Clinical Investigation Of Supplemented Banxiaxiexin Decoction On Glucose Control In Patients With Type 2 Diabetes And Spleen Deficiency And Stomach Heat Syndrome

With the rapid development of science and technology,the understanding of Chinese medicine has gone beyond the limitation of symptom differentiation which may delay the diagnosis when it's asymptomatic.Many traditional Chinese Medicine?TCM?experts have reached an agreement that disharmony between Spleen and Stomach is the core pathogenesis in type 2 diabetes mellitus?T2DM?.While BanxiaxiexinDecoction?BXXD?originated from Treatise on Febrile and Miscellaneous Diseases specialized in harmonization between Spleen and Stomach has been widely used in the TCM field as a fundamental formula to realize better blood glucose control and maintain good metabolic level other than single symptom alleviation.However,there is no existed systematic review to review its effect with regard to glucose control.Hence a systematic review is carried out in the first section of this thesis,in which it's found that the original research is low in methodological design and other defectsexist that may cause unwanted bias.Therefore,a quality research is needed to obtain a reliable result.Blood variability metrics are the emerging indices to describe precise control of blood glucose which is necessary for ideal glucose control target which is proved to be the basis for reducing incidence of diabetic cardiovascular complications.However,few TCM researches focused on the influence of TCM on glycemicfluctuation.Hence in the second part a randomized clinical trial was designed toobserve the clinical effects of BXXD in combination with intensive insulin care with contrast to intensive insulin care in two centers,with main focus on glycemicfluctuation metrics with both SMBG method and FGM method.Section One.Effect of Chinese Herbal Medicine Banxiaxiexin Decoction on Glycemic Control in Patients with Type 2 Diabetes:A Systematic Review of Randomized Controlled TrialsObjective:To systematically evaluate the clinical effects of BXXD for T2DM by conducting literature reviews in databases for randomized controlled trials?RCTs?.Methods:Electronic databases were searched until December 2019.No language limitations were applied.We included RCTs using exact BXXD or BXXD modification for T2DM.No restriction for the control group except non-medication therapy such as acupuncture and moxibustion.The primary outcomes are fasting blood glucose?FBG?,glycated hemoglobin?Hb A₁c?and 2-hour postprandial blood glucose?2h PBG?.Secondary outcomes include clinical effective rate based on descriptions in guidelines for the clinical research of Chinese medicine.Data extraction,analyses and quality assessment were conducted according to the Cochrane review standards with the help of Rev Man 5.3.Results:Altogether 8 randomized controlled trials were included in this meta-analysis,all of which were published in Chinese from 2013 to 2019.A total of 1016 patients with T2DM were aged from 33 to 77 years old,with treatment course ranging from newly diagnosed diabetes to 15 years of onset.?1?Fasting blood glucose?FBG?:FBG was analyzed in 8 literature,and the treatment course was from 1 month to 3 months respectively.The results of meta-analysisshowed that the experimental group of BXXD combined with conventional western medicine was superior to the control group of western medicine alone.?2?2-hour postprandial blood glucose:6 literature reported postprandial blood glucose changes after treatment,and meta-analysis showed that the experimental group ofBXXD combined with conventional western medicine treatment was superior to the control group treated with western medicine alone.?3?Glycated hemoglobin:6 literature have analyzed the effect of traditional Chinese medicine on patients'glycated hemoglobin,and the results show that the experimental group of BXXD combined with conventional western medicine treatment issuperior to the control group of western medicine treatment alone.?4?Clinical efficacy:there were 4 literature that analyzed the effect of clinicalefficacy after medication,and the results showed that the experimental group was better than the control group in terms of clinical efficacy.?5?Safety:no adverse reactions occurred in the above studies,and no adverse events were recorded.Conclusions:BXXD combined with conventional medicine is superior to conventional medicine alone in terms of blood glucose control and symptom alleviation.However,due to the low methodological quality of included studies as well as the limit of short observation time,the findings derived from this review should be explained with caution.Thereby,well-designed,large-scale,and high-quality randomized controlled clinical trials are needed in future research.Section Two.Clinical Investigation of Supplemented Banxiaxiexin Decoction on Glucose Fluctuation in Patients with Type 2 Diabetes and Spleen Deficiency and Stomach Heat SyndromeObjective:To compare the effects of group A?combined use of supplemented BXXD and intensive insulin care?and group B?intensive insulin care?with regard to clinical effective rate and glycemic fluctuation metrics with the use of traditional SMBG?self-monitoring blood glucose?method by which the finger is stuck 7 times a day or Flash Glucose Monitoring method?FGM?.Methods:A total of 96 patients with T2DM?Spleen-deficiency and Stomach-heat Syndrome?who met the inclusion criteria were enrolled in a randomized,double-centered prosperous controlled study.The patients were randomly assigned to group A?combined use of supplemented BXXD and intensive insulin care?and group B?intensive insulin care?with 48 cases in each group.All groups received basic treatment of diabetes,including diabetes health education,diabetes diet control guidance,exercise advice and SMBG provided by the research team.All the patients received insulin intensive care including insulin aspart three times a day shortly before meal and insulin detemir before bedtime.The intensive insulin care lasted for14 days with adjustment of insulin dosage in accordance with experts'consensus.For financial limit of the research,only 18 people in each group received FGM monitoring which last for 14 days.All the patients were examined of plasma fasting glucose?FPG?,2-hours postprandial glucose?2h PG?,HBA₁c and Fasting Insulin ?Fins?and other biochemical indices