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ORIGINAL ARTICLE
Association Between Dioxin and Metabolic Syndrome by
Age and Sex in an Endemic Area of Exposure in Taiwan
Chien-Yuan Huang,a,b Ching-Chang Lee,a,c Jung-Wei Chang,a,c Ya-Yun Cheng,a Yau-Chang Kuo,d,e
How-Ran Guo,a,d,e,f and Chen-Long Wud,e
Background: Some of the effects of dioxins seem to be different
between men and women, and exposures starting at an early age seem
to have more prominent effects. Therefore, we conducted a study in
Taiwan to evaluate the associations between exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and metabolic syndrome (MetS) starting at different ages in both sexes.
Methods: We recruited participants from an area where residents
were exposed to PCDD/Fs released from a factory and defined
serum PCDD/Fs levels ≥20 pg WHO98-TEQDF/g lipid as high
dioxin levels. MetS was defined as meeting three of the following criteria: 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.
Results: Of the 2758 participants, 785 patients with 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 that a high dioxin level was an independent
predictor for MetS (adjusted odds ratio =1.38; 95% confidence
interval = 1.11, 1.72). When we stratified the participants by gender, we found that a high dioxin level remained an independent
predictor of MetS in men, but not in women, regardless of the age
at starting exposure.
Conclusions: Exposure to PCDD/Fs was associated with MetS in
men, independent of age and age at starting exposure.
Submitted 27 February 2017; accepted 11 May 2017.
From the aDepartment of Environmental and Occupational Health, College of
Medicine, National Cheng Kung University, Tainan 704, Taiwan; bTainan
Science Park Clinic, Chi-Mei Medical Center, Tainan 744, Taiwan; cResearch Center for Environmental Trace Toxic Substances, National Cheng
Kung University, Tainan 704, Taiwan; dDepartment of Occupational and
Environmental Medicine, College of Medicine, National Cheng Kung
University, Tainan 704, Taiwan; eDepartment of Occupational and Environmental Medicine, National Cheng Kung University Hospital, Tainan
704, Taiwan; and fOccupational Safety, Health, and Medicine Research
Center, National Cheng Kung University, Tainan 704, Taiwan.
Supported by grants from Tainan City Government.
H.-R.G. and C.-L.W. contributed equally to this work.
The authors report no conflicts of interest.
Correspondence: Chen-Long Wu, Department of Occupational and Environmental Medicine, College of Medicine, National Cheng Kung University, 138
Sheng-Li Road, Tainan 70428, Taiwan. E-mail: clwu@mail.ncku.edu.tw.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 1044-3983/17/2806-0S82
DOI: 10.1097/EDE.0000000000000697
S82 | www.epidem.com
研究目的:有些戴奧辛的效應在男女性之間似乎有差異,而年
輕時的暴露似乎有較明顯的效應。因此,我們在臺灣進行一項
研究,分別探討在男女兩性身上不同年齡開始的多氯戴奧辛/呋
喃暴露與代謝症候群的相關性。
研究方法:我們由一個因工廠排放戴奧辛而遭到汙染的地
區招募居民為研究對象,將血清中戴奧辛濃度≥20 pg WHO98TEQDF/g lipid定義為高暴露。代謝症候群則定義為下列五項中
至少符合三項:空腹血糖 ≥100 mg/dl或正接受糖尿病治療、腰
圍男性≥90 cm或女性≥80 cm、三酸甘油脂 ≥150 mg/dl或因三酸
甘油脂過高正接受治療、高密度膽固醇男性<40 mg/dl
或女性<50 mg/dl、及血壓 ≥130/85 mmHg或正接受高血壓治療。
研究結果:在2,758位研究對象中,有785位罹患代謝症候群,
而高戴奧辛暴露與代謝症候群呈正相關。在校正性別、
年齡及開始暴露的年齡後,高戴奧辛暴露仍然為代謝症
候群的獨立危險因子 (校正勝算比=1.38,95%信賴區間:1.11–
1.72)。以性別分層分析,我們發現不論開始暴露的
年齡早晚,高戴奧暴露在男性是代謝症候群的獨立危險因子,
但在女性不是。.
