Human Serum Metabonomic Analysis Reveals Progression For High Blood Pressure In Type 2 Diabete Mellitus

Background:Type 2 diabetes mellitus(T2DM)is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period,80% to 90% of patients with T2 DM will develop with high blood pressure(HBP),which further easily exacerbates irreversible organ damage.Understanding the metabolic basis of HBP is essential to facilitate early diagnosis and personalized treatments of diabetic complications.Objective:To understand the metabolic basis of type 2 diabetes mellitus and high blood pressure,and to elucidate the relevant mechanisms for the early diagnosis and individualized treatment of irreversible organ injury.Methods:Here,4298 participants recruited in the study were followed up to 3-years.34 patients were picked up,their primary disease was T2 DM and later developed with HBP in one year.Differences in metabolomic profiling of serum between T2 DM,T2DM+HBP and healthy people(subjects with T2 DM initially,n=34;and then with T2DM+HBP one year later,n=34;healthy controls=HC,n=30)were investigated using ultrahigh-pressure liquid chromatography quadrupole time of flight mass spectrometry(UHPLC-Q-TOF MS)and multivariate data analysis.Altered pathways and pivotal proteins and metabolites were searched by integrative analysis of proteomics and metabolomics data.Results:The study showed a clear distinction in metabolomic profiles between T2 DM and T2DM+HBP when using OPLS-DA with both positive and negative electrospray ionization mode.Corresponding to pyroglutamic acid,L-isoleucine,L-glutamic acid,succinylacetone,sphinganine,LysoPC(18:1(9Z)),Cer(d18:0/16:0),Cer(d18:0/16:0),citric acid,12S-HHT and linoleic acid.IPA analysis of these 11 metabolites showed that they were significantly associated with the processes of injury and abnormality of the body,nervous system disease,gastrointestinal disease,cell death and survival,cell development,organism development,cell growth and proliferation,hepatobiliary system disease,cancer and protein synthesis.IPA analysis software was used to connect related metabolic pathways,and relevant metabolic pathways were screened out.This is mainly about the mechanism of disease development in patients with type 2 diabetes mellitus complicated with hypertension.Biological pathways were screened by log(p-value)and Ratio value,and biological pathways related to two or more biological small molecule differential metabolites were found.A total of four related pathways were obtained,which were: ?-glutamyl Cycle,Isoleucine Degradation I,tRNA Charging,Sirtuin Signaling Pathway.Conclusion:Eleven metabolites were selected from the serum of patients with type 2 diabetes mellitus to elucidate the mechanism of HBP and to predict related target organ injury.Among them,L-isoleucine,L-glutamic acid played an important role,which reflected the metabolic differences between healthy controls and T2 DM which then with T2DM+HBP one year later people,which may be important for future clinical diagnosis,treatment and assessment of the therapeutic effect on T2 DM developed with HBP.