before the onset of the drug administration.The time?day?when the glycemic goal?4.4-7.0mmol/L for FBG,and less than 10mmol/L for 2h BG?was reached was recorded and the corresponding total dosage of insulin on that day as well as the insulin total dosage on the 14^thday were recorded and compared.The insulin intensive care was ceased after two weeks and TCM decoction was stopped,too.All the patients were tested of their FPG,2h PG,Fins and the 7-point finger-stick glucose level before and after treatment.Patients were treated with conventional methods decided by their attending doctors then and they were followed up for another 10 weeks.They were suggested to check the HBA₁c at the end of the 12th week and their 7-point finger-stick glucose levels were recorded,too.The usage of antihyperglycemic medications were noted at that time also which was divided into 4 classes:continued intensive insulin therapy,two time injection of insulin with or without combination of oral agents,one-time use of insulin with or without oral medication,and oral antihyperglycemic agents alone.Results:1. Baseline comparison:A total of 10 subjects in the two centers dropped out for various reasons,and the number of people who completed the study was 86,with 43cases in each group.The two groups were comparable in terms of age,course of disease,BMI,blood glucose,Fins,HOMA-IR,liver and kidney function,and TCM syndrome scores before treatment.2. Efficacy comparison:?1?Comparison of TCM syndrome score:After treatment,total score of the two groups decreased while sore of group A was significantly lower than that of group B after the treatment and the difference was statistically significant?P<0.05?,indicating that group A had more advantages in improving the symptoms of patients than group B.In terms of single symptom remission,despite"loose stool"which did not differ between groups,scores of conditions such as epigastric fullness,poor appetite,fatigue,dry and bitter mouth,retching hiccups,dizziness and heavy limbs,extreme desire to having food together with decreased intake of food are different between groups were all lower in group A,indicating that group A was better than group B in symptom alleviation.?2?Comparison of clinical effectiveness:The effective rates of group A and group B were 86.05%and 67.44%,respectively.After treatment,the difference in the total clinical effectiveness of the two groups was statistically significant,indicating that the efficacy of group A was better than that of the group B.?3?Glucose control and insulin dosage:The FPG and 2h PG dropped after treatment and the difference was statistically significant for each group indicating that both treatments were effective.However,the FPG and 2h PG differences after group was of no statistical difference indicating that 2 weeks combination of hers did no better in glucose control.The amount of insulin difference between the day reaching the glycemic target and the 14th day differed in group A and group B,indicating that group A can help better reducing the insulin dosage when it reached the glucose target.?4?Metrics of blood glucose fluctuation derived from finger-stick blood glucose test:The index of finger blood glucose fluctuation in the two groups decreased after treatment,and the difference was statistically significant.In addition,SDBG,PPGE and LAGE in group A after the treatment were all better than that in group B,indicating that the combination of traditional Chinese and intensive insulin therapy is better in reducing blood fluctuation.?5?Metrics of blood glucose fluctuation derived from FGM data:2 weeks after the treatment,there is no statistical difference between two groups with regard to percentage of time in range?TIR%?,but differences exist with regard to percentage of time below the range?TBR%?and hypoglycemic events and classical metrics of glycemic variability such as MAGE and MODD,indicating that group A is better in reducing glucose variability.?6?Index of insulin resistance:After 2 weeks of treatment,HOMA-IR index of both groups decreased,and HOMA-IR index of group A after treatment was lower than that of group B,indicating that integrated Chinese and western medicine has more advantages in reducing insulin resistance.?7?Follow-up at the end of the 12th week:It was found that Hb A1c in both groups was significantly lower than that before the treatment,and the difference was statistically significant?P<0.01?in each group,indicating that after fundamental treatment by western medicine,the patients'hyperglycemia status were effectively corrected,but the difference between groups was not statistically significant.At the same time,through follow-up,it was also found that short-term combination of traditional Chinese medicine seemed to have lasting effect to glycemic control since it dropped down the PPGE at the 12th week when TCM was ceased and the combination of traditional Chinese medicine could reduce the number of insulin injections and improve the convenience of administration for patients.3. Safety comparison:During the treatment,no adverse events such as FGM scan breakage or allergic reactions.After 12 weeks of follow-up,2 cases of mild hypoglycemia occurred in group A and 5 cases of mild hypoglycemia occurred in group B.The number of cases of hypoglycemia in the treatment group was less than that in the control group,but the incidence of hypoglycemia events was not statistically significant.No other adverse events were reported in this period.Conclusion:Combined use of supplemented BXXD with insulin intensive care can be beneficial with regard to reducing blood glucose fluctuation indices such as SDBG,LAGE,PPGE,MAGE and MODD,decreasing insulin resistance,reducing hypoglycemic event and hypoglycemic time,lowering down the dosage of insulin and alleviation of clinical symptoms such as epi-gastric fullness or distention,dry and bitter mouth,poor appetite,fatigue,dry and bitter mouth,retching hiccups,dizziness and heavy limbs,extreme desire to having food together with decreased intake of food.The advantage of supplemented BXXD with regard to blood glucose control may lie in its special effect on blood glucose excursion.Therefore,supplemented BXXD can definitely facilitate with insulin intensive therapy in T2DM patients to avoid hypoglycemic events,gain better patient satisfactory results.It can be promoted further in the after clinical practice.