- Email: [email protected]
The association between metabolic syndrome and body constitution in traditional Chinese medicine
European Journal of Integrative Medicine 14 (2017) 32–36
Contents lists available at ScienceDirect
European Journal of Integrative Medicine journal homepage: www.elsevier.com/locate/eujim
Research paper
The association between metabolic syndrome and body constitution in traditional Chinese medicine ⁎
Fei Xua,b,1, Yuanhao Zhanga,b,1, Wenqiang Cuic, Tao Yia,b, Zihui Tanga,b, , Jingcheng Donga,b,
MARK ⁎
a
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China, China The Institutes of Integrative Medicine of Fudan University, Shanghai, China, China c Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China, China b
A R T I C L E I N F O
A B S T R A C T
Keywords: Metabolic syndrome Traditional Chinese medicine Body constitution Yang-deficiency Chinese population
Introduction: Humans have individual characteristics, and the TCM constitution reflects their inherent nature. Little is known in the general population about the relationship between TCM constitutions and metabolic syndrome (MetS). The purpose of the present study was to investigate the associations between traditional Chinese medicine (TCM) body constitutions and MetS. Methods: This was a large-scale, community-based, cross-sectional study of 3748 participants. TCM constitution and the diagnosis of MetS were based on a body constitution questionnaire (BCQ) and a self-reported medical history, respectively. Univariate and multivariable logistic regressions (MLR) were applied to assess the strength of the associations. Results: Univariate analysis showed that Yang-deficiency was significantly associated with MetS (P < 0.01). Furthermore, multivariable linear regression showed that Yang-deficiency constitution was significantly and independently associated with MetS, after controlling for potential confounding factors (P < 0.01). As compared with neutral participants (ostensibly normal, with no imbalance), participants with Yang-deficiency constitutions had a higher prevalence of MetS. Conclusion: Our observations suggest that Yang-deficiency constitution is closely associated with MetS and provides evidence for the hypothesis that an unbalanced constitution is closely related to MetS in terms of occurrence, development, diagnosis, treatment, and prognosis.
1. Introduction Traditional Chinese medicine (TCM) has a complete system for classifying functional states. Constitutions (called tizhi), a widely used term in China, have been considered the standard in terms of health care, sub-health prevention, quality of life evaluation, and disease diagnosis, treatment and prevention [1]. Humans differ individually, and the TCM constitution reflects the nature and inherent characteristics of the human body, which are influenced by heredity, ontogeny and environment [2]. Constitution also determines an individual’s pathological tendencies, resistance and susceptibility to disease, as well as disease outcomes [3]. The most representative and accepted theory for classifying constitution in TCM in China was proposed by Wang et al. [4] and is measured with a body constitution questionnaire (BCQ) [5].
The Nine-Constitution Scale consists of Neutral, Qi-deficiency, Yangdeficiency, Yin-deficiency, Phlegm-dampness, Damp-heat, Stagnantblood, Stagnant-qi and Inherited-special constitutions. An unbalanced constitution is significantly associated with chronic disease. For instance, Yin- and Yang-deficiency constitutions are correlated with diabetes mellitus (DM) [6]; Yang-deficiency and Qi-deficiency constitutions mostly occur in elderly patients with insomnia [7]; and Yindeficiency constitution is related to some extent with disturbances in endocrine and immune functions [8]. Metabolic syndrome (MetS), a group of metabolic disorder conditions, is surrounded by a cluster of interconnected risk factors, including high blood pressure, central obesity, hyperglycaemia, hypertriglyceridemia and low high-density lipoprotein cholesterol level [9]. It contributes to about a fivefold increased risk of type 2 DM (T2DM)
Abbreviations: TCM, traditional Chinese medicine; MetS, metabolic syndrome; DM, diabetes mellitus; CAD, coronary artery disease; MLR, multivariable logistic regression; CRE, creatinine; LH, luteinizing hormone; TSH, thyroid stimulating hormone; CI, cerebral infarction ⁎ Corresponding authors at: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China E-mail addresses: [email protected] (F. Xu), [email protected] (Y. Zhang), [email protected] (W. Cui), [email protected] (T. Yi), [email protected] (Z. Tang), [email protected] (J. Dong). 1 These authors contributed equally to this work http://dx.doi.org/10.1016/j.eujim.2017.08.008 Received 26 February 2017; Received in revised form 21 August 2017; Accepted 22 August 2017 1876-3820/ © 2017 Published by Elsevier GmbH.
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
upon examination. Necessary corrections have been done.
and a twofold increased risk of coronary artery disease (CAD) [10]. Sadly, the mainstay of treatment for MetS is drug therapy for the risk factors, along with lifestyle and diet modifications; there is no definitive treatment for it. However, several studies have demonstrated that TCM, as a prominent alternative to modern medicine, is promising for treating MetS [11]. In TCM theory, human beings exhibit vulnerability to disease and receptivity to treatment based on their individual constitution. Previous studies have revealed that the TCM constitution demonstrates strong effects on pregnant women, T2DM, potential repair capacity and the health-related quality of life in T2DM patients [12–14]. One study has shown that Phlegm-dampness, Dampness-heat and Qi-deficiency constitutions were the three dominant constitutional types in senior retired military personnel of the People's Liberation Army [15]. However, this single-centre study involved elderly and military populations with special characteristics. Therefore, little is known about the relationship between TCM constitutions and MetS in the general population. We hypothesise that TCM constitution is associated with MetS. The purpose of this study was to evaluate the extent to which TCM constitution is associated with MetS in a Chinese sample.
2.3. Statistical analysis Differences in variables among subjects grouped by MetS were determined by one-way analysis of variance. Among groups, differences in properties were detected by χ2 analysis. Univariate regression analysis was performed to determine the TCM constitution variables associated with outcomes. Additionally, multivariable linear regression (MLR) was performed to control potential confounding factors and determine the independent contribution of variables to outcomes. Results were analysed using the Statistical Package for Social Sciences for Windows, version 16.0 (SPSS, Chicago, IL, USA). Tests were two-sided, and a P value of < 0.05 was considered significant. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated for the relative risk of body constitution of TCM and the outcome of MetS. 3. Results 3.1. Clinical characteristics of subjects
2. Methods
The clinical characteristics of the 3748 Chinese subjects agreeing to take part in the study are listed in Table 1. In the total sample, the mean age was 69.33 years, and the mean height and weight were 161.26 cm and 62.37 kg, respectively. The prevalence of HTN, CI, DM and overweight were 42.58%, 3.31%, 16.84% and 35.73%, respectively. The prevalence of MetS DM was 10.81% in this sample. There were significant differences in weight between the MetS and non-MetS groups (P < 0.001). Additionally, there was a significantly higher prevalence of HTN, obesity and DM between patients with MetS and without MetS groups, respectively (P < 0.001 for all).
2.1. Study population A previous analysis of TCM constitution and chronic disease has previously been conducted in a random sample of the Chinese population [16]. More than 4000 participants aged 30–90 years were recruited from rural and urban communities in Shanghai between 2011 and 2014. Written consent was obtained from all patients before the study, which was performed in accordance with the ethical standards in the Declaration of Helsinki, and was approved by the ethical committee of Huashan Hospital. Some participants with chronic diseases and conditions that could potentially affect the risk analysis were excluded. Briefly, the exclusion criteria were 1) severity renal and liver function abnormal and 2) pregnant women. In this study, a total of 4132 participants signed a consent form before taking part in the study. One hundred twelve participants were excluded as following exclusion criteria. Additionally, one hundred and eighty nine participants did not collect the complete data regarding constitution of TCM, and for eighty three participants there was incomplete information on outcomes. Finally, a total of 3748 participants were available for the data analysis.
3.2. Univariate and multiple variable analyses for MetS Univariate linear regression analyses were developed to include TCM constitution to estimate its association with MetS. The Yang-deficiency variable was significantly associated with MetS (P = 0.002, Table 2). The comparison of MetS prevalence among groups according to TCM constitution revealed that the prevalence of MetS was 11.49% and 7.76% in Neutral participants and Yang-deficient participants Table 1 Baseline characteristics of participants.
2.2. Data collection
Variable
Most of the participants affected by common diseases were registered and managed by community healthcare centers, and they were diagnosed according to clinical records. Briefly, DM was defined by oral glucose tolerance test (OGTT) and either HbAlc > 6.5% or the use of insulin or hypoglycemic medications. MetS was diagnosed according to the updated National Cholesterol Education Program/Adult Treatment Panel III criteria (WHO Western Pacific Region obesity criteria). In order to ascertain this information, all participants underwent a complete clinical baseline characteristics evaluation. The data collection method for demographic information, lifestyle, the medical history definitions of DM, body mass index (BMI), hypertension (HTN) and MetS have been detailed in a previous study [16]. In this study, according TCM diagnosis and evaluation criteria – such as tongue or pulse sign and syndrome, and standard a questionnaire for TCM body constitution, TCM constitution was assessed by three senior practitioners (senior TCM physicians). The definition of TCM constitution was based on BCQ (supplementary document 1) [5]. Neutral constitution refers to this type of person who does not have any unbalance or constitution complaints. They look healthy with normal skin color. They have proper appetite and sleep, and do not feel hot or cold easily. Their urine and stools are normal. The tongue is normal
MetS
Total
P value
405 69.6 ± 7.17 220(54.32%) 160.85 ± 8.41 70.91 ± 8.86 135.45 ± 14.77 70.52 ± 18.65 74.87 ± 10.88
3748 69.33 ± 7.53 2039(54.4%) 161.26 ± 15.19 62.37 ± 10.82 134.44 ± 19.98 67.12 ± 24.07 74.19 ± 13.73
– 0.441 0.972 0.56 < 0.001 0.801 0.470 0.289
2051(61.35%) 79(2.39%) 634(18.97%) 561(16.78%)
250(61.73%) 11(2.72%) 76(18.77%) 68(16.79%)
2301(61.39%) 90(2.42%) 710(18.94%) 629(16.78%)
0.883 0.843 0.923 0.996
Medical history HTN 1198(35.84%) DM 436(13.04%) CI 116(3.47%) Overweight 943(28.23%)
398(98.27%) 195(48.15%) 8(1.98%) 395(97.53%)
1596(42.58%) 631(16.84%) 124(3.31%) 1338(35.73%)
< 0.001 < 0.001 0.112 < 0.001
Demographic N Age Gender Height Weight SBP DBP HR Lifestyle Exercise Dietary Smoking Alcohol
non-MetS information 3343 69.29 ± 7.57 1819(54.41%) 161.31 ± 15.81 61.33 ± 10.58 134.17 ± 21.24 66.24 ± 25.29 74.1 ± 14.04
Note: SBP-systolic blood pressure, DBP-diastolic blood pressure, HR-heart rate, HTNhypertension, DM-diabetes mellitus, CAD-coronary artery disease, MetS-metabolic syndrome.
33
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
methods such as multiple variable regressions were employed to reduce the influence of confounding. To the best of our knowledge, this is the first study to perform an analysis of TCM constitutions and MetS in the general Chinese population, in order to explore which constitution is most closely associated with MetS in that population. Moreover, it is crucial for us to understand the predictive value and influence of TCM constitutions on MetS. Since not only one relevant factor affects the occurrence, progression and treatment of MetS, finding one vital factor would help clinicians and patients to treat and prevent it. Interestingly, in the present study of a large-scale sample of 3748 participants, there was a significant difference distribution of Yangdeficiency constitution between participants with and without MetS (P = 0.002, Table 2). After adjusting for potential confounding factors, the MLR showed that Yang-deficiency constitution was significantly and independently associated with MetS (P = 0.007, Table 3). What’s more, major risk factors, including HTN, DM, CAD, obesity, age and smoking, were found to contribute to the occurrence and progression of MetS. Constitution is an innate construct, partly genetically determined and partly acquired. A balanced constitution is ideal, which means yin and yang are in balance. Once unbalanced, disease or disharmony in the organs arises. From the perspective of TCM theory, Yang is mainly associated with functions and Yin with the organs. Persons with a Yangdeficiency constitution are characterized by reduced physical function and become easily fatigued [17]. The common symptoms of a body with Yang-deficient constitution would consist of cold limbs, inability to tolerate and vulnerability to diseases related to cold & dampness. Physical inactivity is highly associated with negative metabolic consequences such as increased abdominal fat and decreased insulin sensitivity [18], which are high risk factors for MetS. Moreover, according to TCM theory, Yang-deficiency mainly affects the functions of the kidney and spleen. In addition, Yang is active, and the Yang of the kidney and spleen plays a crucial role in the formation, distribution and metabolism of qi, blood and bodily fluid, which is a complex physiological process [14]. Thus, Yang-deficiency, associating with a low level of energy, leads to abnormal energy metabolism and water retention [19] and eventually to metabolic disorders such as DM, lipoid metabolism and high cholesterol, and finally to MetS [20]. Doing mild exercises, such as jogging and tai chi, would be of great benefit to patients with Yang-deficient constitution. Evidence from previous research has suggested a relationship between an unbalanced constitution and metabolic disturbances and related diseases, such as DM, insulin resistance, diabetic retinopathy, diabetic peripheral arterial disease and diabetic nephropathy [19,21]. In our study, unbalanced constitutions mostly occur in MetS, which is consistent with the above-published data. However, Liang et al. reported that Yin-deficiency constitution is associated with hypertension and diabetes [6]; Han et al. showed that Yin-deficiency, Phlegmdampness and Qi deficiency were the main constitution types in hypertension-complicated diabetes patients [22]. Inconsistent with our results, previous studies have shown that Yin-deficiency is the basis of DM [23]. As we all know, one disease has different pathological mechanisms and the mechanism of one disease might not be identical in different people [24]. The subjects in the above studies may have had different inherent characteristics, which are affected by environment, diet, region and other associated factors. Meanwhile, it should be pointed out that the above studies focused only on DM or hypertension or obesity, not directly on MetS. It is well known that TCM has a unique theoretical system, and TCM constitution represents the physical and physiological attributes of an individual. Few studies have confirmed that imbalanced constitutions have specific modern biological and medical mechanisms, which indicates that TCM theories can be explained well using modern biological knowledge. The causal relationships between MetS and inflammation have been extensively studied. Circulating levels of some inflammatory markers are elevated in MetS, such as inflammatory cells, C‐reactive protein (CRP), tumour necrosis factor-a (TNF-a), fibrinogen,
Table 2 Comparison of the prevalence of metabolic syndrome among groups according to their traditional Chinese medicine constitution. Variable
non-MetS
MetS
Total
P value
Neutral Qi_Deficient Yang_Deficient Yin_Deficient Phlegm_Dampness Damp_Heat Blood_Stasis Qi_Stagnation Special
1779 1029 832 297 270 113 64 50 72
231 124 70 33 32 11 10 3 13
2010 1153 902 330 302 124 74 53 85
0.527 0.002 0.427 0.647 0.372 0.593 0.186 0.285
Note: the difference analysis of distribution of body constitution of TCM between Mets and non-MetS groups by using χ2 test, respectively; MetS – metabolic syndrome, TCMtraditional Chinese medicine.
