Study On The Relationship Between Serum Branched Chain Amino Acids And Oxidative Stress, Type 2 Diabetes And Cardiovascular Disease Risk

PartⅠAssociation between Branched-chain amino acids,oxidative stress and newly diagnosed diabetes mellitus in Chinese populationObjective:Branched chain amino acids(BCAAs)are the important nutrition metabolic signaling which are widely used as antioxidants in patients with liver and kidney dysfunction and delay the progress of the disease.However,BCAAs are strongly correlated with insulin resistance(IR)and are predictors of diabetes.Mechanism remains unclear.This study aimed to evaluate the relationship between BCAAs,oxidative stress,and type 2 diabetes mellitus incident risk in middle-aged and elderly Chinese population.Methods:Anthropometric and biochemical examinations were performed in 816 individuals from the general population,aged 40-79 years,who participated in the Huaian Diabetes Prevention Program.All participants were divided into three groups(normal glucose metabolism(NGM),prediabetes,and newly diagnosed diabetes mellitus(NDM)).Serum BCAAs(L-leucine,L-isoleucine and L-valine)concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method.Oxidative stress was evaluated by Malondialdehyde(MDA)as an index of lipid peroxidation and the Superoxide Dismutase(SOD)activity.Results:Subjects in NDM group were more likely to be higher MDA level and lower SOD level than Subjects in NGM and prediabetes groups.After adjusting for the traditional risk factors of MDA,L-Val was also found to be an independent predictor of MDA in different glucose metabolism groups.After adjusting for T2DM risk factors,high L-Val levels were significantly associated with higher BMI,WC,FPG,more unfavorable lipid profile(increased LnTG and decreased HDL-C).Moreover,after adjusting for similar factors,L-Val were independently associated with NDM(OR 1.06,95%CI 1.01-1.07;P=0.005).Furthermore,the odds ratios for NDM among participants with high L-Val levels and high MDA levels showed a 2.01-fold(95%CI 1.11-3.59;P=0.034)increase compared to participants with low L-Val levels and MDA levels after adjusting for confound factors.Conclusions:High L-Val levels with oxidative stress could be a significant risk factor for increased T2DM incidence risk;and that oxidative stress may contribute to IR and an increased NDM in subjects with high L-Val levels.Intervention studies are needed to investigate whether a strategy to reduce L-Val levels can improve oxidative stress and reduce the risk of T2DM incident.Part ⅡThe Relationship between Branched-Chain Amino Acids,Metabolic Syndrome and Cardiovascular Risk Profile in a Chinese Population:a Cross-Sectional StudyObjective:Branched-chain amino acids(BCAAs)are strongly correlated with visceral obesity and insulin resistance(IR)and are predictors of diabetes.However,it is not clear whether BCAAs could be regarded as independent risk factors for cardiovascular disease(CVD).This study aimed to evaluate the relationship between BCAAs,metabolic syndrome(MS),and other cardiovascular(CV)risk factors in middle-aged and elderly Chinese population at high risk for the development of CVD.Methods:A total of 1302 subjects aged from 40 to 79 years old were enrolled from the Huai’an Diabetes Prevention Program.Anthropometric and biochemical examinations were performed and stratification was done on the basis of BCAAs quartiles.MS was defined according to the Adult Treatment Panel Ⅲ criteria.Serum BCAAs(leucine,isoleucine and valine)concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method.Results:BCAAs levels were positively correlated with MS,its components and CV risk profile.After adjusting for several traditional risk factors,the odds ratio(OR)for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile.Multivariate logistic regression analysis revealed that BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components(OR 1.03,95%CI 1.00-1.04;P<0.0001),Additionally,the OR for high CV risk were 3.20 fold(95%CI 1.83-5.61;P<0.0001)in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS.Conclusions:Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population.The development of CVD in MS patients with high level BCAAs is accelerated.Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk.