Plasma Metals And Cardiovascular Disease Among Subjects With Type 2 Diabetes

Objective: Metals exposure from natural environment and pollution have been linked to cardiovascular disease(CVD).However,whether associations existing between plasma multiple metals and incident cardiovascular disease in type 2 diabetes cases is unknown.Therefore,we conducted a prospective cohort study to investigate whether plasma levels of metals are associated with incident CVD risk in individuals with type 2 diabetes.Methods: In a prospective study of 3,897 type 2 diabetes embedded in the DongfengTongji cohort,we measured baseline plasma concentrations of 23 metals by inductively coupled plasma mass spectrometry(ICP-MS).The continuous variables of normal distribution are expressed as mean ± SD,the continuous variables of non-normal distribution are expressed as median(P25,P75),and categorical variables are expressed as n(%).The outcome of the present study was incident CVD among subjects with type 2 diabetes,including incident coronary heart disease(CHD)and stroke.Baseline characteristics were compared using t-tests or Mann-Whitney U tests for continuous variables,and chi-square tests for categorical variables.The associations between plasma metal concentrations and CVD risk among type 2 diabetes were investigated with Cox proportional hazards models and Restricted cubic spline(RCS).In addition,we evaluated the combined and interactive effects of plasma metals on cardiovascular disease risk among subjects with type 2 diabetes.Results: During an average of 6.2 years' follow-up,1,114 participants developed CVD.In the single-metal models adjusting for established cardiovascular risk factors,plasma zinc and selenium levels were negatively and strontium were positively associated with incident CVD risk among type 2 diabetes.Comparing with the extreme quartiles of metal,the multivariable adjusted HRs(95% CI)of CVD were 0.76(0.64-0.90,P trend= 0.003)for zinc,0.79(0.66-0.93;P trend = 0.002)for selenium,and 1.41(1.18-1.68;P trend < 0.001)for strontium.Similar results were obtained in the multiple-metal model,the HRs(95% CIs)for zinc,selenium,and strontium comparing extreme quartiles were 0.78(95% CI: 0.65-0.93;P trend = 0.011),0.76(95% CI: 0.64-0.91;P trend = 0.001),and 1.51(95% CI: 1.26-1.81;P trend < 0.001),respectively.In the joint association analyses of two metals,combined low zinc and high strontium were associated with an increased risk of incident CVD among type 2 diabetes(HR = 1.38;95% CI:1.16-1.64;P < 0.001)compared with combined high zinc and low strontium values.Similarly,combined low selenium and high strontium increased 52%(95% CI: 1.27-1.83;P < 0.001)risk of incident CVD among type 2 diabetes compared with combined high selenium and low strontium.In addition,individuals with high plasma levels of zinc and selenium had significantly lower risk of incident CVD among type 2 diabetes than those with low levels(HR = 0.77,95% CI: 0.65-0.91;P < 0.001).In the stratification association analyses,the association between plasma zinc,selenium and incident CVD among type 2 diabetes was more pronounced in males and individuals who were younger than 65 years of age,obesity,nonsmokers,and nondrinkers.However,the association between plasma strontium and incident CVD risk among type 2 diabetes was stronger in females and individuals who were younger than 65 years of age,obesity,smokers,and nondrinkers.Conclusions: The present study suggested that plasma levels of zinc and selenium had an inverse association with incident CVD risk among type 2 diabetes,while strontium had a positive correlation.Plasma zinc and selenium combinedly decreased incident CVD risk among type 2 diabetes.