Fig. 1. Comparison of prevalence of metabolic syndrome among groups according to constitution of traditional Chinese medicine. The prevalence of metabolic syndrome was 11.49% and 7.76% in neutral participants.
Table 3 Multivariate analysis on constitution of traditional Chinese medicine for metabolic syndrome. Variable
Beta
S.E.
P value
OR
95.0% C.I
Yang_Deficient
−0.403
0.15
0.007
0.668
0.498–0.897
Note: Multivariate analysis adjusted for age, gender, exercise, dietary, smoking, alcohol.
(P = 0.002, Fig. 1), respectively. Univariate analysis demonstrated a negative correlation between TCM constitution and MetS. Multivariate logistic regression analyses were employed to evaluate the association between TCM constitution and MetS. After adjustment for relevant potential confounding factors, the MLR detected significant associations between Yang-deficiency constitution and MetS (P = 0.007, Table 3). In Yang-deficiency participants, the OR for MetS was 0.668. No significant associations were found with the other TCM constitutions (data not shown).
4. Discussion We conducted a large-scale, community-based, cross-sectional study to evaluate the relationship of TCM constitutions and MetS in a sample of the Chinese population. The characteristics of the participants and the prevalence of MetS may represent the Chinese population. In this study, we used a BCQ to combine the information about patients to estimate correlations. As this was a community sample study there were no inclusion and exclusion criteria. Although, we could not eliminate other confounder factors during the recruitment stage, data analysis 34
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
University. ClinicalTrials.gov Identifier: NCT02461472; and Shanghai Development Project of Shanghai Peak Disciplines-Integrative Medicine (20150407); and China Postdoctoral Science Foundation funded project (2017M611461).
platelet activator inhibitor 1 and interleukin‐6 (IL-6) [25]. Amazingly, in subjects with Yang-deficiency constitution, some inflammatory markers are active, like monocytes, TNF-a, IL-6, IL-8, IL-10 and IL-18 [17,26]. In other words, the relationship between Yang-deficiency constitution and MetS is possibly established by the presence of chronic inflammation. In addition, Yang-deficiency could also induce hormonal disorders, which is an important risk factor for MetS [17]. For instance, it was reported that creatinine (CRE), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) exert the greatest impact on Yangdeficiency (Yang-Xu) subjects [17]. Mounting evidence supports the role of hormones in mediating MetS [27]; for example, high normal TSH is a risk factor for metabolic syndrome [28]. We speculated that in Yang-deficiency subjects, hormonal disruption contributed to MetS. Furthermore, oxidative stress is relevant to MetS even though there is a controversy regarding its cause or consequences [29]. Evidence indicates that yin-yang balance represents antioxidation-oxidation balance, where yin represents antioxidation and yang represents oxidation [30]. The evidence shows that antioxidation-oxidation imbalance in Yang-deficiency patients is associated with MetS. We expect that further large-scale, case-controlled studies and investigations with western medicine and modern technologies will reveal the influence of Yangdeficiency constitution on MetS. Despite its contributions, this study has some limitations. Firstly, our study only paid attention to community-based data from Shanghai, so it may not represent China as a whole. A larger sample size and wider geographic representation are needed. Secondly, our study was performed on Han individuals, and people of other ethnicities were not included. Additionally, the self-reported methods used to assess common diseases may have led to a false-negative rate for MetS. Finally, the relationship between MetS and TCM constitutions was directly measured by a cross-sectional design and future follow-up studies will be required to verify the results. Our findings provide evidence that Yang-deficiency constitution is independently and significantly associated with MetS. A lower prevalence of MetS was found in participants with Yang-deficiency compared with participants with Neutral constitutions. These findings may provide insight for clinical practice with regard to prevention, diagnosis and treatment of MetS.
