| Objective: 1.To explore the distribution of TCM syndromes of insulin resistance in type 2diabetes mellitus,and analyze the clinical characteristics of different syndromes in combination with relevant clinical indicators,so as to provide scientific basis for clinical syndrome differentiation and treatment of insulin resistance in type 2 diabetes mellitus.2.To investigate whether Gypenoside XLIX can improve insulin resistance and its possible mechanism.Methods: 1.Clinical study: This study adopts retrospective case study to collect the TCM four diagnostic information and clinical data of 120 patients with insulin resistance of type2 diabetes mellitus included in this study,including age,course of disease,BMI,FPG,FINS,TG,CHOL,LDL,Hb A1 c and other indicators.SPSS software was used to establish the database of the four diagnostic information items of these 120 patients.Ward’s method and Squared Euclidean Distance in the system clustering method were used to carry out clustering analysis.According to the distribution of the clustered symptom items,a group of experts composed of three chief physicians discussed the initial model of clustering analysis and determined the TCM syndrome classification of insulin resistance in type 2 diabetes mellitus.Then,through the specific analysis of the clinical symptoms of patients to determine their TCM syndrome types,and finally summarize and analyze the clinical indicators of each syndrome type,and make comparisons between different syndrome type groups,as well as exploring sensitive indicators related to insulin resistance in different syndrome type groups.2.Experimental study: The insulin resistance model of rats was established by intravenous lipid infusion,and whether Gyp-XLIX could improve insulin resistance was verified by hyperinsulinemic-euglycemic clamping test.After the test was completed,liver,muscle and adipose tissue were collected and related tests,such as western blotting and polymerase chain reaction(PCR)were conducted to explore its possible mechanism of action.Results: 1.Clinical research:(1)the distribution of the four diagnostic Information: The top ten symptoms of frequency distribution of insulin resistance in type 2 diabetes are: dry mouth and sticky mouth,numbness of limbs,skin pruritus,blurred vision,dry eyes,asthenia,easy hunger,anorexia,insomnia,dizziness,dark red tongue,yellow and greasy coating,and pulse appearance frequency from high to low is string pulse,smooth pulse,counting pulse,astringent pulse,sunken pulse,thread pulse and moist pulse.(2)Cluster analysis results: The4 types of TCM syndromes are liver and stomach stagnation and heat syndrome,phlegm and blood stasis and heat accumulation syndrome,deficiency of qi and yin,and deficiency of yin and yang.The distribution of each syndrome type is: liver and stomach stagnation and heat syndrome in 35 cases(29.90%),phlegm and blood stasis and heat accumulation syndrome in 55 cases(47.00%),qi and yin deficiency syndrome in 17 cases(14.55%),yin and yang deficiency syndrome in 10 cases(8.55%),in addition,the TCM syndrome differentiation of3 patients does not belong to the above four TCM syndrome types.(3)comparison of clinical indicators of different syndrome types:(1)As seen from the course of disease in each group,the course of disease in the liver-stomach stagnation-heat syndrome type group is the shortest,with statistical significance compared with other three types(P<0.01).The course of disease of yin-yang deficiency type is longer than that of phlegm-blood stasis-heat accumulation type and qi-yin deficiency type,with statistically significant difference(P<0.01).(2)In all TCM syndrome types,the HOMA-IR value of phlegm-stasis-heat accumulation syndrome type group is the highest,which has statistical significance compared with other three groups(P<0.01 or P<0.05),while the HOMA-IR value of yin-yang deficiency syndrome type group is the lowest,which has significant statistical difference compared with qi-yin deficiency group(P<0.01),but there is no statistical difference compared with liver-stomach stasis-heat group(P>0.05).(3)Among the TCM syndrome types,the phlegm-stasis-heat accumulation syndrome type group has the highest BMI and Hb A1 c,and the difference is statistically significant compared with other syndrome types(P<0.01).(4)TG and LDL levels were increased in turn in the liver-stomach stagnation heat,yin-yang deficiency,qi-yin deficiency and phlegm-stasis heat accumulation group,while CHOL levels were increased in turn in the yin-yang deficiency,liver-stomach stagnation heat,qi-yin deficiency and phlegm-stasis heat accumulation group.Among them,TG,CHOL and LDL levels in phlegm-stasis heat accumulation group were the highest,significantly higher than those in other groups,with statistical significance(P<0.01 or P<0.05).