| Part Ⅰ Literature ResearchThe section of modern medical were reviewed around the epidemiology,definition and diagnosis,pathogeny,pathogenesis,prevention principle and treatment principle of diabetes mellitus and metabolic syndrome.The section of Traditional Chinese medicine were reviewed around the theoretical research and recipe-medicines research of diabetes mellitus with syndrome of intermingled phlegm and blood stasis.The section of Hedan tablets were reviewed around pharmacological effect,clinical research,precautions for use.Under the guidance of Professor Ni Qing’s academic thoughts,the review is summarized and prospected.Part Ⅱ Discussion on SyndromeObjective:To explore subtype classification of syndrome of intermingled phlegm and blood stasis in diabetes mellitus and the clinical characteristics of the subtypes;to explore the correlation of subtype and physicochemical indicators;to summarize the characteristics and the evolution law of syndrome of intermingled phlegm and blood stasis in diabetes mellitus.Methods:Selected 231 cases that met the diagnosis of diabetic with sputum turbidity syndrome and blood stasis syndrome,collected their general data(gender,age,disease course,BMI),symptom data(symptoms,signs,tongue image,and pulse image),physicochemical indexes(HbA1c,FBG,SBP,DBP,PP,TC,TG,HDL-C,LDL-C,UA).According to TCM syndrome type determination criteria and the ’six-step treatment mode for type 2 diabetes based on combination of diseases and syndromes’proposed by the tutor,Professor Ni Qing.Summarized the number of inductive subtypes,explored the basic characteristics of patients with subtypes,explored the correlation between subtype and physicochemical indexes,summarized the characteristics of syndrome of intermingled phlegm and blood stasis in diabetes mellitus.Used cluster analysis method to summarize the main symptoms groups,extracted the common accompanied syndrome,judged the correlation between the accompanied syndrome and subtype,analyzed the correlation of accompanied syndrome and clinical indicators,to summarize the evolution law of the syndrome.Results:1.There are 3 subtypes in diabetes mellitus with syndrome of intermingled phlegm and blood stasis:type of phlegm turbid accompanied with blood stasis,type of intermingled phlegm and blood stasis,type of blood stasis accompanied with phlegm-turbidity.2.Study on the general characteristics of the subtypes(1)Course of disease:Most of the patients had a course of more than 10 years.The patients with type of blood stasis accompanied with phlegm-turbidity had the longest course of disease,followed by the patients with type of intermingled phlegm and blood stasis,and the patients with type of phlegm turbid accompanied with blood stasis had the shortest course of disease.There was significant difference betweem subtypes and phlegm turbidity syndrome,or betweem subtypes and blood stasis syndrome(P<0.05),but there was no significant difference among the subtypes(P>0.05).(2)Age:Most of the patients were aged from 50 to 65 years old.The patients with type of blood stasis accompanied with phlegm-turbidity were the oldest,followed by the patients with type of intermingled phlegm and blood stasis,and the patients with type of phlegm turbid accompanied with blood stasis were the youngest.There was a statistically significant difference betweem subtypes and phlegm turbidity syndrome,or betweem subtypes and blood stasis syndrome(P<0.05),but there was no statistically significant difference among the subtypes(P>0.05).(3)BMI:The patients were generally overweight or obese.The type of phlegm turbid accompanied with blood stasis had the highest BMI,followed by the patients with type of intermingled phlegm and blood stasis,The type of blood stasis accompanied with phlegm-turbidity had the lowest BMI.There was no significant difference in BMI among the subtypes(P>0.05).3.Study on the correlation between subtypes and physicochemical indicators(1)Correlation between subtypes and HbA1c,FBG:HbA1c increased most significantly in patients with type of intermingled phlegm and blood stasis,and FBG increased most significantly in patients with type of blood stasis accompanied with phlegm-turbidity,but there was no significant difference in HbAlc and FBG among subtypes(P>0.05).(2)Correlation between subtypes and SBP,DBP,PP:SBP,DBP,PP were relatively high in patients with type of phlegm turbid accompanied with blood stasis,SBP,DBP,PP were relatively low in patients with type of blood stasis accompanied with phlegm-turbidity,but there was no significant difference in SBP,DBP,PP among subtypes(P>0.05).(3)Correlation between subtypes and TC,TG,LDL-C,HDL-C:TC,TG,LDL-C increased most significantly in patients with type of phlegm turbid accompanied with blood stasis,and HDL-C decreased most significantly in patients with type of blood stasis accompanied with phlegm-turbidity.There was significant difference in TG and LDL-C between type of phlegm turbid accompanied with blood stasis and type of intermingled phlegm and blood stasis(P<0.05),there was significant difference in HDL-C among subtypes(P<0.05).