Analysis on Traditional Chinese Medicine syndrome elements and relevant factors for senile diabetes

Online Submissions: http://www.journaltcm.com J Tradit Chin Med 203 August 5; 33(4): 473478 info@journaltcm.com ISSN 02552922 203 JTCM. All rights reserved. CLINICAL STUDY TOPIC Analysis on Traditional Chinese Medicine syndrome elements and relevant factors for senile diabetes Junping Wei, Rui Wu, Dandan Zhao aa Junping Wei, Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, eijing 00053, China Rui Wu, Department of Endocrinology, South Area of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, eijing 02600, China Dandan Zhao, Preclinical Medicine School, eijing University of Chinese Medicine, eijing 00029, China Supported by The Special Scientific Research Program of State Administration of Traditional Chinese Medicine: Methodological Evaluation of Treating Type 2 Diabetes with Syndrome Differentiation Methods ased on Three Stages In TCM (No. 0607LP42) Correspondence to: Prof. Junping Wei, Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, eijing 00053, China. weijunping@ 26.com Telephone: +860880028 Accepted: February 9, 203, Qi, blood stasis, and phlegm turbidity are most commonly seen among 4SE combinations. Yang is typically related to illness course and MI, phlegm turbidity to hypertension and hyperlipidemia, excessive heat to diabetic microangiopathy, and blood stasis to illness course and diabetic macroangiopathy. CONCLUSION: SD pathogenesis has a in origin and excess in superficiality. Deficiency syndrome mainly manifests as of both Qi and Yin, and concurrently in Yang. Excess syndrome is characterized by blood stasis and phlegm turbidity. SEs analysis provides a basis for the prevention and treatment of SD with TCM and lays the foundation for objectively evaluating multicentric clinical research for SD in TCM. 203 JTCM. All rights reserved. Abstract OJECTIVE: To explore the laws governing the distribution of Traditional Chinese Medicine (TCM) syndrome elements (SEs) of senile diabetes (SD) and their relationship to relevant factors. METHODS: An investigation of patients who met the inclusion criteria was conducted by trained doctors, using case report forms. All related data were collected, including body mass index, glycated hemoglobin, illness course, complications, symptoms, and tongue and pulse manifestation. The SEs of each patient were judged by three qualified associate chief physicians independently. RESULTS: The main SEs of SD are Yin, Qi, blood stasis, and phlegm turbidity. Yin Key words: Diabetes mellitus; Aged; Medicine, Chinese traditional; Syndrome complex INTRODUCTION Senile diabetes (SD), a common disease among senile people, refers to diabetes that occurs after patients are 60 years old or diabetes that extends to 60years old or older after its onset. As the average age increases in China, SD incidence is rising yearly. A 2002 survey showed that SD incidence was 5% among people over 60 in eijing. SD negatively influences quality of life, and its acute and chronic complications can cause premature disability or even death. Modern medicine can control blood glucose but has limited effects on improving SD symptoms and controlling its complications. Traditional Chinese Medicine (TCM) character JTCM www. journaltcm. com 473 August 5, 203 Volume 33 Issue 4

