基于数据挖掘的仝小林教授应用干姜黄芩黄连人参汤治疗T2DM用药规律研究

【作者】 金末淑；

【导师】 仝小林；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2012， 博士

【摘要】 研究目的：运用数据挖掘技术揭示干姜黄芩黄连人参汤的核心脉症、用量规律、证候要素以及症一药一方之间的相关性,试图从中发现全小林教授应用干姜黄芩黄连人参汤治疗2型糖尿病的用药规律,为临床遣方用药提供客观依据,对2型糖尿病的治疗具有指导性意义。研究对象：纳入研究对象为2009年7月-2011年9月就诊于中国中医科学院广安门医院仝小林教授门诊的2型糖尿病患者,所选病例治疗时采用的方剂为干姜黄芩黄连人参汤,即以干姜、黄芩、黄连、人参(或西洋参,或红参,或太子参等)四味药物为主或加减方剂。参照病例纳入标准,筛选出符合要求的病例368例(744诊次)。研究方法：1.数据规范化：对其中的症状、中药名、药物剂量进行数据规范处理使资料统一规范化。2.建立数据库：将368份(744诊次)病例资料采用双人双机录入Epidata3.1软件。数据库包括编号、姓名、性别、年龄、治疗时间、体质指数、西药情况、症状、舌脉、空腹血糖、餐后2小时血糖、糖化血红蛋白、血脂、胰岛功能、治疗用药、药物剂量等多个方面。数据库中不含有文字,将每个变量对应唯一的编码,并通过填充空缺值、纠正非法值、数据变换等措施进行严格的质量控制。3.数据分析：从性别、年龄、病程、症状、药物种类、药物剂量等多个方面进行分析。应用SPSS16.0软件编程,进行频数分析、典型相关分析、因子分析、聚类分析、Logistic回归分析；应用Clementinel2.0进行关联规则分析。应用SPSS16.0软件编程,运用配对t检验或非参Wilcoxon Signed Ranks检验对治疗前后的指标变化进行比较。研究结果：1.频次统计结果：干姜黄芩黄连人参汤的核心脉症为乏力、不寐、视物模糊、口干、夜尿2次及以上、大便干、多汗、苔白、舌底瘀、舌体细颤、脉沉。2.用药剂量分析结果：干姜平均剂量为8.21±4.95克,常用治疗剂量范围为9-15克；黄连平均剂量为20.84±11.86克,常用治疗剂量范围为l 5-30克；黄芩平均剂量为24.97±13.60克,常用治疗剂量范围为30-45克；西洋参平均剂量为5.87±2.86克,常用治疗剂量范围为6-9克；红参平均剂量为4.52±3.03克,常用治疗剂量范围为3-6克。3.相关性分析结果：主药剂量与空腹血糖水平的相关性：干姜剂量与空腹血糖间存在弱的正相关(r=0.117),且这种相关性很显著(P=0.010)；黄连剂量与空腹血糖间存在弱的正相关(r=0.216),且这种相关性很显著(P=0.000)；黄芩剂量与空腹血糖间存在弱的正相关(r=0.186),且这种相关性很显著(P=0.000)；西洋参剂量与空腹血糖间存在很弱的正相关(r=0.090),且这种相关性也不显著(P=0.093)。主药剂量与糖化血红蛋白水平的相关性：干姜剂量与糖化血红蛋白间存在很弱的正相关(r=0.027)且这种相关性也不显著(P=0.647)；黄连剂量与糖化血红蛋白间存在弱的正相关(r=0.121),且这种相关性显著(P=0.037)；黄芩剂量与糖化血红蛋白间存在弱的正相关(r=0.103),且这种相关性也不显著(P=0.080)；西洋参剂量与糖化血红蛋白间存在很弱的负相关(r-=-0.001),且这种相关性也不显著(P=0.988)4.聚类分析结果：主药剂量聚类分析的结果,诸类群中第1类群药量组(干姜10.96克、黄连27.09克、黄芩32.31克、西洋参7.12克)占有绝对多数,在498诊次中,共计379次,占76.10%,这类群对应的脉症以乏力、视物模糊、不寐、口干、多汗、头晕、大便干、夜尿2次及以上、舌质暗、苔白、舌底瘀、舌体细颤、脉沉为主。5.因子分析结果：病程≤12月的病性证素4个：气虚、火热、阴虚、血瘀；病位证素3个：胃、脾、肾；12月<病程≤60月的病性证素4个：气虚、阴虚、血虚、火热；病位证素4个：脾、肝、胃、肾；60月<病程≤120月的病性证素4个：气虚、阴虚、血瘀、阳虚；病位证素3个：脾、肾、肝；120月<病程≤180月的病性证素3个：阴虚、气虚、血瘀；病位证素4个：肾、肝、脾、冒。病程>180月的病性证素2个：气虚、阴虚；病位证素3个：脾、肾、肝。6.关联规则分析结果：处方与症状间关联结果提示干姜黄芩黄连人参汤与乏力、不寐、视物模糊、口干、多汗、头晕这些症状间存在较强的相关性,可说明干姜黄芩黄连人参汤的主要病机为脾虚胃热,或兼有阴虚。7.治疗前后结果比较：纯中药组：疗程2个月的空腹血糖治疗前后有显著性差异(P<0.05)；疗程3-6个月的餐后2h血糖治疗前后有显著性差异(P<0.01)；疗程3-6个月的糖化血红蛋白治疗前后有显著性差异(P<0.05)。中药+西药组：疗程1个月、疗程2个月和疗程3-6个月的空腹血糖治疗前后有显著性差异(P<0.01)；疗程1-2个月和疗程3-6个月的餐后2h血糖治疗前后有显著性差异(P<0.05)；疗程3-6个月的糖化血红蛋白治疗前后有显著性差异(P<0.01)。8. Logistic回归分析结果：主药剂量与疗效之间关系：黄连、红参和西洋参剂量与疗效成正相关关系。其中黄连系数显著(P=0.020),西洋参系数几乎显著(P=0.059),而红参系数不显著(P=0.208)。结论：1.干姜黄芩黄连人参汤的核心脉症为乏力、不寐、视物模糊、口干、夜尿2次及以上大便干、多汗、苔白、舌底瘀、舌体细颤、脉沉。2.干姜黄芩黄连人参汤的主要病机为脾虚胃热,或兼有阴虚。3.主药常用治疗剂量为：干姜9克、黄连30克、黄芩30克、西洋参6克或红参6克。4.干姜黄芩黄连人参汤具有显著降糖的效果,治疗前与治疗后的空腹血糖、餐后2h血糖、糖化血红蛋白水平具有显著下降。5.干姜黄芩黄连人参汤中黄连和西洋参剂量与疗效成正相关关系。更多还原

【Abstract】 Objective:By analyzing the clinical data to find the main pulse and symptoms indicated by Ganjiang Huangqin Huanglian Renshen Tang, rules of dosage and the correlation between symptoms and herbs and formula, and further summarize the rules of treating T2DM with this formula and provide evidence for clinical practice, which is considered as guidance for treating T2DM.Subjects:Patients treated by professor Tong Xiaolin in Guang An’men hospital with the modified formula mainly composed of Ganjiang Huangqin Huanglian Renshen (Xiyangshen, Hongs hen, orTaizishen). Referring