Association between blood dioxin level and health outcomes in an endemic area of exposure in southern Taiwan

Abstract

Background: Dioxin is an industrial pollutant related to various diseases It can activate the AhR and then suppress the function of PPAR γ which may progressively lower the translation of GLUT4 and then cause metabolic effect like insulin resistance and hyperglycemia However epidemiology studies on its effects on metabolic disease or kidney disease found inconsistent results This study in an area in Taiwan where the residents were exposed to dioxin released from environmental pollution has three parts: 1 Studies on sex differences in metabolic disorders found inconsistent results from and did not evaluate the differences in effects according to the age at starting exposure Therefore we conducted a study to evaluate the associations between dioxin exposure and metabolic syndrome (MetS) and to determine whether the associations are different between men and women and whether the associations depend on the age at starting exposure 2 Previous studies of diabetes mellitus (DM) did not have consistent findings on the effects of dioxin between the two sexes Therefore we conducted a study to assess the effects according to sex and years of residency and to identify related factors 3 Regarding the association between dioxin and chronic kidney disease (CKD) there were only animal studies on mechanisms and no epidemiology studies Therefore we conducted a study to evaluate the association between dioxin and CKD and identify the related factors Methods: We recruited participants from an area where residents were exposed to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) released from a factory 1 We defined serum PCDD/Fs levels ? 20 pg WHO98-TEQDF/g lipid as high dioxin levels MetS was defined as meeting three of the following: fasting glucose ? 100 mg/dL or under treatment for diabetes waist circumference ? 90 cm in men or ? 80 cm in women triglycerides ? 150 mg/dL or under treatment for elevated triglycerides high-density lipoprotein <40 mg/dL in men or <50 mg/dL in women and blood pressures ? 130/85 mmHg or under treatment for hypertension 2 Using 20 and 64 pg WHO98-TEQDF/g lipid as the cut-offs we categorized participants into three groups according to the level of PCDD/Fs in the serum We defined DM as a fasting plasma glucose level > 126 mg/dl or an existing diagnosis 3 We defined a “high dioxin level” as PCDD/Fs ? 20 pg WHO98-TEQDF/g lipid in the serum and defined CKD as having an estimated glomerular filtration rate (e-GFR) ? 60 mL/min/1 73m2 or a diagnosis of CKD by a physician The renal function was assessed between 2005 and 2010 and we excluded those who had had kidney diseases before the study started Comparisons between patients of CKD and those who did not have CKD were made to identify the risk factors for CKD Results: 1 Of the 2898 participants 1427 had high dioxin levels and 156 had CKD In the univariate analyses CKD was associated with high dioxin levels age gender metabolic syndrome diabetes mellitus hypertension and high insulin and uric acid levels After adjusting for other factors we found high dioxin levels (AOR = 1 76 95% CI: 1 04-2 99) female gender (AOR = 1 74 95%CI: 1 20-2 53) hypertension (AOR = 1 68 95%CI: 1 17-2 42) high insulin levels (AOR = 2 14 95% CI: 1 26-3 61) high uric acid levels (AOR = 4 25 95% CI: 2 92-6 20) and older age (AOR = 4 66 95% CI: 1 87-11 62 for 40-64 year and AOR = 26 66 95% CI: 10 51-67 62 for age ? 65 year) were independent predictors of CKD 2 Of the 2758 participants 785 patients of MetS were identified and we observed positive associations between a high dioxin level and MetS After adjusting for sex age and age at starting exposure we found a high dioxin level was an independent predictor for MetS (AOR = 1 38 95% CI: 1 11-1 72) Male (AOR = 1 22 95% CI: 1 02-1 46) old age (AOR for 40-64 years old = 2 61 95% CI: 2 04-3 34; AOR for ? 65 years old = 3 13 95% CI: 2 15-4 56) and exposure age> 12 years (AOR = 1 51 95% CI: 1 15-1 99) are independent predictor too When we stratified the participants by sex we found that a high dioxin remained an independent predictor of MetS in men but not in women regardless of the age at starting exposure 3 Of the 2898 participants 425 patients of DM were identified and we observed positive associations between dioxin and DM After adjusting for age and BMI we found a high serum dioxin level was an independent risk factor for DM (associated with 20-64 pg WHO98-TEQDF/g lipid AOR = 2 1 95% CI: 1 5-2 9; AOR for > 64 pg WHO98-TEQDF/g lipid = 3 2 95% CI: 2 1-4 8) The findings are compatible with those in previous studies of PCDD/Fs When we stratified the participants by gender the serum dioxin level remained an independent risk factor for DM in both men and women Conclusion: In conclusion we found that exposure to dioxin is a risk factor for DM independent of age and BMI in both men and women It is also a predictor of MetS in men independent of age and age at starting exposure but not in women In our study but the gender differance still need further study to clarify Our study also observed an association between high blood dioxin levels and CKD Whereas the mechanisms by which dioxin causes renal toxicity are still unclear and need further research results of this study suggested that there might be pathways other than the association between dioxin and hypertension or DM As dioxin becomes an emerging environmental health hazard globally the kidney function of exposed populations should be monitored and screening programs for identifying DM and MetS in its early stage and intervention programs for prevention and control of DM and MetS should be considered in endemic areas of exposure

Date of Award	2018 Feb 23
Original language	English
Supervisor	How-Ran Guo (Supervisor)