【作者】 黄凤；

【导师】 王宏才；

【作者基本信息】 中国中医科学院 ， 针灸推拿学， 2011， 硕士

【摘要】 1研究目的采用单盲、同期随机对照试验对耳迷走神经刺激干预糖耐量受损(Impaired Glucose Torlarece,IGT)患者进行临床疗效和安全性评价,为临床实践提供研究证据,并为后期研究打下基础。2研究方法2.1诊断标准依据1999年世界卫生组织(WHO)与国际糖尿病联盟(IDF)糖尿病专家委员会对IGT的定义：空腹血糖(FPG)<7.0 mmol/L(126 mg/dl),且2小时后75 g口服葡萄糖耐量血糖(2hPG)≥7.8 mmol/L(140 mg/dl),但<11.1mmol/L(200 mg/dl)进行诊断,同时制定严格的纳入、排除、剔除、脱落标准。2.2研究对象2.2.1分组：将符合纳入标准的72例受试者,随机分为2组,同期选取30例作为空白对照,分组如下：耳迷走神经刺激组(Auricular Transcutdneous Vagus Nerve Stimulation, ATVNS):36例,刺激耳甲区“迷走穴”。耳非迷走神经刺激组(Auricular Non Vagus Nerve,ANVNS):36例,刺激外耳缘中点非迷走神经分布区。空白对照组(Blank Control,BC):30例,不采取任何治疗措施。2.2.2治疗方法：运用耳针式迷走神经刺激器(华佗牌耳迷走神经刺激仪,型号TENS-200,苏州医疗用品厂有限公司生产)进行治疗。输出电流1mA,脉冲频率20 Hz,脉冲宽度≤1ms,强度以忍受而不产生疼痛为度；刺激时间为每次20 min,一天2次。共治疗12周。2.3观察指标及时点记录受试者年龄、性别等基本资料,记录各组入组前、治疗12周结束后患者体重指数(Body Mass Index, BMI)、FPG、2hPG、糖化血红蛋白(Glycated Hemoglobin,HbAlc),及治疗(观察)第6周FPG.2hPG.2.4统计及数据分析应用SPSS软件进行统计分析。根据本研究中的临床资料特点,依据相关统计学原理对受试者数据进行统计。计数资料采用x2检验；等级资料采用秩和检验；符合正态分布的计量资料采用方差分析,不符合正态分布的计量资料先进行正态转换,经转换符合正态分布的数据采用参数检验；经转换仍不符合正态分布的数据采用秩和检验。检验水准α=0.05。3试验结果共纳入102名IGT受试者,治疗过程中脱落2人,共100例受试者完成试验。3.1降糖效果分析3.1.1组间比较三组受试者治疗(观察)第6周、第12周后FPG疗效差值比较,ATVNS[分别为(0.32±0.65)；(0.48±0.58)mmol/L]较BC[分别为(-0.19±0.70)；(-0.42±1.11)mmol/L]明显下降(P<0.01)；第12周后ANVNS(0.09±0.81 mmol/ L)FPG疗效差值较BC下降明显(P<0.01)。三组受试者治疗(观察)第6周、第12周后2hPG疗效差值比较,ATVNS[分别为(2.39±1.87)；(2.19±1.48)mmol/L]、ANVNS[分别为(1.10±1.73)；(1.16±1.56)mmol/L]较BC均有明显下降(P<0.01),ATVNS下降较ANVNS明显(P<0.05)。三组受试者第12周后HbA1c疗效差值比较,ATVNS(0.17±0.34%)下降较BC(-0.14±0.37%)明显(P<0.01).ANVNS(0.13±0.49%)下降较BC明显(P<0.05)。3.1.2组内比较ATVNS:第6周、12周FPG[分别为(5.89±0.77)；(5.73±0.63)mmol/L]、2hPG[分别为(7.32±1.76)；(7.52±1.35)mmol/L],第12周HbAlc(6.15±0.44%)与入组前[分别为(6.21±0.60)；(9.71±1.14)mmol/L,6.32±0.53％]平均水平比较均有明显下降(P<0.01)。ANVNS:第6周、12周2hPG[分别为(8.01±1.58)；(7.95±1.44)mmol/L]与入组前(9.11±1.21mmol/L)平均水平比较有明显下降(P<0.01),治疗结束后2hPG平均值仍大于正常值7.8 mmol/L.BC：第12周FPG(6.93±1.22 mmol/L).HbAlc(6.30±0.58%)与入组前[分别为(6.44±0.27mmol/L)；(6.16±0.35%)]比较,有升高趋势(P<0.05)。3.1.3频数变化分析治疗结束后ATVNS的FPG(25例)、2hPG(34例)下降例数较BC(分别为10例、11例)多(P<0.05)。刺激耳迷走神经对降低FPG的总有效率为85.71%,降低2hPG的总有效率为82.85%。刺激非耳迷走神经对降低FPG的总有效率为62.86%,降低2hPG的总有效率为80.00%。3.2 BMI结果3.2.1组间比较治疗12周后,三组受试者BMI疗效差值组间两两比较没有明显差异(P>0.05)。3.3.2组内比较12周后,ATVNS受试者BMI(23.90±3.22 Kg/m2)平均水平与入组前(24.40±3.42kg/m2)比较下降明显(P<0.01)；ANVNS受试者BMI(23.87±2.73 Kg/m2)平均水平与入组前(24.12±2.73 Kg/m2)比较有所下降(P<0.05)。3.3中医症状评分及证型分析3.3.1组间比较治疗(观察)结束后,三组受试者中医症状评分疗效差值组间比较,ATVNS(5.11±8.71)、ANVNS(5.77±7.66)下降较BC(1.43±5.10)明显(P<0.05)。三组受试者治疗(观察)结束后正常体质比例组间比较,ATVNS(12例)正常率较BC(2例)明显(P<0.01)；治疗(观察)结束后ATVNS(12例)正常体质转归率明显大于入组前(1例)(P<0.05)。3.3.2组内比较治疗(观察)12周后ATVNS(13.83±11.82).ANVNS(14.11±9.38)受试者中医症状评分平均水平较入组前[分别为(18.94±10.90)；(19.89±12.19)]明显降低(P<0.01)；3.4安全性指标分析治疗(观察)结束后,ATVNS(118.60±13.53 mmHg)收缩压异常比例较入组前(123.66±14.34 mmHg)有所降低(P<0.05。各组顺利完成本课题的受试者,在治疗(观察)前、后其心率、呼吸频率、体温均无显著变化,差异无统计学意义(P>0.05)。治疗过程中,有一例受试者因头痛退出,有一例受试者因不能坚持治疗脱失。少数几例受试者有高血压病史,安全评价为2级安全,不做处理。4结论1)刺激耳迷走神经可降低血糖、糖化血红蛋白、BMI、收缩压,以及改善症状,尤其对降低餐后血糖疗效显著。2)刺激耳非迷走神经穴位区亦有降低餐后血糖、糖化血红蛋白,改善症状的效果。3)刺激耳迷走神经降低餐后血糖的效果优于刺激耳非迷走神经；降低血糖、糖化血红蛋白,以及改善症状的效果优于空白对照组。4)空白对照组在没有任何实施干预措施的情况下,血糖、糖化血红蛋白明显升高。5)耳迷走神经刺激是一种改善糖代谢、预防糖尿病的安全有效的新方法。更多还原