Competing interests None declared of conflict of interest. Author’s contributions F.X and Y.Z drafted the manuscript. W.C and Y.L participated in the design of the study and performed the statistical analysis. Z.T and J.D conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Authors’ information F.X, Y.Z, T.Y, Z.T, and J.D was Department of Integrative Medicine, Huashan Hospital, and Institutes of Integrative Medicine, Fudan University, Shanghai, China; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. Acknowledgments We thank the grant from Institutes of Integrative Medicine of Fudan University to support the study. References [1] Traditional Chinese medicine, Lancet 372 (2008) 1938–1940. [2] L. Heli, Z. Li, C. Zhiqiang, J. Huijuan, J. Lei, Physical and mental health conditions of young college students with different Traditional Chinese Medicine constitutions in Zhejiang Province of China, J. Tradit. Chin. Med. 35 (6) (2015) 703–708. [3] J. Wang, Y. Li, C. Ni, H. Zhang, L. Li, Q. Wang, Cognition research and constitutional classification in Chinese medicine, Am. J. Chin. Med. 39 (04) (2011) 651–660. [4] Q. Wang, Theories of Physical Constitutions of Traditional Chinese Medicine, Chinese Medical Science and Technology Publishing Company, Beijing, 1995. [5] CACM, Classification and identification of constitution theory of TCM (ZYYXH/ T157-2009), World J. Integr. Trad. West Med. 4 (2009) 303–304. [6] Y.C. Wong, M.C. Pang, Initial validation of the Yin-Yang assessment questionnaire for persons with diabetes mellitus, World J. Diabetes 11 (2015) 1198–1206. [7] C. Xia, Q.B. Zhu, F. Huang, J.H. Huang, H.D. Chen, M.J. Chen, W. Gu, B. Li, F.F. Fang, L.N. Wu, Traditional Chinese medicine constitution types in 127 elderly patients with insomnia: an investigation in communities of Yangpu District, Shanghai, Zhong Xi Yi Jie He Xue Bao 10 (8) (2012) 866–873. [8] Q. Wang, X.J. Ren, S.L. Yao, H.D. Wu, Clinical observation on the endocrinal and immune functions in subjects with yin-deficiency constitution, Chin. J. Integr. Med. 16 (1) (2010) 28–32. [9] K.G. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith Jr, International Diabetes Federation Task Force on Epidemiology, Prevention, Hational Heart, Lung, Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the study of obesity, Circulation 16 (2009) 1640–1645. [10] R.H. Eckel, K.G. Alberti, S.M. Grundy, P.Z. Zimmet, The metabolic syndrome, Lancet 9710 (2010) 181–183. [11] Y.P. Wang, E. Wat, C.M. Koon, C.W. Wong, D.W. Cheung, P.C. Leung, Q.S. Zhao, K.P. Fung, C.B. Lau, The beneficial potential of polyphenol-enriched fraction from Erigerontis Herba on metabolic syndrome, J. Ethnopharmacol. 187 (July (1)) (2016) 94–103. [12] C.-I. Tsai, Y.-C. Su, S.-Y. Lin, I.T. Lee, C.-H. Lee, T.-C. Li, Reduced health-related quality of life in body constitutions of Yin-Xu, and Yang-Xu, stasis in patients with type 2 diabetes: taichung diabetic body constitution study, Evid.-Based Complementary Altern. Med. 2014 (2014) 1–10. [13] S.-H. Kuo, H.-L. Wang, T.-C. Lee, T.-F. Chan, F.-H. Chou, L.-M. Chen, W.-T. Lin, Traditional Chinese medicine perspective on constitution transformations in perinatal women: a prospective longitudinal study, Women Birth 28 (2015) 106–111. [14] T. Yu, Z. Zhang, L. Xie, X. Ke, Y. Liu, The influence of traditional Chinese medicine
Declaration Ethical approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all patients before the study, and this study was approved by the Ethics Committee of Huashan Hospital, Shanghai, China (approval number 2009109). The methods were carried out in accordance with the approved guidelines. Consent for publication All authors read and approved the final manuscript. Availability of data and material The datasets generated and/or analysed during the current study are not publicly available due to private information but are available from the corresponding author on reasonable request. Dataset are from the study whose authors may be contacted at Center of Bioinformatics and Biostatistics, Institutes of Integrative Medicine, Fudan University. Funding Grants from the Institutes of Integrative Medicine of Fudan 35
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
[15]
[16]
[17]
[18] [19]
[20] [21]
[22]
patients, Zhongguo Zhong Xi Yi Jie He Za Zhi 33 (February (2)) (2013) 199–204. [23] J. Zhao, Y. Ding, Y. Wang, J. Li, Trinity of physique differentiation, diagnosis of disease and syndrome differentiation and clinical practice of diabetes, Zhonghua Zhong Yi Yao Za Zhi 24 (2009) 994–998. [24] W.Y. Jiang, Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science, Trends Pharmacol. Sci. 26 (2005) 558–563. [25] G. Kressel, B. Trunz, A. Bub, O. Hülsmann, M. Wolters, R. Lichtinghagen, D.O. Stichtenoth, A. Hahn, Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk, Atherosclerosis 202 (1) (2009) 263–271. [26] A. Tedgui, Z. Mallat, Cytokines in atherosclerosis: pathogenic and regulatory pathways, Physiol. Rev. 86 (2) (2006) 515–581. [27] S. Crunkhorn, Metabolic disorders. Hormone conjugate combats metabolic syndrome, Nat. Rev. Drug Discov. 15 (2016) 821. [28] B. Xu, H. Yang, Z. Wang, T. Yang, H. Guo, P. Cheng, W. He, M. Sun, H. Chen, Y. Duan, Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in a Chinese community-based population of euthyroid people aged 40 years and older, J. Biomed. Res. 30 (6) (2016) 476. [29] A. Carrier, Metabolic Syndrome and Oxidative Stress: A Complex Relationship, Antioxid. Redox Signal. 26 (9) (2017) 429–431. [30] B. Ou, D. Huang, M. Hampsch-Woodill, J.A. Flanagan, When east meets west: the relationship between yin-yang and antioxidation-oxidation, FASEB J. 17 (2) (2003) 127–129.
constitutions on the potential repair capacity after osteonecrosis of the femoral head, Complement. Ther. Med. 29 (2016) 89–93. Y-l Feng, G-y Zheng, C-q. Ling, The investigation of the correlation between metabolic syndrome and Chinese medicine constitution types in senior retired military personnel of the People’s Liberation Army, Chin. J. Integr. Med. 18 (2012) 485–489. J. Liu, F. Xu, N. Mohammadtursun, Y. Lv, Z. Tang, J. Dong, The analysis of constitutions of traditional Chinese medicine in relation to cerebral infarction in a Chinese sample, J. Altern. Complement. Med. (2017), http://dx.doi.org/10.1089/ acm.2017.0027 [Epub ahead of print]. H.J. Chen, Y.J. Lin, P.C. Wu, W.H. Hsu, W.C. Hu, T.N. Wu, F.P. Chen, Y.L. Lin, Study on Yang-Xu using body constitution questionnaire and blood variables in healthy volunteers, Evid. Based Complement Alternat. Med. 2016 (2016) 9437382. S. Golbidi, A. Mesdaghinia, I. Laher, Exercise in the metabolic syndrome, Oxid. Med. Cell Longev. 2012 (2012) 349710. S.H. Kuo, H.L. Wang, T.C. Lee, T.F. Chan, F.H. Chou, L.M. Chen, W.T. Lin, Traditional Chinese medicine perspective on constitution transformations in perinatal women: a prospective longitudinal study, Women Birth 28 (2015) 106–111. Y.M.Y. Jiang, Y. Yang, et al., Discussion on diabetes in terms of Yang deficiency, Med. World (2006) 114. K. Choi, J. Lee, J. Yoo, E. Lee, B. Koh, J. Lee, Sasang constitutional types can act as a risk factor for insulin resistance, Diabetes Res. Clin. Pract. 91 (March (3)) (2011) e57–e60. S.H. Han, K.Z. Li, J.M. Zheng, Z.X. Zheng, M.C. Lin, M.Y. Xu, Z.C. Yue, Study on the distribution of Chinese medical constitutions of hypertension complicated diabetes
36
Contents lists available at ScienceDirect
European Journal of Integrative Medicine journal homepage: www.elsevier.com/locate/eujim
Research paper
The association between metabolic syndrome and body constitution in traditional Chinese medicine ⁎
Fei Xua,b,1, Yuanhao Zhanga,b,1, Wenqiang Cuic, Tao Yia,b, Zihui Tanga,b, , Jingcheng Donga,b,
MARK ⁎
a
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China, China The Institutes of Integrative Medicine of Fudan University, Shanghai, China, China c Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China, China b
A R T I C L E I N F O
A B S T R A C T
Keywords: Metabolic syndrome Traditional Chinese medicine Body constitution Yang-deficiency Chinese population
Introduction: Humans have individual characteristics, and the TCM constitution reflects their inherent nature. Little is known in the general population about the relationship between TCM constitutions and metabolic syndrome (MetS). The purpose of the present study was to investigate the associations between traditional Chinese medicine (TCM) body constitutions and MetS. Methods: This was a large-scale, community-based, cross-sectional study of 3748 participants. TCM constitution and the diagnosis of MetS were based on a body constitution questionnaire (BCQ) and a self-reported medical history, respectively. Univariate and multivariable logistic regressions (MLR) were applied to assess the strength of the associations. Results: Univariate analysis showed that Yang-deficiency was significantly associated with MetS (P < 0.01). Furthermore, multivariable linear regression showed that Yang-deficiency constitution was significantly and independently associated with MetS, after controlling for potential confounding factors (P < 0.01). As compared with neutral participants (ostensibly normal, with no imbalance), participants with Yang-deficiency constitutions had a higher prevalence of MetS. Conclusion: Our observations suggest that Yang-deficiency constitution is closely associated with MetS and provides evidence for the hypothesis that an unbalanced constitution is closely related to MetS in terms of occurrence, development, diagnosis, treatment, and prognosis.