izes treatment by syndrome differentiation and plays an increasingly important role in the treatment of SD and its complications in China. 2 Syndrome elements (SEs) summarizing the cause, nature, focus, and situation of a disease at some stage reflect the innate character of the disease and act as the basis of its clinical treatment. Use and mastery of SEs in clinical practice are important to TCM. SEs explaining syndromes can not only solve the complexity and flexibility of TCM syndrome differentiation but also objectively reflect the law of SD pathogenesis, thus deeply studying the objectification and standardization of syndrome. 3 In this study, we analyzed clinical data obtained in an epidemiological survey of 296 SD patients, explored the laws of SEs of SD, and analyzed relevant factors. Therefore, we provide a valuable reference for the standardization of SD syndrome differentiation to effectively direct clinical practice. METHODS Inclusion criteria (a) Patients conformed to the standard for diagnosing diabetes in both Western Medicine and TCM. In Western Medicine, diabetic patients conformed to the "Standard for Diagnosing Diabetes and Other Types of Hyperglycemia" issued by WHO in 999. 4 The standard for diagnosing diabetes in TCM was from the teaching materials of Traditional Chinese Internal Medicine (6th edition). 5 (b) Patients were over 60 years old. (c) Patients signed an acknowledgement agreement. Exclusion criteria (a) Patients had serious primary diseases of heart, liver, kidney, and hematopoietic system, or psychiatric diseases. (b) Patients had acute complications of diabetes such as diabetes ketosis. Design of experiment The experiment was a clinical crosssectional survey. We used a custom form for observing TCM SEs of SD to collect clinical data on diabetics over 60 years old in Guang'anmen Hospital under China Academy of Chinese Medical Sciences from April 20 to June 202. This study conformed to the standards of medical ethics and was approved by the ethics committee of the hospital. All patients signed an acknowledgement agreement. Three trained chief physicians judged the SEs of 296 SD patients. TCM SEs were divided into types, in reference to syndromes in TCM terms of clinical diagnosis and treatment and Chinese standards for diagnosing and treating diabetes combining TCM and Western Medicine. The rules for judging SEs were used according to The Principle for Directing Clinical Research into New Chinese Drugs, TCM diagnostics, and teaching material of Traditional Chinese Internal Medicine (6th edition). 58 Nine groups of syndromes comprised 52 symptoms, tongue conditions, and pulse conditions. Qi manifests as tiredness, pale complexion, short breath, excessive sweating, spontaneous sweating, softened and weakened limbs, pale tongue with a thin coating, and a weak and thready pulse. Yin manifests as dysphoria with a hot sensation in the chest, palms and soles, night sweating, dry mouth, dry throat, blurred vision, insomnia, red tongue with less coating or no coating, and a fast and thready pulse. Yang manifests as aversion to cold, cold limbs, pale complexion, facial and body edema, loose stool, frequent night urination, urinary incontinence, a pale enlarged tongue with a white coating, and a deep or deepslow pulse. manifests as pale or yellow complexion, pale lips, dizziness, vertigo, palpitation, dreaminess, and a thready pulse. Phlegm turbidity manifests as a heavy sensation of body and limbs, abdominal distension, oppressed feelings in the chest, poor appetite, a sticky and greasy tongue with a whitegreasy or whitethick coating, and a slippery pulse. Excessive heat manifests as eating and large appetite, thirst and excessive drinking, vexation, insomnia, dry stool, yellow urine, a red tongue with yellow coating, and a rapid pulse. Dampheat manifests as a poor appetite, abdominal distension, a heavy sensation of body and limbs, thirst, bitter taste in mouth, a sticky and greasy tongue, sticky stool, dry or loose stool, yellow urine, a red tongue with a yellow greasy coating, and a slippery and rapid pulse or a rapid pulse. Cold dampness manifests as aversion to cold, a heavy sensation of head and body, joint pain, abdominal distension, loose stool, a pale tongue with a white coating, and a slippery pulse. stasis manifests as numbness of the limbs, difficulty in movement, dry and rough skin, general pain, chest pain, waist pain, knee pain, purple lips, petechiae and purpura on the tongue or its edge, a light or dark purple tongue with hypoglossal purple collaterals, a rough pulse, a deep and rough pulse, a thready and rough pulse, or a taut pulse. Clinical data Among the 296 SD patients were 36 males (45.9%) and 60 females (54.