| Objective: to discover the presence of difference in metabolic substance between type-2 diabetes and its microvascular complication through a metabonomic detection and analysis on the serum and urine of normal people,patients with type-2 diabetes,patients with diabetic retinopathy(those who have a deficiency of both qi and yin and who have either of them or who have concurrent syndromes)and patients with diabetic nephropathy(those who have a deficiency of both qi and yin and who have either of them or who have concurrent syndromes);to explore the underlying pathogenesis of diabetic microvascular complication at the level of metabolic substance,meanwhile,to preliminarily reveal the biological material basis of the syndromes related to type-2 diabetes and its microvascular complication on the basis of syndrome-element analysis and method of multivariate statistical analysis in order to provide a theoretical basis for the objectification and normalization of TCM syndrome.Method: 99 cases of normal subject,96 cases of type-2 diabetic patient,114 cases of patients with diabetic retinopathy(those who have a deficiency of both qi and yin and who have either of them or who have concurrent syndromes)and 43 cases of patients with diabetic nephropathy(those who have a deficiency of both qi and yin and who have either of them or who have concurrent syndromes)were admitted in four hospitals all over China,the basic information and information about TCM symptoms and signs of patients were entirely collected,the GC-MS technological platform was used to test the patients’ serum and urine,the control-NIST standard compound spectrum library and Fiehn lab database were used to identify the compounds in the spectrogram being collected,and the PCA analysis、PLS-DA analysis and OPLS-DA analysis were used to screen the differential compounds.Besides,by the use of syndrome-element analysis,cluster analysis and PCA analysis,the syndromes of patients with type-2 diabetes and the ones with diabetic microvascular complications(patients with diabetic retinopathy and ones with diabetic nephropathy)were classified and determined in nature,based on which,the differential metabolic substances in the serum and urine of patients with various types of syndrome were identified by the use of metabonomics technology.Result: 1)the difference in metabolic characteristics of serum and urine between the normal people,patients with type-2 diabetes,patients with diabetic retinopathy(patients with diabetic retinopathy and ones with diabetic nephropathy)and patients with diabetic nephropathy(patients with diabetic retinopathy and ones with diabetic nephropathy)was statistically significant,the change in metabolic substance mainly involves the amino acid metabolism,glycometabolism,cholesterol metabolism,lipid metabolism,energy metabolism,urea metabolism,and metabolic pathways related to oxidative stress,specifically manifested as the change in metabolic pathways like phosphopentose,sorbitol,gluconeogenesis,tricarboxylic acid cycle,fatty acid metabolism,ornithine cycle,uric acid metabolism and phenylalanine metabolism.The differences in the metabolic characteristics of serum and urine between the patients with type-2 diabetes who had fire excess from yin deficiency,the ones who had stagnation-heat in liver and stomach,the ones who had yin-yang deficiency and the ones who had deficiency of both qi and yin were statistically significant.The differential metabolites in serum mainly include alanine,lysine,phenylalanine,proline,serine,aspartic acid,glutamine,glutamic acid,glycine,threonine,asparagine,tryptophan,isoleucine,leucine,valine,galactose,cysteine and homocystine,the amino acid metabolism,glycometabolism and oxidative stress-related metabolic change were involved.the differential metabolites in urine mainly include glycine,tyrosine,threonine,histidine,valine,isoleucine,leucine,lyxose,uracil,pyroglutamic acid,threonic acid,glycolic acid and inositol,the metabolic change in amino acid,carbohydrate,pyrimidine,bile acid,phosphoinositide and oxidative stress were involved.The differences in metabolic characteristics of serum and urine between the patients with diabetic microvascular complications who had deficiency of both qi and yin,the ones who had deficiency of both qi and yin coupled with blood stasis(coupled with stagnation of qi),the ones who had deficiency of both qi and yin coupled with deficiency of yang and blood stasis,the ones who had deficiency of both qi and yin coupled with deficiency of yang,the ones who had deficiency of both qi and yin coupled with phlegm turbidity and blood stasis(coupled with water-dampness/stagnation of qi),the ones who had deficiency of both qi and yin coupled with phlegm turbidity(and water-dampness),and the ones who had deficiency of both qi and yin with a predisposition of blood deficiency were all statistically significant.The differential metabolites in serum mainly include alanine,aspartic acid,glycine,lysine,phenylalanine,serine,tyrosine,threonine,leucine,valine,tagatose,galactose,gluconic acid,pyroglutamic acid,cysteine,homocysteine and uric acid,mainly involving the change in pathways related to amino acid metabolism,glycometabolism and oxidative stress.However,the significantly differential metabolites in urine of patients from groups of different syndrome mainly include the glycine,hippuric acid,allose,lactose,maltose,RNA,sorbitol,malic acid,fumaric acid,glycolic acid,cysteine,homocysteine,uric acid,xanthine and uracil,mainly involving the amino acid metabolism,glycometabolism,TCA cycle,bile acid metabolism,oxidative stress and change in pathways related to pyrimidine degradation.Conclusion: the differences in metabolites in serum and urine between the normal people,type-2 diabetic patients,patients with diabetic retinopathy(patients with diabetic retinopathy and ones with diabetic nephropathy)and patients with diabetic nephropathy(patients with diabetic retinopathy and ones with diabetic nephropathy)were all statistically significant.The differences in metabolites in serum and urine between the type-2 diabetic patients who had different syndromes were all statistically significant,The differences in metabolites in serum and urine between the patients with diabetic microvascular complications(those who had deficiency of both qi and yin as well as those who had partial syndromes and those who had concurrent syndromes)who had different partial syndromes and who had different concurrent syndromes were all statistically significant. |
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