1. Introduction Traditional Chinese medicine (TCM) has a complete system for classifying functional states. Constitutions (called tizhi), a widely used term in China, have been considered the standard in terms of health care, sub-health prevention, quality of life evaluation, and disease diagnosis, treatment and prevention [1]. Humans differ individually, and the TCM constitution reflects the nature and inherent characteristics of the human body, which are influenced by heredity, ontogeny and environment [2]. Constitution also determines an individual’s pathological tendencies, resistance and susceptibility to disease, as well as disease outcomes [3]. The most representative and accepted theory for classifying constitution in TCM in China was proposed by Wang et al. [4] and is measured with a body constitution questionnaire (BCQ) [5].
The Nine-Constitution Scale consists of Neutral, Qi-deficiency, Yangdeficiency, Yin-deficiency, Phlegm-dampness, Damp-heat, Stagnantblood, Stagnant-qi and Inherited-special constitutions. An unbalanced constitution is significantly associated with chronic disease. For instance, Yin- and Yang-deficiency constitutions are correlated with diabetes mellitus (DM) [6]; Yang-deficiency and Qi-deficiency constitutions mostly occur in elderly patients with insomnia [7]; and Yindeficiency constitution is related to some extent with disturbances in endocrine and immune functions [8]. Metabolic syndrome (MetS), a group of metabolic disorder conditions, is surrounded by a cluster of interconnected risk factors, including high blood pressure, central obesity, hyperglycaemia, hypertriglyceridemia and low high-density lipoprotein cholesterol level [9]. It contributes to about a fivefold increased risk of type 2 DM (T2DM)
Abbreviations: TCM, traditional Chinese medicine; MetS, metabolic syndrome; DM, diabetes mellitus; CAD, coronary artery disease; MLR, multivariable logistic regression; CRE, creatinine; LH, luteinizing hormone; TSH, thyroid stimulating hormone; CI, cerebral infarction ⁎ Corresponding authors at: Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China E-mail addresses: [email protected] (F. Xu), [email protected] (Y. Zhang), [email protected] (W. Cui), [email protected] (T. Yi), [email protected] (Z. Tang), [email protected] (J. Dong). 1 These authors contributed equally to this work http://dx.doi.org/10.1016/j.eujim.2017.08.008 Received 26 February 2017; Received in revised form 21 August 2017; Accepted 22 August 2017 1876-3820/ © 2017 Published by Elsevier GmbH.
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
upon examination. Necessary corrections have been done.
and a twofold increased risk of coronary artery disease (CAD) [10]. Sadly, the mainstay of treatment for MetS is drug therapy for the risk factors, along with lifestyle and diet modifications; there is no definitive treatment for it. However, several studies have demonstrated that TCM, as a prominent alternative to modern medicine, is promising for treating MetS [11]. In TCM theory, human beings exhibit vulnerability to disease and receptivity to treatment based on their individual constitution. Previous studies have revealed that the TCM constitution demonstrates strong effects on pregnant women, T2DM, potential repair capacity and the health-related quality of life in T2DM patients [12–14]. One study has shown that Phlegm-dampness, Dampness-heat and Qi-deficiency constitutions were the three dominant constitutional types in senior retired military personnel of the People's Liberation Army [15]. However, this single-centre study involved elderly and military populations with special characteristics. Therefore, little is known about the relationship between TCM constitutions and MetS in the general population. We hypothesise that TCM constitution is associated with MetS. The purpose of this study was to evaluate the extent to which TCM constitution is associated with MetS in a Chinese sample.
2.3. Statistical analysis Differences in variables among subjects grouped by MetS were determined by one-way analysis of variance. Among groups, differences in properties were detected by χ2 analysis. Univariate regression analysis was performed to determine the TCM constitution variables associated with outcomes. Additionally, multivariable linear regression (MLR) was performed to control potential confounding factors and determine the independent contribution of variables to outcomes. Results were analysed using the Statistical Package for Social Sciences for Windows, version 16.0 (SPSS, Chicago, IL, USA). Tests were two-sided, and a P value of < 0.05 was considered significant. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated for the relative risk of body constitution of TCM and the outcome of MetS. 3. Results 3.1. Clinical characteristics of subjects
2. Methods
The clinical characteristics of the 3748 Chinese subjects agreeing to take part in the study are listed in Table 1. In the total sample, the mean age was 69.33 years, and the mean height and weight were 161.26 cm and 62.37 kg, respectively. The prevalence of HTN, CI, DM and overweight were 42.58%, 3.31%, 16.84% and 35.73%, respectively. The prevalence of MetS DM was 10.81% in this sample. There were significant differences in weight between the MetS and non-MetS groups (P < 0.001). Additionally, there was a significantly higher prevalence of HTN, obesity and DM between patients with MetS and without MetS groups, respectively (P < 0.001 for all).
2.1. Study population A previous analysis of TCM constitution and chronic disease has previously been conducted in a random sample of the Chinese population [16]. More than 4000 participants aged 30–90 years were recruited from rural and urban communities in Shanghai between 2011 and 2014. Written consent was obtained from all patients before the study, which was performed in accordance with the ethical standards in the Declaration of Helsinki, and was approved by the ethical committee of Huashan Hospital. Some participants with chronic diseases and conditions that could potentially affect the risk analysis were excluded. Briefly, the exclusion criteria were 1) severity renal and liver function abnormal and 2) pregnant women. In this study, a total of 4132 participants signed a consent form before taking part in the study. One hundred twelve participants were excluded as following exclusion criteria. Additionally, one hundred and eighty nine participants did not collect the complete data regarding constitution of TCM, and for eighty three participants there was incomplete information on outcomes. Finally, a total of 3748 participants were available for the data analysis.
3.2. Univariate and multiple variable analyses for MetS Univariate linear regression analyses were developed to include TCM constitution to estimate its association with MetS. The Yang-deficiency variable was significantly associated with MetS (P = 0.002, Table 2). The comparison of MetS prevalence among groups according to TCM constitution revealed that the prevalence of MetS was 11.49% and 7.76% in Neutral participants and Yang-deficient participants Table 1 Baseline characteristics of participants.
2.2. Data collection
Variable
Most of the participants affected by common diseases were registered and managed by community healthcare centers, and they were diagnosed according to clinical records. Briefly, DM was defined by oral glucose tolerance test (OGTT) and either HbAlc > 6.5% or the use of insulin or hypoglycemic medications. MetS was diagnosed according to the updated National Cholesterol Education Program/Adult Treatment Panel III criteria (WHO Western Pacific Region obesity criteria). In order to ascertain this information, all participants underwent a complete clinical baseline characteristics evaluation. The data collection method for demographic information, lifestyle, the medical history definitions of DM, body mass index (BMI), hypertension (HTN) and MetS have been detailed in a previous study [16]. In this study, according TCM diagnosis and evaluation criteria – such as tongue or pulse sign and syndrome, and standard a questionnaire for TCM body constitution, TCM constitution was assessed by three senior practitioners (senior TCM physicians). The definition of TCM constitution was based on BCQ (supplementary document 1) [5]. Neutral constitution refers to this type of person who does not have any unbalance or constitution complaints. They look healthy with normal skin color. They have proper appetite and sleep, and do not feel hot or cold easily. Their urine and stools are normal. The tongue is normal
MetS
Total
P value
405 69.6 ± 7.17 220(54.32%) 160.85 ± 8.41 70.91 ± 8.86 135.45 ± 14.77 70.52 ± 18.65 74.87 ± 10.88
3748 69.33 ± 7.53 2039(54.4%) 161.26 ± 15.19 62.37 ± 10.82 134.44 ± 19.98 67.12 ± 24.07 74.19 ± 13.73
– 0.441 0.972 0.56 < 0.001 0.801 0.470 0.289
2051(61.35%) 79(2.39%) 634(18.97%) 561(16.78%)
250(61.73%) 11(2.72%) 76(18.77%) 68(16.79%)
2301(61.39%) 90(2.42%) 710(18.94%) 629(16.78%)
0.883 0.843 0.923 0.996
Medical history HTN 1198(35.84%) DM 436(13.04%) CI 116(3.47%) Overweight 943(28.23%)
398(98.27%) 195(48.15%) 8(1.98%) 395(97.53%)
1596(42.58%) 631(16.84%) 124(3.31%) 1338(35.73%)
< 0.001 < 0.001 0.112 < 0.001
Demographic N Age Gender Height Weight SBP DBP HR Lifestyle Exercise Dietary Smoking Alcohol
non-MetS information 3343 69.29 ± 7.57 1819(54.41%) 161.31 ± 15.81 61.33 ± 10.58 134.17 ± 21.24 66.24 ± 25.29 74.1 ± 14.04
Note: SBP-systolic blood pressure, DBP-diastolic blood pressure, HR-heart rate, HTNhypertension, DM-diabetes mellitus, CAD-coronary artery disease, MetS-metabolic syndrome.
33
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
methods such as multiple variable regressions were employed to reduce the influence of confounding. To the best of our knowledge, this is the first study to perform an analysis of TCM constitutions and MetS in the general Chinese population, in order to explore which constitution is most closely associated with MetS in that population. Moreover, it is crucial for us to understand the predictive value and influence of TCM constitutions on MetS. Since not only one relevant factor affects the occurrence, progression and treatment of MetS, finding one vital factor would help clinicians and patients to treat and prevent it. Interestingly, in the present study of a large-scale sample of 3748 participants, there was a significant difference distribution of Yangdeficiency constitution between participants with and without MetS (P = 0.002, Table 2). After adjusting for potential confounding factors, the MLR showed that Yang-deficiency constitution was significantly and independently associated with MetS (P = 0.007, Table 3). What’s more, major risk factors, including HTN, DM, CAD, obesity, age and smoking, were found to contribute to the occurrence and progression of MetS. Constitution is an innate construct, partly genetically determined and partly acquired. A balanced constitution is ideal, which means yin and yang are in balance. Once unbalanced, disease or disharmony in the organs arises. From the perspective of TCM theory, Yang is mainly associated with functions and Yin with the organs. Persons with a Yangdeficiency constitution are characterized by reduced physical function and become easily fatigued [17]. The common symptoms of a body with Yang-deficient constitution would consist of cold limbs, inability to tolerate and vulnerability to diseases related to cold & dampness. Physical inactivity is highly associated with negative metabolic consequences such as increased abdominal fat and decreased insulin sensitivity [18], which are high risk factors for MetS. Moreover, according to TCM theory, Yang-deficiency mainly affects the functions of the kidney and spleen. In addition, Yang is active, and the Yang of the kidney and spleen plays a crucial role in the formation, distribution and metabolism of qi, blood and bodily fluid, which is a complex physiological process [14]. Thus, Yang-deficiency, associating with a low level of energy, leads to abnormal energy metabolism and water retention [19] and eventually to metabolic disorders such as DM, lipoid metabolism and high cholesterol, and finally to MetS [20]. Doing mild exercises, such as jogging and tai chi, would be of great benefit to patients with Yang-deficient constitution. Evidence from previous research has suggested a relationship between an unbalanced constitution and metabolic disturbances and related diseases, such as DM, insulin resistance, diabetic retinopathy, diabetic peripheral arterial disease and diabetic nephropathy [19,21]. In our study, unbalanced constitutions mostly occur in MetS, which is consistent with the above-published data. However, Liang et al. reported that Yin-deficiency constitution is associated with hypertension and diabetes [6]; Han et al. showed that Yin-deficiency, Phlegmdampness and Qi deficiency were the main constitution types in hypertension-complicated diabetes patients [22]. Inconsistent with our results, previous studies have shown that Yin-deficiency is the basis of DM [23]. As we all know, one disease has different pathological mechanisms and the mechanism of one disease might not be identical in different people [24]. The subjects in the above studies may have had different inherent characteristics, which are affected by environment, diet, region and other associated factors. Meanwhile, it should be pointed out that the above studies focused only on DM or hypertension or obesity, not directly on MetS. It is well known that TCM has a unique theoretical system, and TCM constitution represents the physical and physiological attributes of an individual. Few studies have confirmed that imbalanced constitutions have specific modern biological and medical mechanisms, which indicates that TCM theories can be explained well using modern biological knowledge. The causal relationships between MetS and inflammation have been extensively studied. Circulating levels of some inflammatory markers are elevated in MetS, such as inflammatory cells, C‐reactive protein (CRP), tumour necrosis factor-a (TNF-a), fibrinogen,
Table 2 Comparison of the prevalence of metabolic syndrome among groups according to their traditional Chinese medicine constitution. Variable
non-MetS
MetS
Total
P value
Neutral Qi_Deficient Yang_Deficient Yin_Deficient Phlegm_Dampness Damp_Heat Blood_Stasis Qi_Stagnation Special
1779 1029 832 297 270 113 64 50 72
231 124 70 33 32 11 10 3 13
2010 1153 902 330 302 124 74 53 85
0.527 0.002 0.427 0.647 0.372 0.593 0.186 0.285
Note: the difference analysis of distribution of body constitution of TCM between Mets and non-MetS groups by using χ2 test, respectively; MetS – metabolic syndrome, TCMtraditional Chinese medicine.
