweetvetch root,rehmannia dride rhizome,baical skullcap root,turmeric root tuber,ect.It has effect in eliminating dampness and resolving phlegm,benefiting qi and nourishing yin,promoting blood circulation to dissipate blood stasis.Animal experiments showed that DTG had significant effect in adjusting blood glucose and fat metabolism,improving insulin resistance.Compared with metformin,it was more effective in treating experimental rats with T2DM,lipid metabolism disorder and diabetic vessel complications. Foregone clinical trail showed that DTG could remarkablely improve clinical symptoms and reduce the level of fasting blood glucose(FBG),2h postprandial plasma glucose(2hPG),glycosylated hemoglobin(HbA1c),triglyeride(TG),total cholesterol(TC) and low-density lipoprotein(LDL-C).ObjectiveBased on early researches further to observation and evaluate the clinical effect and safety of DTG on T2DM with lipid metabolism disorder.And to investigate the therapeutic machanism through its influence on IR,blood serum level of adiponectin and advanced glycation end products(AGEs).Also to offer theoretical evidence for TCM in treating T2DM with.lipid metabolism disorder.Methods1.The trail was a randomized,double-blind,Tangmaikang granula(TMG) positive controlled clinical trail for DTG to treat T2DM with lipid metabolism disorder (phlegmatic hygrosis endo-stagnant,qi and yin deficiency syndrome in TCM ).40 patients with T2DM complicating with lipid metabolism disorder were randomly divided into to groups.The DTG group were 30 patients,and the TMG group were 10 patients.The research time was from May.2007 to Nov.2007.2.All original selected patients were retained quondam therapeutic drug (sulfonylureas or biguanides) for 2 weeks,if still correspond the standard (7.0≤FBG≤13.0,and(or)11.1≤2hPG≤16.6,HbA_1c≤10%,lipid metabolism disorder based on "Suggestion of Prevention and Treatment for Lipid Metabolism Disorder"in China 1997) would be selected.All sujects were treated for 8 weeks.3.Observe indexes:curative effect indexes include main clinical symptoms and physical signs,vein FBG,2hPG,HbA_1c,TG,TC,HDL-C,LDL-C,vein serum insulin, adiponectin and AGEs.Salty indexes include routine urine,stooll,blood test,liver and kidney function,EKG,ect.The indexes above were tested befor and after 8 weeks' treatment.Durante the trail,the patients were visited every two weeks.The changes of clinical symptoms were recorded and the FBG,2hPG were tested each visitation. 4.Assay methodes:FBG,2hPG and blood fat were tested by holo-automatic haemato-biochemistry analysator of Nanfang Hospital Clinical Laboratory Department.HbA1c was tested by stratography.Serum insulin,adiponectin,advanced glycation end products were tested by ELISA.5.Statistical analysis:The medical statistical analysis software SPSS13.0 was used to analyze the results.Two sets of data used hierarchical rank and testing,all other statistical tests used both tests.Each different treatment group for treatment of measurement data used mean±standard deviation for descriptive statistics.Used paired t tests to compare differences before and after treatment.Different treatment group of each treatment used frequency count data(composition ratio) for statistical description.(1) off analysis:the two groups and the total loss rate of adverse events used of the X² test.(2)based on the value of the analysis:used ANOVA or X2 test to compare demographic data and measure the balance of the two groups.(3) Security Analysis:used the X² test to compare two groups the incidence of adverse events and a list of the tests describe in the adverse events.Results1.The number of cases under the pilot 40 cases,35 cases of the actual finish,one of the pilot group of 27 cases,8 cases of the control group.2.Clinical observation:The difference among sex,age,course of Disease,vital signs,complication,familial inheritance,treat history,Integration of TCM symptome was not significant between the DTG group and the TMG group,the two groups were comparable(P＞0.05).by rank sum test,The results showed that The difference among FBG,2hPG,HbA1c,lipids was no significant difference between the two groups.The clinical curative effect between DTG group and TMG group is comparable(P＞0.05),but,The clinical curative effect of TCM between two groups is significant(Z=-3.80,P=0.0001).moreover,The difference of Integration of TCM Syndrome was significant before and after treating with DTG or TMG between DTG group and TMG group(P＜0.05).DTG and TMG can improve the symptom of TCM remakbaly before and after treating.DTG can improve the symptom of TCM better than TMG.In different time periods and the difference before and after treatment FBG,2hPG,HbA1c,lipids was no significant(P＞0.05) At the end of 8 weeks' treatment,in the DTG group and the TMG group The difference among FBG, 2hPG,HbA1c,TG,Integration of TCM symptome was significantly,but,The difference among TC,LDL-C,HDL-C was no significant.DTG and TMG can reduce the level of FBG,2hPG,HbA1c,TG,and improve the symptom of TCM remakbaly before and after treating.However,in the reduction of TC,LDL-C,HDL-C value was not obvious.Security,once the course of treatment or the number of cases to have a bad case of the DTG group 1 cases,the TMG group was 0 cases.Two groups the incidence of adverse events were 3.33%and 0%,there was no significant difference (P=1.0000).The adverse events were judged and probably unrelated to study medication,adverse events after the end of the trial have been eased.Two groups of safty indexes include routine urine,stooll,blood test,liver and kidney,EKG,ect.the difference did not achieve statistical significance.3.Experimental research:The difference among insulin resistance,serum adiponectin advanced glycation end products was significant in the DTG group,the difference between the two groups showed no significant difference(P＞0.05).the DTG group and the TMG group can improve the degree of insulin resistance,it is similar to the mechanism of the two drugs.Conclusion1.DTG has good Long-Term safety and efficacy in Patients of T2DM with lipid metabolism disorder(phlegmatic hygrosis endo-stagnant,qi and yin deficiency syndrome in TCM ).â…¢clinical trail show that DTG could remarkablely improve clinical symptoms of TCM and reduce the level of FBG,2hPG,HbA1c,TG.2.DTG can ameliorate insulin resistance of T2DM with lipid metabolism disorder,the increase of insulin sensitivity probably by improving glucose with lipid metabolism and increasing serum adiponectin level;And,By controlling advanced glycation end products,to delay the occurrence or progression of diabetic vascular complications.