to the admittance criterion, 368 patients including 744 visits were chosen for this study.Methods:1. Standardization of data:make standards for symptoms, Name of Chinese herbs, and dosage.2. Establish a database:data of 368 patients (744 visits) was put into the software Epidata3.1 by two operators in two different computers, and then exported to Microsoft Office Excel 2007. The data included name, gender, age, treatment duration, BMI, western medication, symptoms, pulse and tongue, fast blood glucose(FBG),2 hours postprandial blood glucose (2h-PBG), glycosylation hemoglobinAlc (HbAlc), blood lipid, islet function, formulas, and dosage. The data didn’t include any words, and each variable is coding uniquely. All the data has been checked by missing data imputation, correction of illegal data and data conversion.3. Analysis of data:the data for analysis included symptoms, gender, duration, symptoms, drugs and dosage. By utilizing SPSS16.0, the analysis includes frequency analysis, factor analysis, canonical correlation analysis, cluster analysis and Logistic analysis; to compare the clinical effect before and after treatment with paired t test or Wilcoxon Signed Ranks; analyze correlation with Clement inel2.0.Results:1. Results of summarizing the frequency:core symptoms and pulse indicated by Ganjiang Huanglian Renshen Tang include fatigue, insomnia, blurred vision, dry mouth, nocturia (more than twice), dry stool, sweating, white coating, ecchymosis in the tongue, slightly trembling of the tongue body and deep pulse. 2. Analysis of dosage:average dosage of Ganjiang was 8.21±4.95g (therapeutic dosage ranging from 9 to 15 g); average dosage of Huanglian was 20.84±11.86g (therapeutic dosage ranging from 15 to 30 g); average dosage of Huangqin was 24.97±13.60g (therapeutic dosage ranging from 30 to 45g), average dosage of Xiyangshen was 5.87±2.86g(therapeutic dosage ranging from 6 to 9 g); average dosage of Hongshen was 4.52±3.03 g(therapeutic dosage ranging from 3 to 9g).3. Analysis of correlation:Correlation between principal medicine and FBG:FBG was positively correlated with dosage of Ganjiang, Huanglian and Huangqin, as when FBG was hinger, the dosage of these herbs increased, however the positive correlation between Xiyangshen(Hongshen) is very slight with FBG. Correlation between principal medicine and glycosylation hemoglobinA1c (HbA1c): glycosylation hemoglobinA1c (HbA1c) was positively correlated with Huanglian and Huangiqn, as glycosylation hemoglobinA1c(HbA1c) was higher, both dosage of Huangqin and Huanglian would increase; while Xiyangshen (Hongshen) had a slightly negative correlation with glycosylation hemoglobinA1c(HbA1c); the dosage of Ganjiang is very slight positive correlation with glycosylation hemoglobinA1c(HbA1c).4. Result of cluster analysis:the result of cluster analysis for principal ingredient (Ganjiang, Huagnlian, Huangqin and Xiyangshen), the middle dosage group (Ganjiang 10.96g, Huagnlian 27.09g, Huangqin 32.31g, Xiyangshen 7.12g) occupied the majority of these including 379 visits among 489 (76.10%); the core symptoms and pulse included fatigue, insomnia, blurred vision, dry mouth, nocturia (more than twice), dry stool, sweating, white coating, ecchymosis in the tongue, slightly trembling of the tongue body and deep pulse.5. Analysis of the factors:there were 4 elements for character of disease with duration less than 12 months:qi deficiency, heat, yin deficiency and blood stasis; 3 elements for disease location:stomach, spleen and kidney; there were 4 elements for character of disease with duration between 12 months and 60 months:qi deficiency, xue deficiency, yin deficiency and heat; 4 elements for disease location:spleen, liver, stomach and kidney; there were 4 elements for character of disease with duration between 60 months and 120 months:qi deficiency,yin deficiency, blood stasis and yang deficiency; 3 elements for disease location: spleen, kidney and liver; there were 3 elements for character of disease with duration between 120 months and 180 months:yin deficiency, qi deficiency and blood stasis; 4 elements for disease location:kidney, liver, spleen and stomach. there were 2 elements for character of disease with duration more than 180 months: qi deficiency and yin deficiency; 3 elements for disease location:spleen, kidney and liver. 6. Analysis of correlation:correlation between formula and symptoms indicates that Ganjiang Huangqin Huanglian Renshen Tang had a close correlation with symptoms of fatigue, insomnia, blurred vision, dry mouth, sweating and dizziness. It also proved that the pathogenesis indicated by the formula is spleen deficiency and stomach heat,or combined with yin deficiency.7. Comparison of clinical effect before and after the treatment:in TCM group, for 2 months duration there was obvious difference in FBG (P<0.05); for duration of 3 to 6 months, there was obvious difference in both 2h-PBG and HbAlc(P<0.01, P<0.05). in TCM+WMS group, for duration of 1 month,2 months and 3 to 6 months, there was obvious difference in FBG (P<0.01); for duration of 1 to 2 month, and 3 to 6 months, there was obvious difference in 2h-PBG (P<0.05, P<0.01); for duration of 3 to 6 months, there was obvious difference in HbAlc(P<0.01).8. Result of Logistic regression analysis:relationship between dosage of principal ingredients and clinical effects:as the dosage of Huanglian, Xiyangshen increases, it was more effective.Conclusion:1. Core symptoms and pulse indicated by Ganjiang Huangqin Huanglian Renshen Tang include fat igue, insomnia, blurred vision, dry mouth, nocturia (more than twice), dry stool, sweating, white coating, ecchymosis in the tongue, slightly trembling of the tongue body and deep pulse.2. The pathogenesis indicated by the formula is spleen deficiency and stomach heat, or combined with yin deficiency.3. The commonly used dosage of each ingredient:Ganjiang 9g, Huanglian 30g, Huangqin30g, Xiyangshen6g or Hongshen 6g.4. Ganjiang Huangqin Huanglian Renshen Tang has a positive on effect on lowering Blood Glucose.5. In this formula the effect has positive correlation with dosage of Huanglian, and Xiyangshen.更多还原