(4)Correlation between subtypes and UA:Among obese patients(BMI≥28kg/m2),UA increased most significantly in patients with type of phlegm turbid accompanied with blood stasis.In male patients,there was significant difference in UA between type of phlegm turbid accompanied with blood stasis and type of blood stasis accompanied with phlegm-turbidity(P<0.05);In female patients,there was no significant difference in UA among subtypes(P>0.05).4.The study of syndrome evolution(1)Four groups of clusters were obtained by cluster analysis:The first group included syndrome of liver depression transforming into fire,syndrome of sputum-heat stagnating in spleen and Sputum-dampness stagnating in spleen;The second group includes syndrome of Yang deficiency of heart and kidney,syndrome of deficiency of both Qi and Yin;The third group includes syndrome of spleen deficiency and dampness accumulation,syndrome of Qi deficiency of spleen and kidney;The fourth group includes syndrome of Yin deficiency of liver and kidney.(2)Common accompanied syndrome in subtype:Qi-deficiency syndrome,viscera heat syndrome,spleen deficiency syndrome,kidney Yin deficiency syndrome.The proportion of spleen deficiency syndrome and viscera heat syndrome was higher in patients with type of phlegm turbid accompanied with blood stasis,the proportion of kidney Yin deficiency syndrome was higher in patients with type of intermingled phlegm and blood stasis,and the proportion of Qi-deficiency syndrome was higher in patients with type of blood stasis accompanied with phlegm-turbidity.(P<0.05).(3)The Correlation between accompanied syndrome and physicochemical indexes:HbAlc,FBG,TC and LDL-C increased was significantly correlated with viscera heat syndrome(P<0.05),while SBP,HDL-C and UA were significantly correlated with kidney-Yin deficiency syndrome(P<0.05).Conclusion:There are 3 subtypes in diabetes mellitus with syndrome of intermingled phlegm and blood stasis:type of phlegm turbid accompanied with blood stasis,type of intermingled phlegm and blood stasis,type of blood stasis accompanied with phlegm-turbidity.Patients with this syndrome are generally overweight or obese,and the age is mainly distributed in 55 to 65 years old,and the course of the disease is more than 10 years.There are four accompanied syndrome in subtypes:the type of phlegm turbid accompanied with blood stasis combining viscera heat syndrome,The type of phlegm turbid accompanied with blood stasis combining spleen deficiency,The type of intermingled phlegm and blood stasis combining kidney Yin deficiency,the type of blood stasis accompanied with phlegm-turbidity combining Qi deficiency.Among the diabetic patients with three subtypes of syndrome,patients with type of phlegm turbid accompanied with blood stasis was younger,the disease course was shorter,and the blood lipid,blood pressure and uric acid indicators are relatively high.In diabetic patients with viscera heat syndrome,the blood glucose and blood lipid indicators are relatively high,Kidney Yin deficiency syndrome.In diabetic patients with syndrome of deficiency of kidney Yin,the blood pressure and uric acid indicators are relatively high.The evolution of the syndrome of intermingled phlegm and blood stasis in diabetic patients include the dysfunction of spleen and kidney,stagnated Qi transforming into fire accompanied impairment of Yin.Part Ⅲ Clinical ObservationObjective:This study aims to use a randomized,single blind,parallel control research method;to explore the improvement of clinical symptoms and physicochemical indexes in diabetic patients with syndrome of intermingled phlegm and blood stasis after taking Hedan tablets;to analyze the efficacy and safety of Hedan tablets on this syndrome and its subtypes.Methods:A randomized,single-blind,parallel control method was used in this study.From December 2021 to April 2022,80 diabetic patients that met the diagnosis and inclusion criteria were included from the endocrinology clinic and wards of Guang’anmen Hospital,of which 40 were in the treatment group(Hedan tablets with conventional therapy)and 40 were in the control group(placebo with conventional therapy).The course of intervention was 6 weeks,Observed the TCM syndrome points,main efficacy indicators(FINS、CpS0、FBG、HOMA-IR),secondary efficacy indicators(TC,TG,HDL-C,LDL-C,SBP,DBP,UA),general efficacy indicators(BMI,abdominal circumference),abdominal ultrasound,safety indicators(AST、ALT,ECG)before and after treatment between the two groups,evaluated the efficacy and safety of Hedan tablets in diabetic patients with syndrome of intermingled phlegm and blood stasis and its subtype.Results:1.Efficacy evaluation of Hedan tablets in improving TCM syndromes(1)Single symptom score:there was no significant difference between the two groups before treatment(P>0.05),but there was significant difference between the two groups after treatment(P<0.05).There was significant difference in the symptoms of the treatment group before and after treatment(P<0.05),but there was no significant difference in the control group before and after treatment(P>0.05),suggesting that the improvement of clinical symptoms in the treatment group was higher than that in the control group.