【作者】 雷枭；

【导师】 亓鲁光；

【作者基本信息】 成都中医药大学 ， 中医内科学， 2013， 博士

【摘要】 目的研究分析成都地区DOP中医证候类型,揭示DOP病机特点和证候分布规律,提高中医辨证论治DOP的临床疗效。方法通过前瞻性的调查研究,参照1999年世界卫生组织(WHO)和美国糖尿病协会(ADA)专家委员会制定的糖尿病诊断标准、中华医学会骨质疏松和骨矿盐疾病分会2011年3月制定的骨质疏松诊断标准以及《中华人民共和国国家标准·中医临床诊疗术语证候部分》和糖尿病中医防治指南·糖尿病代谢性骨病部分有关证候判定标准,自制糖尿病性骨质疏松中医证型调查表,收集了267例DOP患者。对每一例患者进行人工辨证,将辨证结果归纳总结并行频数分析。把四诊资料首先进行系统变量聚类分析,与人工辨证结果相比较,决定六类证型最为合适,然后再行K均值聚类分析,并对每一类证型进行主成分分析。结果(1)一般资料分析：267例DOP患者的平均年龄是69.3岁,发病年龄以60～80岁为高峰,达到68.2%。男性明显少于女性,男女比为0.59：1,表明女性的发病率高于男性。DOP患者体重指数多在正常范围内(平均20.67),肥胖和低体重者较少。糖尿病病程多在10年左右,病程较长。糖尿病慢性并发症高达55.8%,其中患一种并发症的患者有57例(21.4%),糖尿病周围神经病变最多,达到41例(15.4%)。合并两种并发症者66例(24.7%),糖尿病肾病合并周围神经病变最多,达到26例(9.7%)。有三种并发症者11例(4.1%),有四种并发症者15例(5.6%)。合并骨折的患者有12.0%,60～89岁为DOP合并骨折的高峰期。267例DOP患者空腹血糖偏高,糖化血红蛋白偏高,血钙、血镁、血磷、甘油三酯、胆固醇、尿酸都在正常范围内波动。(2)四诊资料分析：腰膝酸软是出现频率最高的症状,达到了77.9%,其后依次是神疲乏力(70.0%)、腰背酸痛(58.4%)、薄白苔(49.4%)、头晕目眩(46.1%)、舌淡红(45.3%)、畏寒喜温(41.6%)。出现频率在20%-40%之间的症状有：夜尿频多、肢体麻木、渴不多饮、沉细脉、失眠多梦、少苔或无苔、目干涩、抽筋、舌淡黯或紫黯、发落或齿摇、腰背刺痛、舌红、视物不清、四肢刺痛、耳鸣或耳聋、舌下青筋暴露、下肢水肿、便秘、急躁易怒、食欲不振。出现频率在10%-20%的症状有：细弱脉、便溏、口干喜饮、胖嫩舌、细涩脉、弦滑脉、细数脉、心悸、腰背冷痛、胸闷、四肢冷痛、口苦、瘦小舌、盗汗、白腻苔、腰背胀痛、自汗。出现频率少于10%的稀有症状是：黄腻苔、浮脉。舌体不正常者有胖嫩舌(14.2%)和瘦小舌(11.6%)。在舌质方面,舌淡红最多(45.3%),其次是舌淡黯或紫黯(29.6%),舌红(27.0%)最少。舌苔方面,薄白苔(49.4%)最多,少苔或无苔(30.7%)其次,白腻苔(10.5%)和黄腻苔(8.6%)最少。脉象多以相兼脉出现,单一脉象仅有浮脉(4.5%),比重最低,沉细脉(36.0%)最多,其余依次为细弱脉(19.9%)、弦滑脉(13.5%)、细涩脉(13.9%)、细数脉(13.1%)。(3)人工辨证分析结果：267例DOP患者可分为十个证型,排名前六位(93.26%)的证型依次是：阴阳两虚-瘀血阻络证、肝肾阴虚-瘀血阻络证、阴阳两虚证、肝肾阴虚证、肾阳亏虚证、肾阳亏虚-瘀血阻络证。较少的四种证候(6.74%)是肝肾阴虚-痰瘀阻滞证、肝肾阴虚-痰湿阻滞证、痰热阻滞证、瘀血阻络证。(4)变量系统聚类分析结果：①瘀血阻络证症状：腰背刺痛、肢体麻木、四肢刺痛、舌淡黯或紫黯、舌下青筋暴露、细涩脉。②痰湿困脾、痰湿瘀滞证症状：腰背胀痛、口干喜饮、心悸、胸闷、口苦、便秘、舌红、黄腻苔、弦滑脉、白腻苔。③肝肾阴虚、肝阳上亢证症状：神疲乏力、腰背酸痛、渴不多饮、视物不清、耳鸣或耳聋、头晕目眩、急躁易怒、失眠多梦、目干涩、抽筋、盗汗、瘦小舌、少苔或无苔、浮脉、细数脉。④肾阳亏虚、脾气亏虚证症状：腰膝酸软、腰背冷痛、发落或齿摇、畏寒喜温、食欲不振、四肢冷痛、自汗、下肢水肿、夜尿频多、便溏、胖嫩舌、薄白苔、舌淡红、细弱脉、沉细脉。(5)K均值聚类分析和主成分分析结果①肝肾阴虚、肝阳上亢证主要症状：急躁易怒、头晕目眩、失眠多梦、腰膝酸软、腰背酸痛、耳鸣或耳聋、发落或齿摇、舌红、少苔或无苔。次要症状：神疲乏力、目干涩、抽筋、视物不清、细弱脉。②肝肾阴虚、肝阳上亢、瘀血阻络证主要症状：腰膝酸软、腰背酸痛、失眠多梦、头晕目眩、少苔或无苔、薄白苔。次要症状：神疲乏力、目干涩、肢体麻木、渴不多饮、舌淡红、沉细脉。③肝肾阴虚、肝阳上亢、痰湿瘀滞证主要症状：腰膝酸软、腰背酸痛、头晕目眩、急躁易怒、口苦、口干喜饮、肢体麻木、心悸、四肢刺痛、便秘、舌红、舌淡黯或紫黯、黄腻苔。次要症状：神疲乏力、胸闷、失眠多梦、食欲不振、弦滑脉。④肾阳亏虚证主要症状：腰背酸痛、畏寒喜温、下肢水肿、胖嫩舌、薄白苔、舌淡红。次要症状：神疲乏力、夜尿频多、发落或齿摇、头晕目眩、沉细脉。⑤肾阳亏虚、瘀血阻络证主要症状：腰背刺痛、肢体麻木、四肢刺痛、畏寒喜温、夜尿频多、薄白苔、舌淡黯或紫黯、舌下青筋暴露、细涩脉。次要症状：腰膝酸软、腰背酸痛、神疲乏力。⑥阴阳两虚、瘀血阻络证主要症状：畏寒喜温、急躁易怒、头晕目眩、夜尿频多、腰背刺痛、肢体麻木、神疲乏力、腰背酸痛、薄白苔、白腻苔、舌淡黯或紫黯、舌下青筋暴露次要症状：腰膝酸软、腰背冷痛、耳鸣或耳聋、失眠多梦、渴不多饮、便溏、细弱脉。结论(1)人工辨证与聚类分析、主成分分析相结合的方法研究糖尿病性骨质疏松中医证型分布规律是可行的,能更好地指导中医临床。人工辨证和统计学分析各有优劣,相互结合可取长补短,本研究结果两者总体基本一致,表明本研究具有一定的可信度,也为今后研究DOP的证候打下了良好的基础,有助于提高中医治疗本病的临床疗效。(2)肾虚是本病的基本病机。肝肾阴虚是本病的重要病机,肝失疏泄是其重要环节。阴阳两虚是本病后期最常见的病理类型。血瘀是DOP的病理产物和加重因素,贯穿于整个疾病的始终。痰湿瘀滞可出现于本病的各个阶段,常导致各种各样的症状出现,使DOP经久不愈,变证百出。更多还原

【Abstract】 Objective:This paper is to observe and analyze TCM syndrome types of Diabetic Osteoporosis (DOP) in Chengdu, and to reveal its pathogenesis and syndrome distribution, so as to improve the clinical effects based on syndrome differentiation.Methods:A questionnaire of TCM syndromes of DOP was designed based on the following diagnostic criteria. The criteria of diabetes was formulated by World Health Organization (WHO) and the American Diabetes Association (ADA) Expert Committee in1999, criteria of osteoporosis was set by branch of osteoporosis and bone mineral salt disease, Chinese medical association in March2011, and the criteria of TCM syndromes were referenced both from China’s national standards of TCM syndrome