Mediation Role Of 8-OHdG In The Relationship Between Heavy Metal Exposure And Diabetes Mellitus In Community-dwelling Older Adults

Objective:1.To study the relationship between exposure to different heavy metals in urine and diabetes in community-dwelling elderly population.2.To analyze the relationship between the combined exposure levels of multiple heavy metals and the risk of diabetes mellitus in the study subjects.3 To explore the mediating effect of 8-OHd G in the relationship between urinary heavy metals and diabetes mellitus.Methods:1.In this study,a cross-sectional study method was used to recruit permanent residents of the community as study subjects in two communities in a city in northern China from October 2020 to June 2021.Health examinations and biological samples were collected by professional medical staffs,and information on the basic characteristics,personal disease history,lifestyle and occupational history of the study subjects was collected through face-to-face questionnaire survey.2.Agilent 7900 inductively coupled plasma mass spectrometer（ICP-MS）was used to detect urinary heavy metals.Automatic biochemical analyzer was used to detect fasting blood glucose,total cholesterol,high-density lipoprotein cholesterol and low-density lipoprotein cholesterol.Sarcosine oxidase method was used to detect urinary creatinine,and enzyme-linked immunosorbent assay was used to measure the level of urinary 8-OHd G.3.Epidata 3.1 software was used for double entry of data,SPSS 23.0 was used for statistical analysis.The variability of variables between two subgroups were compared by Chi-square test and Mann-Whitney U test.Binary logistic regression was conducted to analyze the relationship between single heavy metals and diabetes.Correlation analysis was performed by R4.0.5.Correlation heat map was drawn to present the relationship between each heavy metal.The Lasso regression model was used to select the heavy metal variables that fit the model,and the selected variables were analyzed in a multi-metal model,using a Bayesian kernel function regression model to analyze the relationship between the combined effect of multiple metals and diabetes.The"RMediation"package was conducted to explore the mediating role of 8-OHd G in the relationship between urinary heavy metals and diabetes.Results:1.A total of 761 study subjects were included in this study,including 270 in the diabetic group and 491 in the control group.The diabetic group had higher education level（c²=6.384,P=0.041）and a higher composition ratio of smokers（c²=11.524,P=0.001）compared to the control group.In addition,waist circumference（Z=-2.023,P=0.043）,fasting blood glucose（Z=-12.658,P<0.001）,total cholesterol（Z=-2.133,P=0.033）,and low-density lipoprotein（Z=-2.038,P=0.042）were higher in the diabetic group.The detection rates of all 13 heavy metals included in the study were higher than 80%.There are higher concentrations of magnesium,boron,rubidium,and strontium and lower concentrations of cobalt,cadmium,and chromium in the urine of the study subjects.The distribution of 8-OHd G in the diabetic group[M(P₂₅,P₇₅)]was[2.55（2.26,2.97）]ng/m L,which was higher than the level of 8-OHd G in the control group[2.46（2.10,2.90）]ng/m L（Z=-3.282,P=0.001）.2.Binary logistic regression analysis of the relationship between heavy metals and diabetes revealed that heavy metals cadmium（OR=1.330,95%CI:1.007-1.756）,lead（OR=1.987,95%CI:1.314-1.3.）,chromium（OR=1.987,95%CI:1.314-1.3.）and vanadium（OR=1.537,95%CI:0.298-0.966）were the influencing factors of developing diabetes after adjusted for education,smoking,waist circumference,total cholesterol,and low-density lipoprotein cholesterol.3.The analysis of the relationship between the combined effects of heavy metals and diabetes showed that the combined effects of three heavy metals,lead,cadmium and chromium could increase the risk of diabetes.The combined effects of lead and cadmium may increase the risk of diabetes.4.Regression analysis of the relationship between heavy metals,8-OHd G and diabetes showed that urinary cadmium and urinary lead exposure may increase 8-OHd G levels.After adjusted for other possible confounding factors,it was found that elevated 8-OHd G levels may increase the risk of developing diabetes.5.Mediating effect analysis showed that 8-OHd G had a mediating effect in the relationship between cadmium and diabetes and lead and diabetes,and both were partial mediators.Urinary cadmium and urinary lead may affect the risk of diabetes through elevated 8-OHd G levels.Conclusions:1.Exposure to cadmium,lead,chromium and vanadium in the elderly population’urine is associated with diabetes,and cadmium,lead and chromium may play the risk factors’role for diabetes and vanadium could be a possible protective factor for diabetes.2.The combined effects of three heavy metals,lead,cadmium and chromium probably increase the risk of diabetes in the elderly population,and lead and cadmium may increase the risk of diabetes in the elderly population by producing synergistic effects.3.Cadmium and lead may increase the risk of diabetes in the elderly population through oxidative DNA damage.