The Association Of Urinary Perchlorate,nitrate And Thiocyanate With Metrcis Of Glucose And Lipid Metabolism

Objective:To investigate the association of urinary thiocyanate,nitrate and thiocyanate with glucose and lipid metabolism metrics.Method:Residents,whose basic information were collected with questionnaire,had participated in physical examinations in four community health service centers in Nanshan District,Shenzhen,and were included in the current study.Researchers conducted physical examinations for surveyed subjects,of which the blood and urine specimens were collected for further laboratory tests.Urinary perchlorate,nitrate and thiocyanate levels were measured with ultra high performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）.Multivariate linear regression model and generalized additive model were investigate the association of urinary perchlorate,nitrate and thiocyanate with glucose and lipid metabolism metrics,including fasting plasma glucose（FPG）,triglyceride（TG）,fasting plasma insulin（FPI）,Hemoglobin A1c（HbA1c）,total cholesterol（TC）,homeostasis model assessment of insulin resistance（HOMA-IR）,low-density lipoprotein cholesterol（LDL-C）.Weighted quantile sum（WQS）regression was conducted to investigate the association between co-exposure of perchlorate,nitrate and thiocyanate and glucose and lipid metabolism metrics.The multivariate linear regression model was repeated to test the robustness of our results,after outliers(defined as<1^st or>99^th percentile)of urinary thiocyanate were excluded.Results:A total of 2234 residents,including 756 men and 1478 women,with a mean age of48.1 years were included in this study.The medians（interquartile ranges）of urinary creatine-adjusted perchlorate,nitrate and thiocyanate were 5.75（3.68-9.86）μg/g Cr,80.73（50.66-139.86）mg/g Cr and 280.74（168.81-497.19）μg/g Cr,respectively.As revealed in multivariate linear regression model,compared with the lowest perchlorate quartile（Q1）,the regression coefficient（β）±standard error（SE）of TG in the highest quartile（Q4）was 0.066±0.032（P<0.05）,after adjusting for confounders,such as age,sex,BMI and exercise habits.Nevertheless,urinary nitrate was inversely associated with TG in a linear manner（β±SE:-0.087±0.033,P<0.01,P-trend=0.005）.Additionally,higher urinary perchlorate and thiocyanate were associated with increased HbA1c,HOMA-IR,TG,TC and LDL-C,after adjusting for confounders in generalized additive model.However,FPG,FPI,HbA1c,HOMA-IR,TG,TC and LDL-C decreased,following with the increment of urinary nitrate.Weighted quantile sum（WQS）regression revealed a significant positive linear association between WQS index,which represented the co-exposure of three anions,and triglyceride（WQSβ=0.107,95%CI:0.032-0.182,P<0.01）.Moreover,the WQS index was primarily attributed to perchlorate and thiocyanate,which account for 52%and 41%of the index,respectively.Associations of urinary perchlorate,nitrate and thiocyanate with glucose and lipid metabolism metrics persisted in sensitivity analysis.Conclusions:Higher urinary perchlorate was associated with an increased TG level.In addition,we observed an inverse,linear association of urinary nitrate with TG.Morever,co-exposure of perchlorate,nitrate and thiocyanate was positively associated with TG in a linear manner.Nevertheless,further prospective studies are warranted to replicate and verify our findings,and the underlying molecular mechanisms need further investigation.