Jung Wei Chang

Simultaneous exposure of non-diabetics to high levels of dioxins and mercury increases their risk of insulin resistance

Insulin resistance and the defective function of pancreatic β-cells can occur several years before the development of type 2 diabetes. It is necessary to investigate and clarify the integrated effects of moderate-to-high exposure to dioxins and mercury on the pancreatic endocrine function. This cross-sectional study investigated 1449 non-diabetic residents near a deserted pentachlorophenol and chloralkali factory. Metabolic syndrome related factors were measured to examine associations with serum dioxin and blood mercury. We also investigated associations between insulin resistance (HOMA-IR > 75th percentile), defective pancreatic β-cells function (HOMA β-cell > 75th percentile), serum dioxins and blood mercury. After adjusting for confounding factors, we found that insulin resistance increased with serum dioxins (b = 0.13, P < 0.001) and blood mercury (b = 0.01, P < 0.001). Moreover, participants with higher serum dioxins or blood mercury were at a significantly increasing risk for insulin resistance (P(trend) < 0.001). The joint highest tertile of serum dioxins and blood mercury was associated with elevated HOMA-IR at 11 times the odds of the joint lowest tertile (AOR 11.00, 95% CI: 4.87, 26.63). We hypothesize that simultaneous exposure to dioxins and mercury heightens the risk of insulin resistance more than does individual exposure.

Dioxin Exposure and Insulin Resistance in Taiwanese Living Near a Highly Contaminated Area

Background: Several epidemiologic studies suggest a slightly increased risk of type 2 diabetes in relation to background levels of dioxins. Little is known about how serum dioxins might affect insulin resistance, a hallmark of type 2 diabetes. We examined the association between exposure to dioxins and insulin resistance. Methods: We investigated 1234 nondiabetic persons living near a deserted pentachlorophenol factory. Using high-resolution gas chromatography/high-resolution mass spectrometry and blood biochemistry tests, we measured serum dioxins, fasting glucose, and insulin. Finally, we examined associations between serum dioxin levels and the homoeostasis model assessments of insulin resistance and pancreatic &bgr;-cell function. Results: Participants with insulin resistance (index at or above the 75th percentile) had higher dioxin levels (24.3 vs. 19.8 pg WHO98-TEQDF/g lipid) than those without insulin resistance. In both the crude and adjusted models, insulin resistance increased with serum polychlorinated dibenzo-p-dioxins and dibenzofuran (PCDD/F) levels. We found a slight monotonic increase in insulin resistance across the serum PCDD/F categories (P for the trend <0.001). Groups with serum dioxin levels higher than 20.5 pg WHO98-TEQDF/g lipid had higher insulin resistance (adjusted odds ratios of 2.7, 3.5, and 5.0 for 50th to <75th, 75th to <90th, and ≥90th percentile, respectively) compared with the reference group (<9.6 pg WHO98-TEQDF/g lipid [< 10th percentile]). Conclusions: After adjusting for confounding factors, we found a positive association between serum dioxins and the prevalence of insulin resistance.

Interrelationship between exposure to PCDD/Fs and hypertension in metabolic syndrome in Taiwanese living near a highly contaminated area.

Metabolic syndrome (MetS) consists of a constellation of metabolic abnormalities that confer increased risk of cardiovascular disease. There is a positive correlation between exposure to persistent organic pollutants and MetS. We examine the association between PCDD/Fs and MetS components in 1490 non-diabetic persons living near a highly dioxin-contaminated area. We used factor analysis, with a set of core variables considered central features of MetS and PCDD/Fs, to group similar risk factors. Serum PCDD/Fs were positively and significantly correlated with the number of MetS components. Four risk factors-lipidemia, blood pressure, body size, and glycemia-accounted for 72.6% of the variance in the 10 core factors, and PCDD/Fs were linked to MetS through shared correlations with high blood pressure. After adjusting for confounding factors, we found that diastolic blood pressure (β=0.018; p=0.006), glucose (β=0.013; p=0.046), and waist circumference (β=0.721; p=0.042) significantly increased with increasing serum PCDD/F levels. We found significant trends for associations between metabolic syndrome and serum low-chlorinated PCDD/Fs. The highest quintiles of 2,3,4,7,8-PeCDF, 1,2,3,6,7,8-HxCDF and 2,3,7,8-TCDD had the top three adjusted ORs (95% CI) of 3.5 (1.9-6.3), 2.9 (1.7-4.9) and 2.8 (1.6-4.9), respectively. We also found a slight monotonic relationship between serum PCDD/Fs and the prevalence of MetS, especially when the serum dioxin level was higher than 25.4pg WHO(98)-TEQ(DF)g(-1) lipid (the fourth Quintile). We hypothesize that high-dose exposure to PCDD/Fs is a blood pressure-related factor that raises MetS risk.

