Evaluation Of Clinical Evidence And Experimental Study On Pre-diabetes With TaVNS

ObjectiveThis study intends to explore and supplement the evidence of transcutanous auricular vagus nerve stimulation(taVNS)in prediabetes based on the evaluation of the relevant evidence at all levels of evidence.The evidence at all levels includes the recommendations in the relevant clinical practice guidelines,systematic reviews,randomized controlled trials(RCTs)and so on.It provides reference to the development of the next step multi-center large sample RCTs,the production of the high quality of acupuncture clinical research evidence including RCT and systemetic reviews and the appearance of the contents of acupuncture treating prediabetes in clinical practice guidelines.At the same time,it provides a paradigm for evidence-based acupuncture research.Methods1.To systematic review the clinical practice guidelines(CPGs)associated with prediabetes treated by acupuncture,including acupuncture guidelines and diabetes guidelines.Using the international general methodological quality assessment tools-AGREEII and report quality assessment tools-the RIGHT to evaluate CPGs.2.Summarizing and analyzing the recommendations of acupuncture treatment of prediabetes in CPGs.3.Conducting systematic reviews and meta-analysis to compare acupuncture curative effect of different kinds of treatments for patients with prediabetes,including security,compliance and other indicators.Using subgroup analysis to compare the curative effect of specific acupuncture treatments.Figuring out the sources of heterogeneity by subgroup analysis,sensitivity analysis,etc.4.Conducting the methodological quality and reporting quality evaluation of different types of acupuncture treatments for patients with prediabetes randomized controlled trials(RCTs)by using the Cochrane Risk of bias tool and the CONSORT joint STRICTA checklist.5.Conducting mechanism research of taVNS treating prediabetes and elaborating the functions of adjusting the IGT model rats sugar metabolism and insulin receptor expression by taVNS.Results1.The methodology and reporting quality of the CPGs related to acupuncture intervening prediabetes,including acupuncture guidelines and diabetes guidelines are generally low,remains to be further improved.2.The CPGs of diabetes developed by different countries and organizations worldwide did not include acupuncture as recommendations.A few CPGs of diabetes developed by China mentioned in the treatment of traditional Chinese medicine(including acupuncture),but did not mention the specific acupuncture interventions and the information such as dosage,treatment course.3.The fasting blood/plasma glucose(FBG/FPG)after treatment,2 h postprandial blood glucose,glycosylated hemoglobin(HbA1c),serum total cholesterol(TC),Triglyceride(TG)and Body Mass Index(BMI)of the experimental group(acupuncture)were superior to control group.The auricular acupuncture is best for reducing FBG/FPG,TC and TG.Magnetic circle needle,Ping Heng Zhen and other special acupuncture types maybe have better effects on OGTT 2h and HbAlc.Mono-acupuncture is good for lowering BMI.The differences mentioned above were statistically significant.The adverse effects are low in the process of the treatment except 1 case appeared dizziness,3 cases of diarrhea(cannot be ruled out whether associated with traditional Chinese medicine combined treatment),and no obvious adverse events,operation safety,patient compliance is higher.4.Included RCTs of acupuncture treatment of prediabetes’methodological quality and reporting quality are low.In general,a RCT-taVNS treating Impaired glucose tolerance(IGT)is considered to be the highest evidence currently in three dimensions including the main effects of index value,experimental design methodology and reporting quality.5.After 4 weeks of taVNS treatment,the body weight of taVNS group rats showed a lower level than model group rats.Fasting plasma glucose in taVNS group rats showed a lower level than model group rats(t=2.1923,P=0.0435)and tnVNS group rats(t=2.3636,P=0.0311).Oral sugar tolerance test 2h of taVNS group rats decreased which had statistical significance compared with model group rats(t=-4.6295,P=0.0003)and tnVNS group rats(t=-2.5059,P=0.0234).Versus model and tnVNS group rats,taVNS increased plasma fasting insulin,decreased glucagon and glycosylated hemoglobin concentration.Western blot analysis and Immunohistochemical staining showed that the expression of insulin receptor in hypothalamus and liver was upregulated in taVNS group rats.ConclusionWe summarized and supplemented evidence at all levels focuses on taVNS to intervene prediabetes,in order to provide references to the development of the next step multi-center large sample randomized clinical trials,the production of the high quality of acupuncture clinical research evidence including RCT and systemetic reviews and the appearance of the contents of acupuncture treating prediabetes in clinical practice guidelines.At the same time,it provides a paradigm for evidence-based acupuncture research.The future research may focus on resolving the evidence gap between clinical practice and clinical practice guidelines of acupuncture and moxibustion in order to put the superior diseases of acupuncture and moxibustion into clinical practice guidelines at an early date.