% ) aged 6087 years, (70 ± 7) years on average. Illness course was 40 years, with an average of (4±9) years. Statistic method SPSS 7.0 statistics software (SPSS Inc., Chicago, IL, USA) was used to build a database. xˉ ±s was used to express measurement data in normal or similarly normal distribution. Quartiles were used to express measurement data not in normal distributions. 0 or were used to express binary enumeration data and frequency was counted. Logistic regression analysis was used for factors influencing SEs. P<0.05 or P<0.0 was considered statistical difference. JTCM www. journaltcm. com 474 August 5, 203 Volume 33 Issue 4

RESULTS Distribution of SEs in SD patients Among the SEs of SD, Yin and Qi had the highest frequency, followed by blood stasis, phlegm turbidity, and less by cold dampness. Among SE combinations, the 4SE combination was the most common, 6SE combination was the least common, and no single SE was found. Among the 4SE combinations, the combination of Qi, Yin, phlegm turbidity, and blood stasis was most common. Among the 296 patients were 4 cases of syndrome (4.7%), 282 cases of excess complication (95.3%), and no cases of excess syndrome (0%). Order of SEs SEs related to Qi appeared in the following order: Yin (n=205) >blood stasis (n=59) > phlegm turbidity (n=00) >Yang (n=97) > blood (n=79) >excessive heat (n=68) > dampheat (n=62)>cold dampness (n=22). SEs related to Yin appeared in the following order: Qi (n=205) >blood stasis (n=69) > phlegm turbidity (n=6) >Yang (n=03) > blood (n=88) >excessive heat (n=80) > dampheat (n=7)>cold dampness (n=23). SEs related to Yang appeared in the following order: Yin (n=03) >Qi (n= 97) >blood stasis (n=87) >phlegm turbidity (n=55) > blood (n=34) >excessive heat (n=27) > dampheat (n=25)>cold dampness (n=3). SEs related to blood appeared in the following order: Yin (n=88)>qi (n=79)> blood stasis (n=72)>phlegm turbidity (n=44)>excessive heat (n=34) =Yang (n=34) >dampheat (n= 26)>cold dampness (n=6). SEs related to phlegm turbidity appeared in the following order: Yin (n=6) >Qi (n= 00) >blood stasis (n=85) >Yang (n=55) > blood (n=44) >excessive heat (n=3) > dampheat (n=29)>cold dampness (n=3). SEs related to excessive heat appeared in the following order: Yin (n=80) >Qi (n=68) > blood stasis (n=54) >blood (n=34) >phlegm turbidity (n=3) >Yang (n=27) >dampheat (n=23)>cold dampness (n=0). SEs related to dampheat appeared in the following order: Yin (n=7) >Qi (n=62) > blood stasis (n=53) >phlegm turbidity (n=29) >blood (n=26) >Yang (n=25) >excessive heat (n=23)>cold dampness (n=0). SEs related to cold dampness appeared in the following order: Yin (n=25) >Qi (n=24) > blood stasis (n=20) >phlegm turbidity and Yang (n=3) >blood (n=6) >excessive heat and dampheat (n=0). SEs related to blood stasis appeared in the following order: Yin (n=69) >Qi (n=59) > Yang (n=87) >phlegm turbidity (n=85) > blood (n=72) >excessive heat (n=54) > dampheat (n=53)>cold dampness (n=20). Order of two SEs Two SEs appeared in the following order: Qi and Yin (n=205) >Yin and blood stasis (n=69)>qi and blood stasis (n=59)> Yin and phlegm turbidity (n=6) >Qi and phlegm turbidity (n=00) >Yin and Yang (n=03). SEs related to Qi and Yin appeared in the following order: blood stasis (n=38) > phlegm turbidity (n=89) >Yang (n=79) > blood (n=70) >excessive heat (n=6) > dampheat (n=56)>cold dampness (n=2). SEs related to Yin and Yang appeared in the following order: Qi (n=79) > blood stasis (n=67) >phlegm turbidity (n=46) >blood (n=24) >excessive heat (n=2) >dampheat (n=9)>cold dampness (n=0). SEs related to phlegm turbidity and Yin appeared in the following order: Qi (n=89) > blood stasis (n=75)>yang (n=46)>blood (n=37) >excessive heat (n=30) >dampheat (n= 26)>cold dampness (n=2). SEs related to phlegm turbidity and Qi appeared in the following order: Yin (n=89) > Table Distribution of SEs of SD patients (n=296) Qi Yin Yang Phlegm turbidity Excessive heat Dampheat Cold dampness stasis n 238 27 3 80 40 92 28 27 205 % 80.4 9.6 44.3 27.0 47.3 3. 