Associations Of Plasma Essential Trace Elements With Metabolic Syndrome

The metabolic syndrome(Met S)is a constellation of metabolic abnormalities including abdominal obesity,dyslipidemia,hypertension and hyperglycemia.Past decades had seen an increased incidence and prevalence of Met S.A huge body of evidence had indicated that Met S significantly increased risks of incident cardiovascular disease(CVD)and diabetes as well as all-cause mortality.Hence,identifying and controlling the risk factors of Met S play important roles in reducing the burdens of CVD and diabetes,and improving human health.As indispensable nutrients involved in body constitution,metabolism,and physiological function,adequate levels of essential trace elements play critical roles in metabolism homeostasis,whereas excess levels are associated with perturbations in glucose and lipid metabolism,and reduced cardiovascular function.Previous studies had provided evidence of associations between essential trace elements and perturbations in glucose and lipid metabolism,and risk of Met S,nonetheless,results remain inconsistent.Moreover,considering the ubiquitous exposure and comment sources of these trace elements,it is reasonable to investigate the association of concurrent exposure of essential trace elements with risk of Met S.However,previous studies typically examined the association of singular element with Met S,and much remains to be learned about the overall effect of essential trace elements on risk of Met S.A growing body of evidence had indicated that inflammation play a crucial part in the pathogenesis of Met S.Nonetheless,little was known about the role of C-reactive protein(CRP),the biomarker of inflammation,in the associations of essential trace elements with Met S.Hence,we aimed to investigate the associations of essential trace elements with risk of Met S in this study.The overall effect of these elements on risk of Met S,and potential mediation effect of CRP in the associations of essential trace elements with Met S prevalence,were further examined.The following three sections were included in our research.Section 1: Associations of Plasma Essential Trace Elements with Metabolic SyndromeObjective: To determine the association between the plasma essential trace elements levels and the risk of Met S as well as its components.Methods: A matched case-control study was conducted in Nanshan district of Shenzhen where the residents had medical examinations from 2018 to 2019 at community health service centers.Met S cases and healthy controls were matched 1:1 according to gender and age(± 2 years).A total of 2326 individuals were included in the study,including1163 Met S cases and 1163 control subjects.The unified semi-structured questionnaires were used by trained researchers to collect basic information of the subjects.Fasting blood samples were collected after the subjects fasting for 10 hours.The levels of plasma essential trace elements(Cu,Zn,Se,Cr,Co and Mo)were quantitatively detected by inductively coupled plasma mass spectrometry.By calculating odds ratio(OR)and 95% confidence intervals(CI)in Logistic regression model to evaluate the associations of plasma essential trace elements with Met S and its components.What’s more,the restricted cubic spline regression model was used to investigate the non-linear relationship between plasma essential trace elements levels and the risk of Met S.Results: Median of plasma selenium level in Met S group was significantly higher than control group,while plasma chromium,cobalt,and molybdenum levels were significantly lower than control group.After adjusting for confounding factors,we found that,compared with the subjects with plasma selenium,chromium,cobalt,and molybdenum levels in the first quartile,the OR(95% CI)of Met S in the fourth quartile were 1.44(1.08-1.93),0.57(0.43-0.76),0.70(0.53-0.92),0.53(0.40-0.71),and per SD increment of log-transformed plasma selenium,chromium,cobalt,and molybdenum were associated with 12%(OR: 1.12,95% CI: 1.01-1.25)higher risk and 21%(OR: 0.79,95% CI: 0.72-0.88),9%(OR: 0.91,95%CI: 0.82-1.00),19%(OR: 0.81,95% CI: 0.74-0.90)lower risk of Met S.The results of the restricted cubic spline regression model showed that plasma selenium and cobalt levels were linearly correlated with the risk Met S,while plasma chromium and molybdenum levels were non-linearly correlated with the risk of Met S.Plasma copper was positively associated with central obesity and hypertension;plasma zinc was positively associated with hypertriglyceridemia;plasma selenium was positively associated with