Abdominal Obesity and Insulin Resistance in People Exposed to Moderate-to-High Levels of Dioxin.

Obesity, a risk factor for developing metabolic complications, is a major public health problem. Abdominal obesity is strongly accompanied by a cluster of metabolic abnormalities characterized by insulin resistance. The link between persistent organic pollutants (POPs) and insulin resistance has been investigated in animal and epidemiological studies. We aimed to examine whether insulin resistance is greater in people with abdominal obesity (AO) and concomitant exposure to serum dioxins (PCDD/Fs). We conducted a cross-sectional descriptive study of 2876 participants living near a PCDD/Fs contaminated area. Seventeen 2,3,7,8-substituted PCDD/Fs congeners were measured, and then the associations between the main predictor variable, serum TEQDF-1998, abdominal obesity (AO), dependent variables, and insulin resistance were examined. Twelve of the 17 congeners, widely distributed among PCDDs, and PCDFs, had trends for associations with abdominal adiposity. In men, the highest quintiles of 1,2,3,7,8-PeCDF; 1,2,3,7,8-PeCDD; 2,3,7,8-TCDD; 2,3,7,8-TCDF; and 2,3,4,7,8-PeCDF had the top five adjusted odds ratios (AORs) + 95% confidence intervals (CIs):[4.2; 2.7–6.4], [3.6; 2.3–5.7], [3.2; 2.1–5.0], [3.0; 2.0–4.5], and [2.9; 1.9–4.7], respectively. In women, the highest quintiles of 1,2,3,4,7,8,9-HpCDF; 1,2,3,6,7,8-HxCDF; and 1,2,3,4,6,7,8-HpCDF had the top three AORs + 95% CIs:[3.0; 1.9–4.7], [2.0; 1.3–3.1], and [1.9; 1.3–2.9], respectively. After confounding factors had been adjusted for, men, but not women, with higher serum TEQDF-1998 levels or abdominal obesity had a significantly (Ptrend < 0.001) greater risk for abnormal insulin resistance. The groups with the highest joint serum TEQDF-1998 and abdominal obesity levels were associated with elevated insulin resistance at 5.0 times the odds of the groups with the lowest joint levels (AOR 5.23; 95% CI: 3.53–7.77). We hypothesize that serum TEQDF-1998 and abdominal obesity affect the association with insulin resistance in general populations.

Estimated Daily Intake and Cumulative Risk Assessment of Phthalates in the General Taiwanese after the 2011 DEHP Food Scandal

A food scandal occurred in Taiwan in 2011 because the DEHP (di-2-ethylhexyl phthalate) had been intentionally used in food products. We assessed the daily intakes (DIs) and cumulative risk of phthalates in Taiwan’s general population after the scandal. The DIs of 6 phthalates, including di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), and DEHP, were evaluated using urinary phthalate metabolites. Hazard quotients of phthalates classified as affecting the reproductive (HQrep) and hepatic (HQhep) systems were assessed using cumulative approach. The creatinine-based model showed that the highest DI values in children 7-to 12- years-old were for DEHP (males: median: 4.79 μg/kg bw/d; females: median: 2.62 μg/kg bw/d). The 95th percentile (P95) of HQrep values were all >1 in the 7- to 12-year-old and 18- to 40-year-old male groups. The P95 of HQhep values were all >1 in the 7- to 18- year-old male groups. Most of the HQrep was attributable to the HQs of DnBP and DiBP (53.9–84.7%), and DEHP contributed most to HQhep (83.1–98.6%), which reveals that DnBP, DiBP and DEHP were the main risk of phthalate exposure for Taiwanese. Taiwan’s general population is widely exposed to DnBP, DiBP and DEHP, especially for young children.