terminology and chapters of diabetes metabolic bone disease associated syndrome in diabetes prevention and control guidelines with traditional Chinese medicine. Altogether,267DOP patients were enrolled. TCM syndrome type was determined by the investigators case by case. Results of syndrome differentiation were collected to carry out the frequency analysis. Data collected by four TCM diagnostic methods were analyzed by system variable cluster analysis and then compared with the TCM syndrome differentiation. Six TCM syndrome types of DOP were chosen, followed by a K-Means cluster analysis and a principal component analysis.Results:(1) General data analysis:Average age of the enrolled patients was69.3years old, with the peak onset between60and80(68.2%). The number of male patients was significantly lower than that of female with the ratio between male to female0.59:1, indicating high incidence of women. The body mass index (BMI) for most patients was normal with the average of20.67. The average diabetes duration was about10years. Up to55.8%cases had chronic complications of diabetes with57cases(21.4%) suffering from one complication with the most common one being diabetic peripheral neuropathy (41cases,15.4%)66cases(24.7%) suffering from two kinds of complications with the most common one being diabetic nephropathy and peripheral neuropathy (26cases,9.7%),11cases (4.1%) suffering from three kinds of complications, and15cases (5.6%) suffering from four kinds of complications. There were12%patients complicated with bone fracture, among which, the peak onset was between60to89years old. All the patients had high fasting blood sugar and high glycated haemoglobin and their blood calcium, magnesium, phosphorus, triglycerides, cholesterol, and uric acid were all on normal range. (2) Data analysis collected by the four TCM diagnostic methods:Soreness and weakness of waist and knees was the most frequent symptom, accounting for77.9%, followed by fatigue (70.0%), backache (58.4%), thin white tongue coating (49.4%), dizziness (46.1%), normal tongue (45.3%), and aversion to cold and favor of warm (41.6%). Symptoms with frequency between20%and40%were:frequent night urination, numbness of the limbs, thirst without much drink, deep thready pulse, insomnia and dreaminess, scanty tongue coating, eye dryness, cramps, pale dark tongue or dark purple tongue, hair loss or teeth shaking, stabbing pain of the waist and back, red tongue, unclear vision, stabbing pain of the limbs, tinnitus or deafness, exposure of sublingual veins, edema of lower extremity, constipation, irritability, and loss of appetite. Symptoms with frequency between10%and20%were:thready weak pulse, loose stools, dry mouth and desire to drink, puffy and tender tongue, thready and choppy pulse, wiry and slippery pulse, rapid thready pulse, palpitations, cold pain of waist and back, chest tightness, cold pain of limbs, bitter taste, thin and small tongue, night sweating, white and greasy tongue coating, swelling pain of waist and back, and spontaneous perspiration. Symptoms with frequency less than10%were:yellow and greasy tongue coating and floating pulse.Abnormal tongue body includes puffy and tender tongue (14.2%) and thin and small tongue (11.6%). About tongue color, slight red was the most frequent (45.3%), followed