結論:戴奧辛暴露與男性的代謝症候群有關,而此相關性獨立
於開始暴露的年齡及觀察時的年紀。
(Epidemiology 2017;28: S82–S88)
D
ioxins are widely distributed environmental contaminants that were found to be related to some metabolic
disorders such as diabetes mellitus (DM) and thyroid diseases.1–3 For example, a study of U.S. veterans who were
exposed to Agent Orange and its contaminant 2,3,7,8-­tetrach
lorodibenzo-p-dioxin (TCDD) during the Vietnam War found
higher prevalence of DM.2 Likewise, after a chemical explosion, a large population in Seveso, Italy, were exposed to
relatively pure TCDD, and a study found an excess mortality
from DM.3 In addition, a study of 158 male employees who
were exposed to TCDD in another chemical accident found
a higher frequency of thyroid disease than the comparison
population. Furthermore, polychlorinated dibenzo-p-dioxin
and dibenzofurans (PCDD/Fs) were found to be associated
with insulin resistance,4 an important mechanism of metabolic syndrome (MetS). In fact, a follow-up study of women
in Seveso found that the exposure level of TCDD was associated with the occurrence of MetS.5
Epidemiology • Volume 28, Suppl 1, October 2017
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Epidemiology • Volume 28, Suppl 1, October 2017
However, some of the endocrine disrupting effects of
dioxins seem to be different between men and women. For
example, a study in Seveso observed excess mortality from
DM in women, but not in men.3 Likewise, a follow-up of the
Yucheng (oil disease) cohort in Taiwan, who were exposed to
dioxin through ingestion of rice oil contaminated with polychlorinated biphenyls (PCBs), found an association between
the dioxin level and the occurrence of DM in women, but
not in men.6 In addition, exposures starting at an early age
seem to have more prominent effects. For example, a study
of women in Seveso found an association between the exposure level of TCDD and MetS, but only in women ≤12 years
old at the time of the accident.5 However, the study did not
include men. Therefore, we conducted a study to evaluate the
associations between dioxin exposure and MetS and to determine whether the associations are different between men and
women and whether the associations depend on the age at
starting exposure.
METHODS
Study Population
This study was carried out in the Annan District of the
Tainan City in southwestern Taiwan, where a factory produced
pentachlorophenol (PCP) between 1965 and 1979. Residents
living in the vicinity of the deserted factory were found to
have high intake of PCDD/Fs from food, especially seafood,7,8
and have an average serum PCDD/F level three times higher
than that in people living in nonpolluted areas (62.5 vs. 19.7
pg WHO98-TEQDF/g lipid).9 We recruited participants from
residents of the exposure area, which covers three of the 51
administrative subdivisions (called “Li” in Taiwan) of the
Annan District: Hsien-Gong, Lu-Erh, and Ssu-Tsao. All the
residents above 18 years old were invited to participate, and
2,898 have complete measurements of serum PCDD/Fs levels, which were made by the Tainan city government between
2005 and 2007 using isotope dilution high-resolution gas chromatography/high-resolution mass spectrometry. The detailed
methodology of the measurements has been described in
previous reports.4,8,9 The study protocol was approved by the
Human Experiment and Ethics Committee of National Cheng
Kung University Hospital.
Definitions of Exposure and Outcome
Previous studies have shown that the serum PCDD/Fs
level in the general population of Taiwan typically ranged
from 15 to 20 pg WHO98-TEQDF/g lipid,10 and therefore,
we defined a “high dioxin level” as serum PCDD/Fs ≥20 pg
WHO98-TEQDF/g lipid.