43.2 9. 69.3 Notes: SE: syndrome element; SD: senile diabetes. Table 2 Distribution of SE combinations of SD patients (n=296) 2 SEs 3 SEs 4 SEs 5 SEs 6 SEs n 3 88 68 22 5 % 4.4% 29.7% 56.8% 7.4%.7% Notes: SE: syndrome element; SD: senile diabetes. JTCM www. journaltcm. com 475 August 5, 203 Volume 33 Issue 4

blood stasis (n=66)>yang (n=37)>blood (n=34) >excessive heat (n=25) >dampheat (n= 20)>cold dampness (n=). SEs related to Yin and blood stasis appeared in the following order: Qi (n=38)>phlegm turbidity (n=75) >Yang (n=67) >blood (n=60) >dampheat (n=48) >excessive heat (n= 47)>cold dampness (n=9). SEs related to Qi and blood stasis appeared in the following order: Yin (n=38) >Yang (n=68) >phlegm turbidity (n=66) >blood (n=56) >dampheat (n=45) >excessive heat (n= 44)>cold dampness (n=8). Logistic regressive analysis of SE factors Seven SE factors are MI, hypertension, hyperlipidemia, diabetic macroangiopathy and microangiopathy, illness course, and glycated hemoglobin. These seven SE factors are unrelated to Qi, Yin, blood, dampheat, and cold dampness. Yang is positively correlated to illness course and MI (P<0.05), and phlegm turbidity to hypertension and hyperlipidemia (P<0.05). Excessive heat is negatively correlated to diabetic microangiopathy (P<0.05). stasis is positively correlated to illness course and diabetic macroangiopathy (P<0.05). The results are shown in Tables 58, respectively. DISCUSSION TCM syndromes manifest in the cause, focus, and nature of a disease and the relationship between evil Qi and vital energy. The occurrence and development of a syndrome is influenced by many factors. An SE, the smallest unit of a syndrome, has specific symptoms different from other SEs. All clinical syndromes consist of SEs. In this study, we have found that SD pathogenesis belongs to in origin and excess in superficiality, based on investigation of the SEs. Deficiency syndrome is characterized by of both Qi and Yin, and by Yang. Excess syndrome mainly manifests as blood stasis and phlegm turbidity. Relevant research has found that Yang is typically related to illness course and MI, phlegm turbidity to hypertension and hyperlipidemia, excessive heat to diabetic microangiopathy, and blood stasis to illness course and diabetic macroangiopathy. Deficiency of both Qi and Yin is the pathologic basis of SD The results of this study show that Yin and Qi are most common. The incidence of each exceeds 80% and the incidence of both reaches 69.4%. The seven factors in the logistic regressive analysis are unrelated to Qi and Yin. Therefore, of both Qi and Yin are the pathologic bases of Table 3 Combinations of two SEs Qi and Yin Yin and Yang Phlegm turbidity and Yin Phlegm turbidity and Qi Yin and blood stasis Qi and blood stasis Qi 79 89 38 Yin 89 38 Yang 79 46 37 67 68 70 24 37 34 60 56 Phlegm turbidity 89 46 75 66 Excessiv e heat 6 2 30 25 47 44 Dampheat 56 9 26 20 48 45 Cold dampness 2 0 2 9 8 stasis 38 67 75 66 Note: SE: syndrome element. Table 4 Distribution of main SEs in 296 patients Combination of SEs n Percentage (%) Qi +Yin +blood stasis+phlegm turbidity Qi +Yin +Yang +others Qi +Yin +blood stasis Qi +Yin +phlegm turbidity Yin +blood stasis+others Qi +Yin +blood stasis+ dampheat Others Note: SE: syndrome element. 70 52 39 32 30 7 56 23.6 7.6 3.2 0.8 0. 5.7 8.9 JTCM www. journaltcm. com 476 August 5, 203 Volume 33 Issue 4