hypertriglyceridemia and hyperglycemia,and plasma selenium was negatively associated with low high-density lipoprotein cholesterol(HDL-C);plasma chromium was negatively associated with central obesity,low HDL-C and hyperglycemia;plasma cobalt was negatively associated with central obesity and hypertriglyceridemia;plasma Molybdenum was negatively associated with central obesity,hypertriglyceridemia and hyperglycemia.Conclusion: Higher plasma selenium and lower plasma chromium,cobalt,molybdenum levels were positively associated with higher risk of Met S.Section 2: The Joint Effect of Plasma Essential Trace Elements for Metabolic SyndromeObjective: To comprehensively evaluate the joint effects of plasma essential trace elements for the risk of Met S.Methods: Participant recruitment and case-control matching methods were described in section 1.Plasma essential trace elements in relation to Met S were screened by elastic net(ENET)regression model,and regression coefficients of each essential trace elements in the model were calculated with 10-fold cross-validation method.Plasma essential trace elements environmental risk score(ERS)was calculated by weighted addition method.The relationship of plasma essential trace elements ERS with the risk of Met S and its components were analyzed by Logistic regression model.The improvement effect of plasma essential trace elements ERS beyond traditional risk factors on Met S prediction model was evaluated by plotting and calculating the area under receiver operating characteristic curve(ROC),integrated discrimination improvement(IDI)and net reclassification improvement(NRI).Results: Four plasma essential trace elements(Se,Cr,Co and Mo)associated with Met S were included after screening by the ENET.After adjusting for multiple confounders,the OR(95% CI)for Met S were 1.00(reference),0.61(0.47-0.79)、0.59(0.45-0.77)and0.46(0.35-0.62)across quartiles of plasma essential trace elements ERS,respectively,and per SD increment of plasma essential trace elements ERS was associated with 21%(OR:0.79,95% CI: 0.71-0.88)lower risk of Met S.With the addition of plasma essential trace elements ERS to the conventional model for Met S,the area under the ROC significantly increased from 0.71 to 0.74(IDI: 2.6%,P < 0.001;NRI: 6.8%,P < 0.001).Conclusion: The results showed that plasma essential trace elements ERS screened and constructed based on ENET was inversely correlated with Met S risk.Adding plasma essential trace elements ERS to the conventional model significantly improved the risk prediction model for Met S.Section 3: Mediating Effects of C Reactive Protein on the Relationship between Plasma Essential Trace Elements and Metabolic SyndromeObjective: To explore the mediating role of serum CRP in the relationship between plasma essential trace elements and Met S.Methods: Participant recruitment and case-control matching methods were described in section 1.Serum CRP levels were detected by enzyme-linked immunosorbent assay.Logistic regression model was used to analyze the association of CRP level with the risk of Met S and its components.The relationships between serum CRP and plasma essential trace elements were analyzed by generalized linear regression model.The “mediation” R software package was used to analyze the mediating effects of CRP on the relationship between plasma essential trace elements and the risk of Met S.Results: Compared with the subjects with CRP in the first quartile,the OR(95% CI)for Met S in the third and fourth quartile were 1.64(1.23-2.17)and 2.01(1.52-2.65)after adjusting multiple confouders,and per SD increased of log-transformed CRP was associated with 25%(OR: 1.25,95% CI: 1.13-1.37)higher risk of Met S.For the components of Met S,per SD increment of log-transformed CRP were associated with 63%(OR: 1.63,95% CI:1.47-1.80),24%(OR: 1.24,95% CI: 1.14-1.37),19%(OR: 1.19,95% CI: 1.08-1.31),21%(OR: 1.21,95% CI: 1.10-1.34)and 25%(OR: 1.25,95% CI: 1.13-1.38)higher risk of central obesity,hypertriglyceridemia,low HDL-C,hypertension and hyperglycemia,respectively.CRP was correlated with plasma copper positively and cobalt negatively.The mediation analysis suggested that CRP mediated the inverse association between plasma cobalt levels and the risk of Met S,with a mediation proportion of 15.0%.(P = 0.016).Conclusion: Higher serum CRP levels were positively associated with higher risk of Met S and its component.CRP was correlated with plasma copper positively and cobalt negatively.CRP mediated the inverse association between plasma cobalt levels and the risk of Met S,with a mediation proportion of 15.0%.