(2)Improvement rate of individual symptoms:After 6 weeks of treatment,the improvement rate of chest tightness,mouth adhesion,limb numbness,dry mouth,cold limbs,abdominal distension,headache,heavy limb sleepiness,frequent nocturia,and constipation symptoms was higher than that in the control group,There was significant difference between the two groups(P<0.05);There was no significant difference between the two groups in improvement rate of palpitations,dizziness,chest pain,insomnia,and limb pain symptoms(P>0.05);There was significant difference in the symptom improvement rate in treatment group before and after treatment(P<0.05).(3)Improvement rate of syndrome:The improvement rate of syndrome was 77.5%in the treatment group and 30.8%in the control group(P<0.05);Comparison of the improvement rate in subtype syndrome:the improvement rate of type of phlegm turbid accompanied with blood stasis was 78.6%;The improvement rate of syndrome of intermingled phlegm and blood stasis was 78.2%;The improvement rate of type of blood stasis accompanied with phlegm-turbidity was 66.7%.2.Efficacy evaluation of Hedan tablets in main indicators:There was significant difference in IRI0、CpS0 and HOMA-IR between the two groups after treatment(P<0.05),suggesting that Hedan tablets could increase fasting serum insulin level,fasting C-peptide level and improve the degree of insulin resistance(P<0.05);There was no significant difference in FBG level between the two groups after treatment(P>0.05),but there was significant difference in the number of cases with FBG reaching the standard(P<0.05),suggesting that Hedan tablets can reduce the fasting blood glucose level to some extent.3.Efficacy evaluation of Hedan tablets in secondary indicators(1)Blood lipid:There was significant difference in TG level between the two groups after treatment(P<0.05);There was no significant difference in the levels of TC and LDL-C between the two groups after treatment(P>0.05),but there was significant difference in the number of cases with TC and LDL-C reaching the standard(P<0.05),suggesting that Hedan tablets can reduce the levels of TC and LDL-C to some extent;There was no significant difference in HDL-C level and the number of cases reaching the standard between the two groups after treatment(P>0.05),suggesting that Hedan tablets had no obvious effect on HDL-C.(2)Blood pressure:After 6 weeks of treatment,the number of cases with SBP and DBP reaching the standard in the treatment group was slightly higher than that in the control group,but there was no statistical difference between the two groups after treatment(P>0.05),suggesting that Hedan tablet may have a certain effect on blood pressure,but the effect was not significant.(3)Uric acid:After 6 weeks of treatment,the UA compliance rate in the treatment group was slightly higher than that in the control group,but there was no significant difference(P>0.05),suggesting that Hedan tablets may have some effect on UA,but the effect was not significant.(4)Hepatic adipose infiltration:After 6 weeks of treatment,the number of patients with fatty liver in the treatment group had no statistical difference compared with that before treatment(P>0.05),but the number of patients with fatty liver in the treatment group was less than that in the control group(P<0.05),suggesting that Hedan tablets could reduce the degree of fatty liver to some extent.4.Efficacy evaluation of Hedan tablets in general indicators:There was no significant difference in BMI between the two groups after treatment(P>0.05),suggesting that Hedan tablets had no obvious effect in reducing BMI;There was significant difference in abdominal circumference between the two groups after treatment(P>0.05),suggesting that hodan tablets are highly effective in improving abdominal obesity.5.Safety evaluation of Hedan tablets:No adverse reactions were occurred in the treatment group and the control group during the study period.Conclusion:The results of this study showed that Hedan tablets can effectively improve the clinical symptoms of diabetic patients with syndrome of intermingled phlegm and blood stasis.Hedan tablets has the most obvious effect on type of phlegm turbid with blood stasis;Hedan tablets have good results in improving fasting insulin levels,reducing insulin resistance,reducing TG levels,and reducing abdominal obesity;Hedan tablets can also lower the levels of FBG,TC,LDL-C and reduce fatty liver;Hedan tablets have no obvious effect on HDL-C,SBP,DBP,UA and BMI.No abnormal safety indicators and adverse reactions were found during the study period,which indicated that Hedan tablets are well safe. |
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