by pale and dark or dark and purple (29.6%), and red tongue (27.0%). About tongue coating, thin and white tongue coating (49.4%) was the most common, followed by scanty or peeled coating (30.7%), white and greasy tongue coating (10.5%), and yellow and greasy tongue coating (8.6%). Complex Pulse was most common, with floating pulse (4.5%) as the only single pulse condition. Heavy deep thready pulse (36.0%) was the most common, followed by thready weak pulse (19.9%), wiry and slippery pulse (13.5%), thin and choppy pulse (13.9%), and rapid thready pulse (13.1%).(3) TCM syndrome differentiation:The267DOP cases can be divided into ten types with the top six syndrome types (93.26%) being:dual deficiency of Yin and Yang with blood stasis blocking collaterals syndrome, liver kidney Yin deficiency with blood stasis blocking collaterals, Yin and Yang deficiency syndrome, liver kidney Yin deficiency syndrome, kidney Yang deficiency and kidney Yang deficiency with blood stasis blocking collaterals syndrome. The four less-common syndromes (6.74%) were liver and kidney Yin deficiency with phlegm and blood stasis blockage, liver and kidney Yin deficiency with phlegm dampness blockage syndrome, phlegm heat blocking syndrome, and blood stasis blocking collaterals.(4) System variable cluster analysis:゜lood stasis blocking collateralsSymptoms:stabbing pain of waist and back, numbness and stabbing pain of the limbs, pale and dark tongue or purple and dark tongue, exposure of sublingual veins, and thready and choppy pulse.②Phlegm damp trapping spleen and phlegm-damp-blood stasis blockage syndromeSymptoms:swelling pain of waist and back, dry mouth with desire to drink, palpitations, chest tightness, bitter mouth, constipation, red tongue, yellow greasy tongue coating, or wiry and slippery pulse, and white greasy tongue coating.③Liver and kidney Yin deficiency with liver yang hyperactivity syndrome Symptoms:fatigue, backache, thirst without much drink, unclear vision, tinnitus or deafness, dizziness, irritability, insomnia and dreaminess, eye dryness, cramps, night sweats, thin and small tongue, scanty or peeled tongue coating, floating pulse, rapid thready pulse.④Kidney Yang deficiency with spleen qi deficiency syndromeSymptoms:Soreness and weakness of waist and knees, cold pain of waist and back, hair loss or teeth shaking, aversion to cold and favor of warmth, loss of appetite, cold pain of limbs, spontaneous perspiration, edema of lower extremity, frequent night urination, loose stools, puffy and tender tongue, thin and white tongue coating, slight red tongue, thready weak pulse, or deep thready pulse.(5) Results of K-means clustering analysis and principal component analysis㎜iver and kidney Yin deficiency withliver yang hyperactivity syndrome Main symptoms:irritability, dizziness, insomnia and dreaminess, Soreness and weakness of waist and knees, waist and back sore, tinnitus or deafness, hair loss or teeth shaking, red tongue, and scanty or peeled tongue coating. Secondary symptoms: mental fatigue and lacking of strength, eye dryness, cramps, unclear vision, and thready weak pulse.