Associatons Of Multiple Metals Exposure With Diabetes Risk And Their Influencing Factors

Part One: Associations of multiple metals exposure with diabetes riskObjective: This study aimed to assess the associations of multiple metals exposure and diabetes risk.Methods: Participants involved in this study were from the baseline-population(n=9411,adults aged of ≥ 60 years)of the Shenzhen Aging Related Disorder Cohort.They answered the questionnaires and took part in the physical examinations.Among them,7401 individuals were finally included in this study,after excluding individuals with missing data on educational level(n=90),active smoking(n=48),passive smoking(n=31),alcohol consumption(n=17),physical activity(n=31),body mass index(n=103),hypertension(n=12),diabetes(n=33),estimated glomerular filtration rate(n=21),blood lipids(n=2)and urinary metals levels(n=1622).Urinary concentrations of 24 metals were measured by using inductively coupled plasma mass spectrometry,including lithium,beryllium,aluminum,titanium,vanadium,chromium,manganese,iron,cobalt,nickel,copper,zinc,arsenic,selenium,rubidium,strontium,molybdenum,cadmium,indium,tin,antimony,barium,thallium and lead.Urinary creatinine concentration was measured by a fully-automated chemistry analyzer.We assessed the association between urinary concentration of each metal element and diabetes risk by non-conditional Logistic regression analysis.The Elastic net(ENET)was used to perform variable selection from the 275 predicators(including 22 main effects,22 squared terms and 231 pairwise interaction of urinary metals)for diabetes risk.Environmental risk score(ERS)was proposed as a summary measure to assess the risk of exposure to multiple metals by using beta coefficients adopted from ENET.We further assessed the association of ERS with diabetes risk by Logitic regression analysis.Results: Logistic regression analysis showed that among the elderly,each 1-unit increase in urinary detected concentration(log-transformed)of chromium,manganese,cobalt,nickel,copper,zinc,selenium or antimony was correspondingly associated with a 51%(95%CI: 1.29,1.77),13%(95%CI: 1.01,1.26),17%(95%CI: 1.05,1.30),57%(95%CI:1.36,1.82),35%(95%CI: 1.19,1.53),706%(95%CI: 6.49,10.01),52%(95%CI: 1.26,1.84)or 24%(95%CI: 1.14,1.34)increased risk of diabetes.Each 1-unit increase in urinary detected concentration(log-transformed)of vanadium or strontium corresponded to a 26%(95%CI: 0.63,0.87)or 18%(95%CI: 0.72,0.94)reduction in the risk of diabetes.We found the a positive association between ERS and increased diabetes risk [β=3.05,95%CI(2.83,3.28)],after adjusted for age,gender,educational level,active smoking,passive smoking,alcohol consumption,physical activity,body mass index,estimated glomerular filtration rate,low density lipoprotein,high density lipoprotein,triglyceride,total cholesterol,hypertension and urinary creatinine level.Conclusions: Exposure to multiple metals was positively related to diabetes risk in the participants aged ≥ 60 years.Urinary concentration of chromium,nickel,copper,zinc or antimony was positively associated with the risk of diabetes,while urinary concentration of vanadium or strontium was negatively associated with diabetes risk.Part two: Associations of metals exposure with diabetes risk: the Multiple Mediation EffectsObjective: This study aimed to assess the potential mediating effects of inflammatory indicators or mitochondrial DNA copy number on the associations of multiple metals exposure with diabetes risk.Methods: Based on data from the baseline-population(n=9411,adults aged of ≥ 60 years)of the Shenzhen Aging Related Disorder Cohort,7007 individuals were finally included in this study,after excluding individuals with missing data on educational level(n=90),active smoking(n=48),passive smoking(n=31),alcohol consumption(n=17),physical activity(n=31),body mass index(n=103),hypertension(n=12),diabetes(n=33),estimated glomerular filtration rate(n=21),blood lipids(n=2),urinary metals levels(n=1622)and peripheral blood mitochondrial DNA copy number(n=394).We performed multiple mediation analysis to estimate potential factors(including white blood cell,platelet count,neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune inflammation indicators,peripheral blood mitochondrial DNA copy number)affecting the associations between exposure to multiple metals and diabetes risk.Results: The mediation analysis revealed that white blood cell,platelet count mediated the relationship between multiple metals exposure and diabetes risk;white blood cell was a mediator of the relationship between urinary concentration of vanadium,copper,zinc or antimony and diabetes risk;peripheral blood mitochondrial DNA mediated the relationship of urinary concentration of chromium or nickel with diabetes risk.Conclusions: White blood cell or peripheral blood mitochondrial DNA copy number could partially mediate the relationship of urinary concentration of vanadium,copper,zinc,antimony,chromium or nickel with diabetes risk.