Table 5 Analysis of factors of Yang Sig. Exp () Illness course 0.382 0.95 3.839 0.050.466 MI 0.328 0.52 4.634 0.03.388 2.48 0.73 9.083 0.003 0.7 Notes: MI: body mass index; : regression coefficient β value; : standard error; : degree of freedom; Sig.: significance; Exp (): odds ratio. Table 6 Analysis of factors of excessive heat Sig. Exp () Microangiopathy 0.898 0.335 7.97 0.007 0.407 0.044 0.298 0.022 0.882 Notes: : regression coefficient β value; : standard error; : degree of freedom; Sig.: significance; Exp (): odds ratio. Table 7 Analysis of factors of blood stasis 0.957 Sig. Exp () Disease course 0.436 0.20 4.726 0.030.546 macroangiopathy 0.72 0.343 4.435 0.035 2.057 0.833 0.537 2.406 0.2 Notes: : regression coefficient β value; : standard error; : degree of freedom; Sig.: significance; Exp (): odds ratio. Table 8 Analysis of factors of phlegm turbidity 0.435 Sig. Exp () Hyperlipidemia 0.78 0.342 4.405 0.036 2.05 Hypertension 0.593 0.327 3.29 0.048.809 0.54 0.24 Notes: : regression coefficient β value; S.E: standard error; : degree of freedom; Sig.: significance; Exp (): odds ratio. SD. Qi and Yin decrease by a half in people over 50. 9 positively correlated to MI. 4 Malnutrition of internal organs can aggravate Qi. Many studies consider Yin as the most important factor of diabetes. However, diabetes weakens the digestive ability and malnutrition aggravates of both Qi and Yin to form a malignant cycle. Therefore, Qi and Yin are considered as important SEs in the development of SD and as its inherent cause. This conclusion is identical to descriptions in other relevant studies. 0 Qian Jin Yi Fang Yang Lao Da Li said that "People over 50 years with declining Yang Qi easily forget things and are lazy in daily life". The result of this study shows that the majority of SD patients suffer from Yang, which is related to illness course and MI. Central obesity is an important SDinducing factor that reduces insulin secretion, decreases the number of insulin receptors in peripheral target tissue, and lowers their affinity to insulin. 2 Senile obesity manifests as central (abdominal) obesity with a much higher waisttohip ratio (WHR). 3 Over 60% of SD patients have MI 24.0. Additionally, most patients with Yang are overweight or obese. The Lin Zheng Zhi Nan Yi An said that "Yang is manifested in fat body and weak pulse." Yang is The relationship between illness course and Yang suggests that the extension of illness course gradually aggravates the Yang of SD patients, which is identical to the theory of threestage syndromedifferentiation. 5 Therefore, when SD patients are treated with replenishing Qi and nourishing Yin, balancing Yin and Yang should be emphasized. Phlegm turbidity and blood stasis are important SEs of SD Phlegm turbidity and blood stasis are not only pathological products but also pathogenic factors of SD and they are important in the development of SD. It is difficult to eliminate phlegm turbidity and blood stasis because they interact as both cause and effect. The results of this study indicate that phlegm turbidity and blood stasis are important SEs of SD excess syndrome. Xue Zheng Lun said that "The reason for thirst is that blood stasis inside the body makes Qi unable to lift water. Therefore, the removal of blood stasis can quench thirst". 6 stasis has been shown to influence blood rheology, microcirculation, free radicals, and blood biochemistry in diabetics. 7,8 Additionally, phlegm turbidity is one of the core mechanism of dia JTCM www. journaltcm. com 477 August 5, 203 Volume 33 Issue 4.535 0.25 0.857