Factors influencing blood mercury levels of inhabitants living near fishing areas

Methylmercury (MeHg), a well-known neuro-toxicant, is usually emitted by industrial and other man-made activities; it is ingested with seafood and shellfish, and accumulates in the human body. The aim of this study was to compare the differences in blood levels of total mercury (T-Hg) and MeHg in residents of 4 coastal sites and 4 inland sites around Taiwan. Meanwhile, the potential question is warranted to find out the association between dietary intake and MeHg accumulation. We found that coastal residents had significantly higher mean blood T-Hg levels (mean: 16.1 μg/L, range: 0.9-184.9 μg/L) than inland residents (mean: 11.8 μg/L, range: 0.8-146.6 μg/L). The same was for blood MeHg levels: coastal residents (mean: 16.5 μg/L, range: 0.9-184.9 μg/L), inland residents (mean: 11.8 μg/L, range: 2.1-133.4 μg/L). These elevated levels were positively associated with seafood and shellfish consumption. However, the nature of their residential area may also be an important factor, because the highest T-Hg and MeHg levels were found in residents of a relatively non-industrialized area. To protect vulnerable population-especially children and pregnant women-it is important to know whether locally caught or raised and consumed fish has any source of Hg and MeHg pollution.

Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013

Background: Previous epidemiologic and toxicological studies provide some inconsistent evidence that exposure to phthalates may affect thyroid function and growth hormone homeostasis. Objective: To assess the relations between exposure to phthalates and indicators of thyroid function and growth hormone homeostasis disturbances both among adults and minors. Methods: We conducted a population‐based cross‐sectional study of 279 Taiwanese adults (≥18 years old) and 79 minors (<18 years old) in 2013. Exposure assessment was based on urinary biomarkers, 11 phthalate metabolites measured by using online liquid chromatography/tandem mass spectrometry. Indicators of thyroid function included serum levels of thyroxine (T4), free T4, triiodothyronine, thyroid‐stimulating hormone, and thyroxine‐binding globulin (TBG). Growth hormone homeostasis was measured as the serum levels of insulin‐like growth factor 1 (IGF‐1) and insulin‐like growth factor binding protein 3 (IGFBP3). We applied multivariate linear regression models to examine these associations after adjusting for covariates. Results: Among adults, serum T4 levels were negatively associated with urinary mono‐(2‐ethyl‐5‐hydroxyhexyl) phthalate (&bgr;=−0.028, P=0.043) and the sum of urinary di‐(2‐ethylhexyl) phthalate (DEHP) metabolite (&bgr;=−0.045, P=0.017) levels. Free T4 levels were negatively associated with urinary mono‐ethylhexyl phthalate (MEHP) (&bgr;=−0.013, P=0.042) and mono‐(2‐ethyl‐5‐oxohexyl) phthalate (&bgr;=−0.030, P=0.003) levels, but positively associated with urinary monoethyl phthalate (&bgr;=0.014, P=0.037) after adjustment for age, BMI, gender, urinary creatinine levels, and TBG levels. Postive associations between urinary MEHP levels and IGF‐1 levels (&bgr;=0.033, P=0.006) were observed. Among minors, free T4 was positively associated with urinary mono benzyl phthalate levels (&bgr;=0.044, P=0.001), and IGF‐1 levels were negatively associated with the sum of urinary DEHP metabolite levels (&bgr;=−0.166, P=0.041) after adjustment for significant covariance and IGFBP3. Conclusions: Our results are consistent with the hypothesis that exposure to phthalates influences thyroid function and growth hormone homeostasis. HighlightsWe measured urinary phthalate metabolites, thyroid, growth hormones in the general Taiwanese.Serum T4 and Free T4 levels were negatively associated with DEHP metabolites, among adults.Serum IGF‐1 levels were negatively associated with DEHP metabolites among minors.

Association between Dioxin and Diabetes Mellitus in an Endemic Area of Exposure in Taiwan: A Population-Based Study.

