Associations Between Multiple-Metals Exposure And Fasting Blood Glucose In The Manganese-Exposed Workers Healthy Cohort And The Fangchenggang Area Male Health And Examination Survey Cohort

Objective:FBG（Fasting Blood Glucose）is one of the important indicators of diabetes diagnosis and monitoring.At present,the level of fasting blood glucose and the prevalence of diabetes are gradually increasing in the world.Many studies had reported that the exposure of metal elements is related to the blood glucose level and the occurrence and development of diabetes.But the relationship between multiple metal compound exposure and fasting blood glucose level is relatively scarce.In this study,the plasma of the MEWHC（Manganese-exposed Workers Healthy Cohort）and the serum of the FAMHES（Fangchenggang Area Male Health and Examination Survey Cohort）were selected as biomarkers of internal exposure of 22 metals to explore the relationship between metals and fasting blood glucose in multiple-metals exposure.Methods:In this study,the follow-up subjects of the Manganese-exposed Workers Healthy Cohort in 2017 were selected as the occupational population,and the baseline population of the Fangchenggang Area Male Health and Examination Survey cohort in 2009 was selected as the natural population.According to the inclusion exclusion criteria,769 occupational workers and 1927men were selected as the occupational population and the natural population respectively.We divided the manganese exposed workers into a control group or a low,medium,or high exposure group based on their occupations and the corresponding concentrations of airborne manganese.ICP-MS（Inductively Coupled Plasma Mass Spectrometer）was used to detect the concentrations of 22metals in the plasma of occupational workers and the serum of men.All metal concentrations in the data analysis were log-10 transformed.The elastic network regression was used to screen out the metals which were positive associated with fasting blood glucose level,then build the multiple-metals exposure model.The relationship between metals and fasting blood glucose level and the dose-response relationship were analyzed by multiple linear regression model and RCS（Restricted Cubic Spline）.Finally,the metals with dose-response relationship were stratified analyzed according to the possible influencing factors.Results:1.The highest concentration of plasma metal in the Manganese-exposed Workers Healthy Cohort was calcium,followed by magnesium,zinc and iron.The distribution of vanadium,calcium,aluminum,molybdenum,lead,rubidium,arsenic,iron,selenium between the control group and the low,medium and high exposure groups were statistically different.In the linear regression model of single plasma metal and fasting blood glucose,adjusted for gender,age,BMI,groups,seniority,education,married status,smoking status and alcoholic intake status,there was significant correlation between plasma magnesium and fasting blood glucose after multiple FDR adjustments(P for trend<0.05 or P _continuous<0.05).In the multiple-metals model of 13 metals（barium,cadmium,chromium,cobalt,magnesium,molybdenum,arsenic,strontium,titanium,antimony,iron,copper,selenium）were selected by elastic regression.The results of multiple linear regression and restricted cubic spline analysis showed that there was a linear negative correlation between plasma magnesium and fasting blood glucose（P for overall=0.0016,P for nonlinearity=0.8101）.The results of stratified analysis showed that the relationship between plasma magnesium and fasting blood glucose was more significant in the control group,high exposure group,people under 30 years of age or over 40 years of age,seniority of 10-20 years or over 30 years,BMI in the range of 18.5-23.9 kg/m²,current smokers and never smokers,never drinkers.There was no interaction between plasma magnesium and these factors（P for interaction>0.05）.2.The highest content of metal elements in the serum of the Fangchenggang Area Male Health and Examination Survey cohort was calcium,followed by magnesium,zinc,iron and copper.In the linear regression model of serum single metal and fasting blood glucose,after adjusting for age,BMI,education,married status,smoking status and alcoholic intake status,there was a significant correlation between serum lead,rubidium,strontium,copper,selenium,tin and fasting blood glucose(P for trend<0.05 or P _continuous<0.05).In the multiple-metals model of 15 metals（calcium,cadmium,cobalt,aluminum,magnesium,molybdenum,nickel,lead,rubidium,strontium,titanium,iron,copper,selenium and tin）were screened out by elastic network.The results of multiple linear regression and restricted cubic spline analysis showed that serum magnesium,lead,rubidium,selenium,tin was associated with fasting blood glucose（P for overall<0.05）.And there were negative linear relationships between magnesium,lead,rubidium and fasting blood glucose（magnesium:P for nonlinearity=0.4015;lead:P for nonlinearity=0.3107）.Serum rubidium and selenium was positive linear associated with fasting blood glucose（rubidium:P for nonlinearity=0.9679;selenium:P for nonlinearity=0.2850）.And there was a U-shaped dose-response relationship between serum tin and fasting blood glucose（P for nonlinearity=0.0022）.In the stratified analysis of serum magnesium,lead,rubidium,selenium and tin,there was no interaction between metal and age,BMI,smoking and drinking on fasting blood glucose（P for interaction>0.05）.3.In the comparison between the occupational population and the natural population,the group of the Manganese-exposed Workers Healthy Cohort were older,less educated,more married or cohabiting,and fewer people have the habit of smoking and drinking.The average level of fasting blood glucose was higher in the Fangchenggang Area Male Health and Examination Survey cohort.After adjusting for gender,age,BMI,education,married status,smoking status and alcoholic intake status,the occupational group had higher levels of cadmium,chromium,molybdenum,nickel,lead,titanium,zinc and lower levels of barium,vanadium,calcium,magnesium,manganese,rubidium,arsenic,strontium,iron,copper,selenium,tin.Conclusions:This study found that there was a negative linear relationship between plasma magnesium and fasting blood glucose in the workers of Manganese-exposed Workers Healthy Cohort.And there were a negative linear relationship between serum magnesium,lead and fasting blood glucose,a positive linear relationship between serum rubidium,selenium,and fasting blood glucose,and a U-shaped dose-response relationship between serum tin and fasting blood glucose in the men of the Fangchenggang Area Male Health and Examination Survey cohort.