(5)In the liver-stomach stagnation-heat syndrome group,TG,LDL and HOMA-IR are positively correlated(r=0.43,P<0.05;r=0.26,P<0.05).In the phlegm-stasis-heat accumulation group,BMI,Hb A1 c,TG,CHOL,LDL were positively correlated with HOMA-IR(r=0.45,P<0.05;r=0.31,P<0.05;r=0.52,P<0.05;r=0.38,P<0.05;r=0.43,P<0.05).In the group of deficiency of qi and yin and deficiency of yin and yang,BMI,Hb A1 c,TG,CHOL,and LDL have no significant correlation with HOMA-IR,P>0.05.2.Experimental study:(1)Compared with normal saline infusion group,the plasma free fatty acid(FFA)content in lipid group and lipid+Gyp-XLIX group increased significantly due to the infusion of lipid.(2)Compared with normal saline infusion,lipid infusion significantly reduced the steady glucose infusion rate(SSGIR)(p<0.001),suggesting the establishment of insulin resistance model.However,compared with lipid infusion group,SSGIR in lipid+Gyp-XLIX group is significantly increased(p<0.01),indicating Gyp-XLIX can relieve insulin resistance caused by lipid infusion.(3)In liver and muscle tissues,GypXLIX can significantly reduce the increase in phosphorylation expression of insulin receptor substrate(IRS1)serine 307(Ser307)site and the decrease in phosphorylation expression of phosphatidylinositol 3 kinase(PI3K)P85 site and protein kinase B(Akt)473 site caused by lipid infusion,indicating that Gyp-XLIX can reduce the damage of lipid infusion on insulin signaling pathway.(4)In liver and muscle tissues,Gyp-XLIX can significantly reduce IκBαphosphorylation expression,ubiquitination degradation and NF-κB nuclear translocation caused by lipid infusion,indicating that Gyp-XLIX reduced the transmission activity of IκBα/NF-κB signal pathway stimulated by lipid infusion.(5)The infusion of lipid significantly increased the m RNA expression of TNF-α and IL-6 in liver tissue,and also significantly increased the m RNA expression of TNF-α and IL-1β in muscle tissue.In addition,due to the infusion of lipid,the m RNA expression of IL-1β in liver tissue and IL-6in muscle tissue had an increasing trend compared with normal saline group,but there was no statistical difference.Gyp-XLIX can significantly reduce the increase of expression of these inflammatory factors.Conclusions: 1.Clinical research: Insulin resistance is the key pathological feature of type2 diabetes mellitus,which causes the occurrence of type 2 diabetes mellitus and enhanced the development of type 2 diabetes mellitus.As an important factor for its progress,it is necessary to intervene and treat insulin resistance as soon as possible.According to our research,insulin resistance in type 2 diabetes can be divided into four syndrome types: liver and stomach stagnation heat,phlegm and blood stasis heat accumulation,deficiency of qi and yin,and deficiency of yin and yang.Symptoms of different syndrome types show different manifestations and their priorities are different.In clinical practice,we should not only "macroscopically differentiation of symptoms and signs",but also "microcosmic differentiation of symptoms and signs" according to the clinical symptoms of patients,including the manifestation of tongue and pulse,and the basic theory of traditional Chinese medicine.On this basis,we should also "microcosmic differentiation of symptoms and signs",and comprehensively consider the implementation of the treatment plan based on the clinical indicators of patients,combined with various factors such as their constitution,course of disease,onset age,etc.2.Experimental study: Gypenoside XLIX can obviously improve insulin resistance caused by lipid infusion and reduced the damage of lipid infusion on insulin signaling pathway.The beneficial effect of Gyp-XLIX may be related to its ability to reduce local inflammatory reactions in liver and muscle tissues caused by lipid infusion.3.Syndrome differentiation and treatment is the essence of traditional Chinese medicine.Through the clinical research,the classification of TCM syndromes of insulin resistance of type 2 diabetes mellitus has been deeply discussed,which provided scientific basis for its clinical treatment based on syndrome differentiation.Disease differentiation and treatment is a supplement and improvement of syndrome differentiation and treatment.Practical experience tells us that if the treatment of insulin resistance in type 2 diabetes mellitus can be based on traditional syndrome differentiation and treatment,appropriate addition of some drugs with a clear effect of improving insulin resistance,and the combination of syndrome differentiation and disease differentiation and treatment can greatly increase the clinical efficacy.Through the research in the experimental part,we preliminarily confirmed the feasibility of Gypenoside XLIX as the agent for improving insulin resistance,providing new insights and ideas for a comprehensive understanding of the pharmacological effects of traditional Chinese medicine Gynostemma Pentaphyllum and the development of drugs for improving insulin resistance. |
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