Abstract Dioxin has been recognized as an environmental endocrine disruptor, but epidemiology studies of its effects on type 2 diabetes mellitus (DM) found inconsistent results, especially in men. Therefore, we conducted a study in Taiwan to evaluate the association between exposure to dioxin and DM. We recruited participants in an area where the residents were exposed to dioxin released from a factory. Using 20 and 64 pg WHO98-TEQDF/g lipid as the cut-offs, we categorized participants into 3 groups according to the level of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the serum. We defined DM as a fasting plasma glucose level more than 126 mg/dl or an existing diagnosis. Of the 2898 participants, 425 patients of DM were identified, and we observed positive associations between dioxin and DM. After adjusting for age and body mass index (BMI), we found that a high serum dioxin level was an independent risk factor for DM (adjusted odds ratio [AOR] associated with 20–63 pg WHO98-TEQDF/g lipid = 2.1, 95% confidence interval [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 sex, the serum dioxin level remained an independent risk factor for DM in both men and women. Exposure to dioxin is a risk factor for DM, independent of age and BMI in both men and women. Therefore, screening and intervention programs should be considered in endemic areas of exposure to dioxin.

Hyperuricemia after exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans near a highly contaminated area.

Background: Hyperuricemia (too much uric acid in the blood) is the predisposing condition for gout and is associated with hypertriglyceridemia, diabetes mellitus, and coronary artery disease. Polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) cause renal toxicity and elevate uric acid. The aim of this analysis was to investigate and clarify the effect of moderate-to-high PCDD/F exposure on hyperuricemia risk. Methods: In this cross-sectional study, we recruited 1531 healthy participants living near a deserted pentachlorophenol factory. We measured serum levels of 17 2,3,7,8-substituted PCDD/Fs, and then examined associations between the main predictor variable, serum TEQDF-2005 (total PCDD/Fs 2005 World Health Organization [WHO] toxic equivalency [TEQ]), and dependent variables such as uric acid, glomerular filtration rates, and hyperuricemia risk. Results: We observed a strong monotonic inverse relationship between serum TEQDF-2005 quartiles and the estimated glomerular filtration rate after adjusting for confounding factors (Men: &bgr; were 0, −4.7, −6.2, and −14.8; Women: &bgr; were 0, −6.7, −12.9, and −21.5). In addition, we observed a suggestive positive trend between serum TEQDF-2005 quartiles and uric acid only in men after adjusting for confounding factors (Men: &bgr; were 0, 0.40, 0.36, and 0.59; Pfor trend <0.05). Men with serum TEQDF-2005 higher than the reference group’s (<7.4 pg WHO2005–TEQDF/g lipid) had a higher hyperuricemia risk after adjusting for confounding factors (25th to <50th percentile, adjusted odds ratio [AOR] = 2.20 [95% confidence interval {CI} = 1.30–3.73]; 50th to <75th percentile, AOR = 1.86 [95% CI = 1.08–3.22]; ≥75th percentile, AOR = 3.00 [95% CI = 1.69–5.31]). Conclusions: We conclude that serum TEQDF-2005 is an important determinant of serum uric acid levels and heightens the risk of hyperuricemia in general populations.

Predicting the risk of cardiovascular disease in people exposed to moderate to high levels of dioxin

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Dioxins can cause cardiovascular toxicity in experimental animals. The potential role of dioxin exposure as a preventable risk factor has attracted the attention of public health services, especially because dioxin exposure is a ubiquitous problem. We aimed to investigate and clarify the effect on CVD risk of moderate-to-high exposure to dioxins. This cross-sectional study investigated 914 residents without CVD near a deserted pentachlorophenol factory. CVD-related factors were measured to examine their associations with serum dioxin. We also investigated associations between serum dioxins and the Framingham risk score. Serum PCDD/F levels were significantly positively associated with CVD risk in both genders (Men: b=0.023, P<0.001; Women: b=0.005, P<0.001; All: b=0.013, P<0.001). After adjusting for confounding factors, participants with higher serum PCDD/F levels had a higher risk for CVD than did the reference group (serum PCDD/levels<9.8 pg WHO(98)-TEQ(DF)/g lipid) (25th to <50th percentile, adjusted odds ratio (AOR)=2.96 [95% confidence interval (CI)=1.13-7.75]; 50th to<75th percentile, AOR=3.37 [1.32-8.59]; ≥75th percentile, AOR=6.22 [2.47-15.63]). We hypothesize that accumulated dioxins heightens the cardiovascular risk.