Fig. 1. Comparison of prevalence of metabolic syndrome among groups according to constitution of traditional Chinese medicine. The prevalence of metabolic syndrome was 11.49% and 7.76% in neutral participants.
Table 3 Multivariate analysis on constitution of traditional Chinese medicine for metabolic syndrome. Variable
Beta
S.E.
P value
OR
95.0% C.I
Yang_Deficient
−0.403
0.15
0.007
0.668
0.498–0.897
Note: Multivariate analysis adjusted for age, gender, exercise, dietary, smoking, alcohol.
(P = 0.002, Fig. 1), respectively. Univariate analysis demonstrated a negative correlation between TCM constitution and MetS. Multivariate logistic regression analyses were employed to evaluate the association between TCM constitution and MetS. After adjustment for relevant potential confounding factors, the MLR detected significant associations between Yang-deficiency constitution and MetS (P = 0.007, Table 3). In Yang-deficiency participants, the OR for MetS was 0.668. No significant associations were found with the other TCM constitutions (data not shown).
4. Discussion We conducted a large-scale, community-based, cross-sectional study to evaluate the relationship of TCM constitutions and MetS in a sample of the Chinese population. The characteristics of the participants and the prevalence of MetS may represent the Chinese population. In this study, we used a BCQ to combine the information about patients to estimate correlations. As this was a community sample study there were no inclusion and exclusion criteria. Although, we could not eliminate other confounder factors during the recruitment stage, data analysis 34
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
University. ClinicalTrials.gov Identifier: NCT02461472; and Shanghai Development Project of Shanghai Peak Disciplines-Integrative Medicine (20150407); and China Postdoctoral Science Foundation funded project (2017M611461).
platelet activator inhibitor 1 and interleukin‐6 (IL-6) [25]. Amazingly, in subjects with Yang-deficiency constitution, some inflammatory markers are active, like monocytes, TNF-a, IL-6, IL-8, IL-10 and IL-18 [17,26]. In other words, the relationship between Yang-deficiency constitution and MetS is possibly established by the presence of chronic inflammation. In addition, Yang-deficiency could also induce hormonal disorders, which is an important risk factor for MetS [17]. For instance, it was reported that creatinine (CRE), luteinizing hormone (LH) and thyroid stimulating hormone (TSH) exert the greatest impact on Yangdeficiency (Yang-Xu) subjects [17]. Mounting evidence supports the role of hormones in mediating MetS [27]; for example, high normal TSH is a risk factor for metabolic syndrome [28]. We speculated that in Yang-deficiency subjects, hormonal disruption contributed to MetS. Furthermore, oxidative stress is relevant to MetS even though there is a controversy regarding its cause or consequences [29]. Evidence indicates that yin-yang balance represents antioxidation-oxidation balance, where yin represents antioxidation and yang represents oxidation [30]. The evidence shows that antioxidation-oxidation imbalance in Yang-deficiency patients is associated with MetS. We expect that further large-scale, case-controlled studies and investigations with western medicine and modern technologies will reveal the influence of Yangdeficiency constitution on MetS. Despite its contributions, this study has some limitations. Firstly, our study only paid attention to community-based data from Shanghai, so it may not represent China as a whole. A larger sample size and wider geographic representation are needed. Secondly, our study was performed on Han individuals, and people of other ethnicities were not included. Additionally, the self-reported methods used to assess common diseases may have led to a false-negative rate for MetS. Finally, the relationship between MetS and TCM constitutions was directly measured by a cross-sectional design and future follow-up studies will be required to verify the results. Our findings provide evidence that Yang-deficiency constitution is independently and significantly associated with MetS. A lower prevalence of MetS was found in participants with Yang-deficiency compared with participants with Neutral constitutions. These findings may provide insight for clinical practice with regard to prevention, diagnosis and treatment of MetS.
