The Relationship Between Plasma Amino Acids And Hypertriglyceridemia In Patients With Diabetes

Background:Robust clinical evidence demonstrates that statin-induced reductions in low-density lipoprotein cholesterol(LDL-C)lead to substantial reductions in cardiovascular disease(CVD)risk in both the primary and secondary prevention settings.Therefore,in patients at high cardiovascular risk due to dyslipidemia,the majority of current guidelines recommend LDL-C as a primary treatment target,with statins as first-line therapy.Despite significant LDL-C lowering with statin therapy,substantial residual cardiovascular risk often remains.This residual risk is thought to be due,in part,to inadequate reduction of LDL-C for a given level of risk,low levels of high-density lipoprotein cholesterol(HDL-C),and/or high levels of triglycerides(TG).Additionally,there is increasing evidence that triglycerides,may be more strongly associated with atherosclerotic risk than LDL-C alone.So instead of intensive use of statins,combined medication may be a better option for patients with poor response to current statin therapy.Additional efforts are needed to identify these subjects and explore potential new targets for their TG lowering.Amino acids are important components for protein synthesis and play significant roles in a number of physiological processes including energy production,inflammation,signaling,insulin resistance,redox,and so on.In this connection,amino acids were identified as new biomarkers of chronic conditions such as diabetes,CVD,and obesity.Although the relationships between amino acids and triglycerides were yet completely clarified,their associations have been investigated in many studies.Compared with healthy controls,patients with abnormal BMI or non-alcoholic fatty liver disease have profound perturbation of amino acid metabolism.Several cross-sectional and longitudinal studies also showed that amino acid signature significantly predicted future hypertriglyceridemia in children.In order to clarify whether there is a correlation between plasma amino acid levels and hypertriglyceridemia,a cross-sectional analysis of two independent clinical cohorts was carried out in an attempt to find out whether plasma amino acids in diabetic patients are related to residual high triglycerides under statin treatment.Esteremia is related,and whether it can be used as a potential new therapeutic target.Objective:1)Whether there are differences in amino acid metabolites between normal TG diabetes patients and HTG diabetes patients;2)When LDL-C level reached the treatment standard(LDL-C<2.6mmol/L),whether there was a difference in amino acid metabolites between normal TG diabetes patients and HTG diabetes patients;3)Whether the different amino acid metabolites are associated with the risk of HTG in diabetic patients treated with statins.Methods:Two independent cross-sectional hospital based cohorts.Liaoning Medical University First Affiliated Hospital(LMUFAH,n=146)and the Second Affiliated Hospital of Dalian Medical University(SAHDMU,n=294)were included in current analysis.Hypertriglyceridemia was defined as triglyceride ≥ 1.7 mmol/L;well-controlled LDL-C was defined as <2.6 mmol/L.The adjusted ORs(95% CI)of circulating metabolic measures for hypertriglyceridemia were assessed using logistic regression.Pooled results of metabolites with same direction of association in both cohorts were combined using inverse variance-weighted fixed-effect meta-analysis.Difference of identified metabolites in patients with and without hypertriglyceridemia were also obtained in the context of LDL-C.Results:We observed that elevated alanine,asparagine,leucine and valine were consistently associated with increased hypertriglyceridemia in both cohorts.In fixed effect pooled analysis,the OR(95%CI)of per SD increased was 1.71(1.32-2.20)for alanine,1.62(1.20-2.19)for asparagine,1.64(1.22-2.20)for leucine and 1.62(1.22-2.13)for valine(all P value ranged from 0.0018 to <.0001);adjusting for C-peptide attenuated effect sizes of Ala,Leu and Val for hypertriglyceridemia.The difference were robust in groups with well-or bad-controlled LDL-C.Conclusion:Alanine,asparagine,leucine and valine were positively associated with increased residual risk of hypertriglyceridemia in diabetic patients with statins treatment.