②Liver and kidney Yin deficiency with liver yang hyperactivity and blood stasis blocking collaterals syndrome Main symptoms:aching, or soreness and weakness of waist and knees, insomnia and dreaminess, dizzy, scanty or peeled tongue coating, thin and white tongue coating. Secondary symptoms: mental fatigue and lacking of strength, eye dryness, numbness of the limbs, thirst without much drink, slight red tongue, and deep thready pulse.③Liver and kidney Yin deficiency with liver yang hyperactivity and blockage of phlegm dampness and blood stasis syndrome Main symptoms: Aching, soreness and weakness of waist and knees, dizziness, irritability, bitter taste, dry mouth and desire to drink, numbness of the limbs, palpitations, limbs stabbing pain, constipation, red tongue, pale dark tongue or dark purple tongue, and yellow greasy tongue coating. Secondary symptoms:fatigue, chest tightness, insomnia and dreaminess, loss of appetite, and wiry slippery pulse.④Kidney Yang deficiency syndrome Main symptoms: waist and back soreness, aversion to cold and favor to warmth, edema of lower extremity, puffy and tender tongue, thin and white tongue coating, and red tongue. Secondary symptoms:fatigue, frequent night urination, hair loss or teeth shaking, dizziness, and deep thready pulse.⑤kidney Yang deficiency with blood stasis blocking collaterals syndrome Main symptoms:waist and back soreness, numbness and stabbing pain of the limbs, frequent night urination, thin and white tongue coating, pale dark or dark purple tongue, sublingual veins exposure, and thin choppy pulse. Secondary symptoms:Aching, or soreness and weakness of waist and knees, and fatigue.⑥dual deficiency of Yin and Yang with blood stasis blocking collaterals syndrome. Main symptoms:aversion to cold and favors to warmth, irritability, dizziness, frequent night urination, stabbing pain or soreness of the waist and back, numbness of the limbs, fatigue, thin and white tongue coating, white and greasy tongue coating, pale dark tongue or dark purple tongue, and sublingual veins exposure. Secondary symptoms:Soreness and weakness or cold pain of waist and back, tinnitus or deafness, insomnia and dreaminess, thirst without much drink, loose stool, and thready weak pulse.Conclusion: (1) It’s feasible to combine TCM syndrome differentiation, cluster analysis and principal component analysis for the study of TCM syndrome type distribution of DOP. It may serve as a better guidance for clinical practice of Traditional Chinese medicine. Both doctor-conducted TCM syndrome differentiation and statistical analysis have advantages and disadvantages and they can supplement each other. The two differentiation methods showed substantial consistency in this study, indicating the credibility of this study. This study may set a good foundation for further study of DOP syndrome types, and may be helpful to improve the clinical curative effects.(2) Kidney deficiency may be the basic pathogenesis of this disease. Liver and kidney Yin deficiency may be an important disease mechanism, and liver dysfunction may be an important part leading to the disease. Dual deficiency of Yin and Yang may be the most common syndrome types seen in the terminal stage of the disease. Blood stasis may be the pathological products and aggravating factors throughout the disease. Damp phlegm and blood stasis can be seen in every stage of the disease, often leading to all sorts of symptoms, long-lasting atrophic debility of bones, and lots of other complications.更多还原