【Abstract】 1. ObjectiveTo evaluate the effectiveness and safety of intervention for IGT patients by auricular vagus nerve stimulation through a single-blind and randomized controlled trial, thereby providing the evidence and basis for the clinical practice and future research concurrently.2. Method2.1 Diagnosis CriteriaThe definition of IGT by the expert committee of the World Health Organization (WHO) and the International Diabetes Federation (IDF) in 1999:fasting plasma glucose (FPG)<7.0 mmol/L (126 mg/dl); and 2 hours after ingesting 75g of glucose, the Oral Glucose Tolerance Test (OGTT) resulting in plasma glucose (2hPG) =7.8mmol/L(140 mg/dl) but<11.1mmol/L(200 mg/dl). Inclusive, exclusive, eliminative, as well as rejective criteria were strictly formulated.2.2 Grouping and Treatment Method2.2.1 Grouping:72 IGT subjects who fulfilled the inclusive criteria were randomly divided into two groups, while we enrolled 30 subjects into blank control group simultaneously.Auricular vagus nerve stimulation (ATVNS):36 cases, stimulating the auricular concha vagus acupoints by electric acupuncture;Auricular non-vagus nerve stimulation (ANVNS):36 cases, stimulating the auricular non-vagus nerve area on the middle point(s) of auricle edge by electric acupuncture.Blank control (BC):30 cases with no treatments.2.2.2 Treatment MethodsThe treatment lasts for 12 weeks, twice a day,20 minutes each time, by using the auricular vagus stimulator (Huatuo Auricular Vagus Stimulator, model TENS-200, produced by Suzhou Medical Products Factory Ltd. Co.) with 1mA output currency, 20Hz pulse frequency and=1ms pulse width, slightly adjusted individually according to the pain tolerance of each subject.2.3 Observation Indexes and Time Points2.3.1 Indexes of Clinical Therapeutic Evaluation Recorded the age, gender and other basic data of the subjects, examined the BMI, FPG,2hPG and HbAlc individually, before and after the 12-week treatment, and the FPG and 2hPG at the 6th weeks as well.2.3.2 Safety IndexesBlood pressure, respiration frequency, heart rate, body temperature.2.4 Data Process and Statistical AnalysisDatabase establishment:A database, for recording and managing the electronic data, made by Microsoft Excel, would be used for the final statistical analysis. Input the same data into two databases for accuracy comparison and corrected them by referring to the original data in CRF if there were discrepancies.3 RESULTSThere were 102 IGT subjects enrolled at the beginning and 2 people dropped off during the treatment. Finally 100 subjects finished the treatment.3.1 Blood Glucose3.1.1 Comparison among groupsThe different effect values of FPG, in ATVNS [(0.32±0.65); (0.48±0.58) mmol/L, respectively] decreased more markedly than that of BC[(-0.19±0.70); (-0.42±1.11) mmol/L, respectively] (P<0.01) before and after the 6week and 12week treatments. ANVNS(0.09±0.81 mmol/L) decreased more markedly than that in BC (P< 0.01) before and after the 12week treatments.The different effect values of 2hPG in ATVNS [(2.39±1.87); (2.19±1.48) mmol/L, respectively]and ANVNS [(1.10±1.73); (1.16±1.56) mmol/L, respectively] decreased more obviously than those in BC (P<0.01), ATVNS decreased more obviously than that in ANVNS (P<0.05) before and after the 6w and 12w treatments respectively.The different effect values of HbAlc in ATVNS (0.17±0.34%) and ANVNS (0.13±0.49%) decreased more obviously than those in BC (-0.14±0.37%) (P< 0.01 and P<0.05 respectively) before and after the 12w treatments.3.1.2 Comparison within groupsATVNS:It showed significant decrease(P<0.01)by comparing the mean level of the FPG and 2hPG [(6.21±0.60); (9.71±1.14) mmol/L, respectively] before, during and after the 12week treatments [(5.89±0.77),(5.73±0.63); (7.32±1.76),(7.52±1.35) mmol/L, respectively]; The