In addition to the measurement of serum PCDD/Fs levels,
a health examination was offered to each participant. According to the results, we defined MetS as meeting three of the
following criteria: fasting glucose ≥100 mg/dl or under treatment for DM, waist circumference ≥90 cm in men or ≥80 cm
in women, triglycerides ≥150 mg/dl or under drug treatment
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
Dioxin and Metabolic Syndrome
for elevated triglycerides, high-density lipoprotein (HDL)
<40 mg/dl in men or <50 mg/dl in women, and blood pressures
≥130/85 mmHg or under treatment for hypertension. The criteria are implemented by the Taiwan government in concordance
with the newly developed harmonized definition of MetS,11,12
including the use of “population- and country-specific definitions” for “elevated waist circumference.” Furthermore, we
defined DM as having fasting blood sugar >126 mg/dl or under
treatment of DM and defined hypertension as having blood
pressures ≥140/90 mmHg or under treatment of hypertension.
To control effects of potential confounders, we collected data
on demographic characteristics through a self-administrated
questionnaire. In addition to medical history, participants were
also asked to provide residential history.
Data Analysis
To evaluate the effects of potential risk factors for MetS,
we performed univariate logistic regressions. In addition, we
performed multiple logistic regressions and included all predictors identified from the univariate logistic regressions in
the models to identify independent predictors of MetS and
evaluate their effects.
To assess the possible differences in the effects on men
and women, we conducted separate analyses by sex. Likewise,
to assess the possible differences in the effects introduced by the
age at starting exposure, we conducted separate analyses using
12 years old as the cutoff according to a study in Seveso, Italy.5
The age before 12 is generally considered as before puberty
in most countries, and the hypothalamic-pituitary-thyroid axis
is known to be particularly sensitive to endocrine modulation
before puberty.13 Therefore, there are biological bases for using
12 years old as the cutoff. We conducted all the data analyses
using SPSS version 15.0 (SPSS Inc., Chicago, IL).
RESULTS
Of the 2898 participants who had measurement data on
dioxin levels, 2,758 (90.9%) had completed the health examination and provided sufficient information on other potential
predictors of MetS. Of them, 1,428 had high dioxin levels, and
they were more likely to be women and older, have MetS, DM,
and hypertension, and were exposed starting after 12 years old
(Table 1).
A total of 785 participants fit the diagnostic criteria of
MetS. The risks of MetS, DM, and hypertension increased
with age in both sexes (Table 3). In those below 65 years old,
men generally had higher incidence rates of those diseases.
However, in those who were older, men had a lower incidence rate of MetS, while they had similar rates of DM and
hypertension (Table 2). In comparison with those who did not
have MetS, men were more likely to have a high dioxin level
(18.8% vs. 39.2%), be older, and start having exposure after
12 years old (20.6% vs. 45.8%) (Table 3).
In the univariate logistic regression analyses, we found
that a high dioxin level was associated with an OR of 2.79
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Epidemiology • Volume 28, Suppl 1, October 2017
Huang et al.
TABLE 1. Comparisons Between Participants With and
Without a High Dioxin Level
TABLE 3. Comparisons Between Participants With and
Without Metabolic Syndromea
PCDD/Fs (pg WHO98TEQDF/g Lipid)
Variables
Sex
Men
Women
Age, year
<40
40–64
≥65
Metabolic syndromea
No
Yes
Diabetes mellitusb
No
Yes
Hypertensionc
No
Yes
Age at starting exposure, year
≤12
>12
<20, N (%)
≥20, N (%)
870 (56.3)
601 (44.5)
676 (43.7)
751 (55.5)
972 (86.5)
429 (36.1)
70 (11.9)
152 (13.5)
759 (63.9)
516 (88.1)
1,179 (59.8)
273 (34.8)
794 (40.2)
512 (65.2)
1,385 (56.0)
86 (20.2)
1,088 (44.0)
339 (79.8)
1,063 (63.9)
406 (33.0)
601 (36.1)
823 (67.0)
1,345 (68.5)
126 (13.5)
618 (31.5)
809 (86.5)
a
Defined as meeting three of the following criteria: 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 hypertensive; data not available on 140 participants without a high dioxin level.
b
Defined as fasting glucose >126 mg/dL or under treatment for diabetes.
c
Defined as having blood pressures ≥140/90 mmHg or under treatment for
hypertension.