Competing interests None declared of conflict of interest. Author’s contributions F.X and Y.Z drafted the manuscript. W.C and Y.L participated in the design of the study and performed the statistical analysis. Z.T and J.D conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Authors’ information F.X, Y.Z, T.Y, Z.T, and J.D was Department of Integrative Medicine, Huashan Hospital, and Institutes of Integrative Medicine, Fudan University, Shanghai, China; Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. Acknowledgments We thank the grant from Institutes of Integrative Medicine of Fudan University to support the study. References [1] Traditional Chinese medicine, Lancet 372 (2008) 1938–1940. [2] L. Heli, Z. Li, C. Zhiqiang, J. Huijuan, J. Lei, Physical and mental health conditions of young college students with different Traditional Chinese Medicine constitutions in Zhejiang Province of China, J. Tradit. Chin. Med. 35 (6) (2015) 703–708. [3] J. Wang, Y. Li, C. Ni, H. Zhang, L. Li, Q. Wang, Cognition research and constitutional classification in Chinese medicine, Am. J. Chin. Med. 39 (04) (2011) 651–660. [4] Q. Wang, Theories of Physical Constitutions of Traditional Chinese Medicine, Chinese Medical Science and Technology Publishing Company, Beijing, 1995. [5] CACM, Classification and identification of constitution theory of TCM (ZYYXH/ T157-2009), World J. Integr. Trad. West Med. 4 (2009) 303–304. [6] Y.C. Wong, M.C. Pang, Initial validation of the Yin-Yang assessment questionnaire for persons with diabetes mellitus, World J. Diabetes 11 (2015) 1198–1206. [7] C. Xia, Q.B. Zhu, F. Huang, J.H. Huang, H.D. Chen, M.J. Chen, W. Gu, B. Li, F.F. Fang, L.N. Wu, Traditional Chinese medicine constitution types in 127 elderly patients with insomnia: an investigation in communities of Yangpu District, Shanghai, Zhong Xi Yi Jie He Xue Bao 10 (8) (2012) 866–873. [8] Q. Wang, X.J. Ren, S.L. Yao, H.D. Wu, Clinical observation on the endocrinal and immune functions in subjects with yin-deficiency constitution, Chin. J. Integr. Med. 16 (1) (2010) 28–32. [9] K.G. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith Jr, International Diabetes Federation Task Force on Epidemiology, Prevention, Hational Heart, Lung, Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the study of obesity, Circulation 16 (2009) 1640–1645. [10] R.H. Eckel, K.G. Alberti, S.M. Grundy, P.Z. Zimmet, The metabolic syndrome, Lancet 9710 (2010) 181–183. [11] Y.P. Wang, E. Wat, C.M. Koon, C.W. Wong, D.W. Cheung, P.C. Leung, Q.S. Zhao, K.P. Fung, C.B. Lau, The beneficial potential of polyphenol-enriched fraction from Erigerontis Herba on metabolic syndrome, J. Ethnopharmacol. 187 (July (1)) (2016) 94–103. [12] C.-I. Tsai, Y.-C. Su, S.-Y. Lin, I.T. Lee, C.-H. Lee, T.-C. Li, Reduced health-related quality of life in body constitutions of Yin-Xu, and Yang-Xu, stasis in patients with type 2 diabetes: taichung diabetic body constitution study, Evid.-Based Complementary Altern. Med. 2014 (2014) 1–10. [13] S.-H. Kuo, H.-L. Wang, T.-C. Lee, T.-F. Chan, F.-H. Chou, L.-M. Chen, W.-T. Lin, Traditional Chinese medicine perspective on constitution transformations in perinatal women: a prospective longitudinal study, Women Birth 28 (2015) 106–111. [14] T. Yu, Z. Zhang, L. Xie, X. Ke, Y. Liu, The influence of traditional Chinese medicine
Declaration Ethical approval and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all patients before the study, and this study was approved by the Ethics Committee of Huashan Hospital, Shanghai, China (approval number 2009109). The methods were carried out in accordance with the approved guidelines. Consent for publication All authors read and approved the final manuscript. Availability of data and material The datasets generated and/or analysed during the current study are not publicly available due to private information but are available from the corresponding author on reasonable request. Dataset are from the study whose authors may be contacted at Center of Bioinformatics and Biostatistics, Institutes of Integrative Medicine, Fudan University. Funding Grants from the Institutes of Integrative Medicine of Fudan 35
European Journal of Integrative Medicine 14 (2017) 32–36
F. Xu et al.
[15]
[16]
[17]
[18] [19]
[20] [21]
[22]
patients, Zhongguo Zhong Xi Yi Jie He Za Zhi 33 (February (2)) (2013) 199–204. [23] J. Zhao, Y. Ding, Y. Wang, J. Li, Trinity of physique differentiation, diagnosis of disease and syndrome differentiation and clinical practice of diabetes, Zhonghua Zhong Yi Yao Za Zhi 24 (2009) 994–998. [24] W.Y. Jiang, Therapeutic wisdom in traditional Chinese medicine: a perspective from modern science, Trends Pharmacol. Sci. 26 (2005) 558–563. [25] G. Kressel, B. Trunz, A. Bub, O. Hülsmann, M. Wolters, R. Lichtinghagen, D.O. Stichtenoth, A. Hahn, Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk, Atherosclerosis 202 (1) (2009) 263–271. [26] A. Tedgui, Z. Mallat, Cytokines in atherosclerosis: pathogenic and regulatory pathways, Physiol. Rev. 86 (2) (2006) 515–581. [27] S. Crunkhorn, Metabolic disorders. Hormone conjugate combats metabolic syndrome, Nat. Rev. Drug Discov. 15 (2016) 821. [28] B. Xu, H. Yang, Z. Wang, T. Yang, H. Guo, P. Cheng, W. He, M. Sun, H. Chen, Y. Duan, Elevated thyroid stimulating hormone levels are associated with metabolic syndrome in a Chinese community-based population of euthyroid people aged 40 years and older, J. Biomed. Res. 30 (6) (2016) 476. [29] A. Carrier, Metabolic Syndrome and Oxidative Stress: A Complex Relationship, Antioxid. Redox Signal. 26 (9) (2017) 429–431. [30] B. Ou, D. Huang, M. Hampsch-Woodill, J.A. Flanagan, When east meets west: the relationship between yin-yang and antioxidation-oxidation, FASEB J. 17 (2) (2003) 127–129.
constitutions on the potential repair capacity after osteonecrosis of the femoral head, Complement. Ther. Med. 29 (2016) 89–93. Y-l Feng, G-y Zheng, C-q. Ling, The investigation of the correlation between metabolic syndrome and Chinese medicine constitution types in senior retired military personnel of the People’s Liberation Army, Chin. J. Integr. Med. 18 (2012) 485–489. J. Liu, F. Xu, N. Mohammadtursun, Y. Lv, Z. Tang, J. Dong, The analysis of constitutions of traditional Chinese medicine in relation to cerebral infarction in a Chinese sample, J. Altern. Complement. Med. (2017), http://dx.doi.org/10.1089/ acm.2017.0027 [Epub ahead of print]. H.J. Chen, Y.J. Lin, P.C. Wu, W.H. Hsu, W.C. Hu, T.N. Wu, F.P. Chen, Y.L. Lin, Study on Yang-Xu using body constitution questionnaire and blood variables in healthy volunteers, Evid. Based Complement Alternat. Med. 2016 (2016) 9437382. S. Golbidi, A. Mesdaghinia, I. Laher, Exercise in the metabolic syndrome, Oxid. Med. Cell Longev. 2012 (2012) 349710. S.H. Kuo, H.L. Wang, T.C. Lee, T.F. Chan, F.H. Chou, L.M. Chen, W.T. Lin, Traditional Chinese medicine perspective on constitution transformations in perinatal women: a prospective longitudinal study, Women Birth 28 (2015) 106–111. Y.M.Y. Jiang, Y. Yang, et al., Discussion on diabetes in terms of Yang deficiency, Med. World (2006) 114. K. Choi, J. Lee, J. Yoo, E. Lee, B. Koh, J. Lee, Sasang constitutional types can act as a risk factor for insulin resistance, Diabetes Res. Clin. Pract. 91 (March (3)) (2011) e57–e60. S.H. Han, K.Z. Li, J.M. Zheng, Z.X. Zheng, M.C. Lin, M.Y. Xu, Z.C. Yue, Study on the distribution of Chinese medical constitutions of hypertension complicated diabetes
36