HbAlc (6.32±0.53%) shows the same after the 12week treatments(6.15±0.44%).ANVNS:It showed significant decrease(P<0.01)by comparing the mean level of the 2hPG (9.11±1.21 mmol/L) both before and after the 6w and 12w treatments [(8.01±1.58); (7.95±1.44) mmol/L], but the mean value, which the normal value is 7.8mmol/L. BC:It showed a rising trend (P>0.05) by comparing the mean level of the FPG (6.44±0.27 mmol/L) and HbAlc (6.16±0.35%) before and after the 12week treatments(6.93±1.22 mmol/L); (6.30±0.58%).3.1.3 Frequency variationIt shows statistical significance (P<0.05) by comparing the frequency variation of FPG (25 cases) and 2hPG(34 cases) after the 12week treatments between ATVNS to BC (10; 11 cases).The effective rate of reducing FPG and 2hPG by stimulating the auricular vagus nerve and non-vagus were 85.71%,82.85% and 62.86%,80.00% respectively.3.2 BMI3.2.1 Comparison among groupsIt showed no statistical significance (P>0.05) by comparing the different effect values of BMI in all groups after the 12w treatments.3.2.2 Comparison within groupsIt showed no statistical significance (P<0.01 and P<0.05, respectively) by comparing the mean level of the BMI in ATVNS (24.40±3.42 Kg/m2) and ANVNS (24.12±2.73 Kg/m2) before and after the 12week treatments [(23.90±3.22); (23.87±2.73) Kg/m2, respectively].3.3 TCM symptoms score and syndrome types3.3.1 Comparison among groupsThe decrease of the different effect values of TCM symptoms score in ATVNS (5.11±8.71) and ANVNS (5.77±7.66) were more obvious than those in BC (1.43± 5.10) (P<0.05) after the 12w treatments.After the 12w treatments, it shows ATVNS (12 cases) was more obvious than BC (2 cases) (P<0.01)through the comparison of the normal TCM physique ratio among all groups, and it shows significant conversion of the normal TCM physique in ATVNS (1 cases) (P<0.05) after the 12w treatments (12 cases).3.3.2 Comparison within groupIt proves the significant effects on symptoms improving by stimulating the auricular concha vagus and auricular margin non-vagus by the obvious decrease (P< 0.01) in the comparison of the TCM symptoms scores in ATVNS (18.94±10.90) and ANVNS (19.89±12.19) after the 12week treatments [(13.83±11.82); (14.11±9.38), respectively].3.4 Safety IndexThe abnormal ratio of systolic pressure in ATVNS (123.66±14.34 mmHg) decreased after the 12w treatments (118.60±13.53 mmHg) (P<0.05). It showed no statistical significance(P>0.05) by comparing the difference in heart rate, breath frequency and body temperature in all groups before and after the 12w treatments. The safety-rate was rated as Level 2.4 Conclusions1) The treatment could reduce the blood glucose, HbAlc, BMI, systolic pressure, and improve the symptoms, and the 2hPG by stimulating the auricular vagus nerve.2) The treamtment could reduce the blood glucose, HbAlc and improve the symptoms by stimulating on the auricular non-vagus nerve.3) The treatment showed superior effect on reducing 2hPG comparing with the auricular non-vagus nerve. And effect on reducing blood glucose, BMI, HbAlc and improving symptoms through stimulating the auricular vagus nerve, comparing with the blank control.4) Blood glucose and HbAlc on BC elevated, ins subjects without any intervention after 12 weeks.5) Vagus nerve Elctrostimulation is a new and safety treatment of improving the metabolism of glucose and preventing DM of auricular vagus nerve stimulation.更多还原