betes. 9 Su Wen Qi ing Lun said that "Most obese people must have taken too much sweet and fat food. Internal heat generated by fat food and abdominal distention induced by sweet food make ascending Qi form diabetes". 9 Research indicates that diabetic macroangiopathy is related to blood stasis, and hypertension and hyperlipidemia are related to phlegm turbidity. In the future, it is necessary to further explore the effects of phlegm turbidity and blood stasis in the development of SD. Activating blood circulation and eliminating phlegm turbidity can enhance the curative effect of SD patients with more and less excess. Applying drugs for activating blood circulation to treat diabetic macroangiopathy, including pathological changes of the lower limb vessels and carotid artery should be emphasized. Phlegmremoving methods cannot only treat SD but also control hyperglycemia, hypertension, and hyperlipemia. Overall, the results of this study reflect the law of SD syndromes, deepens research into the standardization of SD syndromes, and lays the foundation for a new system of syndromedifferentiating methods. Research into the SEs of SD and into combinations of SEs will provide evidence for treatment of SD and plays a role in directing clinical treatment. However, too few cases and limited objective indexes make it necessary to set up a better system of syndrome differentiation. This is necessary to carry out multicentric research of large samples according to strict requirements of evidencebased medicine, study coordinated influences of objective indexes on syndromes to deepen the connotation of "treatment based on syndromedifferentiation", and enhance the curative effect of TCM on SD. REFERENCES Chi JM. Practical diabetology. 3rd ed. eijing: People's Medical Publishing House, 200: 663. 2 Lin L. contemporary diabetes mellitus Traditional Chinese Medicine. st ed. eijing: People's Medical Publishing House, 2008: 272273. 3 Guo L, Wang YY, Zhang Z. Explanation of concepts of syndromes. eijing Zhong Yi Yao Da Xue Xue ao 2003; 26(2): 5. 4 World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. Geneva: WHO Document Production Services, 999: 7. 5 Wang YY. Internal medicine of Traditional Chinese Medicine. 2nd ed. Shanghai: Shanghai Science and Technology Press, 997: 30. 6 State ureau of Technical Supervision. Terminology of clinical diagnosis and treatment of Traditional Chinese Medicine (syndromesection). eijing: Standards press of china, 997: 6. 7 Zheng XY. Guiding principles of clinical research on new drugs of Chinese Traditional Medicine (on trial) 3rd ed. eijing: Chinese medical science and technology press, 2002: 233237. 8 Zhu WF. Diagnositics of Chinese medicine. 6th ed. eijing: Chinese medicine press of China, 999: 388390. 9 Wang HT. Interpretion Huangdi Inner Canon. eijing: People's Medical Publishing House, 2005: 0. 0 Jiang ZS, Ni Q, Lin L, et al. Study of syndromedifferentiation of type 2 diabetes based on the structured clinical information collection system. Zhong Hua Zhong Yi Yao Za Zhi 2007; 22(6): 396399. Sun SM (Tang dynasty). Qian Jin Yi Fang. Shanxi: Shanxi Science and Technology Publishing House, 200: 806. 2 Røder ME, Schwartz RS, Prigeon RL, Kahn SE. Reduced pancreatic cell compensation to the insulin resistance of aging: impact on proinsulin and insulin levels. J Clin Endocrinol Metab 2000; 85 (6): 22752280. 3 Morley JE. The elderly type 2 diabetic patient: special considerations. Diabet Med 998; 5 (Supp4): S4S46. 4 Ye TS (Qing dynasty). Guideline and medical record of clinical practice. eijing: China Press of Traditional Chinese Medicine, 2008: 6. 5 Lin L. Diagnositic and treatment standard of diabetes with integrative medicine 200. eijing: Military Medical Science Press, 200; 02. 6 Tang RC (Qing dynasty). Statement of blood stasis syndrome. eijing: China Medical Science Press, 20: 69. 7 Li H, Huang MZ, Zheng JQ, et al. Analysis of relationship between syndrome differentiation and blood sugar, blood lipid and blood rheology of type 2 diabetes. Fu Jian Yi Yao Za Zhi 2004; 26(2): 8385. 8 Zhang CX, Zuo W, Wang SH. Characteristics of syndrome differentiation and treatment of senile diabetes. Shi Yong Zhong Yi Nei Ke Za Zhi 2006; 20(5): 483. 9 Xiong XJ, Wang J. Treatment of diabetes from the aspect of phlegm turbidity. Zhong Guo Zhong Yi Ji Chu Yi Xue Za Zhi 2005; 4(2): 923924. JTCM www. journaltcm. com 478 August 5, 203 Volume 33 Issue 4