TABLE 2. Distributions of Age, Metabolic Syndrome,
Diabetes Mellitus, and Hypertension in Men and Women
Age, year
<40
40–64
≥65
Outcome
Metabolic syndrome
<40
40–64
≥65
Hypertension
<40
40–64
≥65
Diabetes mellitus
<40
40–64
≥65
S84 | www.epidem.com
Men, N (%)
Women, N (%)
585 (40.3)
595 (40.9)
273 (18.8)
535 (41.0)
494 (37.9)
276 (21.1)
103 (17.6)
224 (37.6)
104 (38.1)
45 (8.4)
152 (30.8)
157 (56.9)
151 (25.8)
282 (47.4)
224 (82.1)
59 (11.0)
220 (44.5)
226 (81.9)
26 (4.4)
105 (17.6)
84 (30.8)
15 (2.8)
73 (14.8)
96 (34.8)
PCDD/Fs (pg
WHO98TEQDF/g lipid)
<20
≥20
Sex
Men
Women
Age, year
<40
40–64
≥65
Age at starting
exposure, year
≤12
>12
Without Metabolic
Syndrome, N (%)
With Metabolic
Syndrome, N (%)
1,179 (81.2)
794 (60.8)
273 (18.8)
512 (39.2)
1,022 (70.3)
951 (72.9)
431 (29.7)
354 (27.1)
972 (86.8)
713 (65.5)
288 (52.5)
148 (13.2)
376 (34.5)
261 (47.5)
1,508 (79.4)
465 (54.2)
392 (20.6)
393 (45.8)
a
Defined as meeting three of the following criteria: 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, HDL <40 mg/dL
in men or <50 mg/dL in women, and blood pressures ≥130/85 mmHg or under treatment
for hypertensive; data not available on 140 participants without high dioxin levels.
(95% CI = 2.34, 3.31), and sex, age, and age when exposure
started were predictors of MetS (Table 4). Therefore, the multivariate model included high dioxin level (PCDD/Fs, ≥20 pg
WHO98-TEQDF/g lipid), sex, age (<40, 40–64, and ≥65), and
older exposure age (age at starting exposure, >12 years). After
adjusting for other predictors in the multiple logistic regressions, we found that a high dioxin level was an independent
predictor of MetS, with an AOR of 1.38 (95% CI = 1.11, 1.72).
Sex, age, and age at starting exposure were all also independent predictors of MetS (Table 4).
In the stratified analyses by sex, the models included
high dioxin level (PCDD/Fs, ≥20 pg WHO98-TEQDF/g lipid),
age (<40, 40–64, and ≥65), and older exposure age (age at
starting exposure, >12 years). We found that a high dioxin
level was associated with MetS in men (AOR = 1.59; 95%
CI = 1.22, 2.08) (Table 5). But in women, a high dioxin level
was not associated with MetS (AOR = 1.16; 95% CI = 0.80,
1.68). In both men and women, age and age at starting exposure were predictors of MetS, independent of the dioxin level
(Table 5). We performed the Omnibus test and the Hosmer–
Lemeshow test for the goodness-of-fit of the multivariate
models and found that the models had good fit. When we
stratified the population further by the age at starting exposure, the multivariate models that included high dioxin level
(PCDD/Fs, ≥20 pg WHO98-TEQDF/g lipid), sex, and age (<40,
40–64, and ≥65) showed that a high dioxin level remained to
be a predictor of MetS in men (AOR = 1.59; 95% CI = 1.22,
2.08), but not in women (data not shown in tables).
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Epidemiology • Volume 28, Suppl 1, October 2017
TABLE 4. The Predictors of Metabolic Syndrome
Univariate
Analyses
OR (95% CI)
Variables
PCDD/Fs (pg WHO98-TEQDF/g
lipid)
<20
≥20
Sex
Women
Men
Age, year
<40
40–64
≥65
Age at starting exposure, year
≤12
>12
Multivariate
Analyses
AOR (95% CI)
Reference
Reference
2.79 (2.34, 3.31) 1.38 (1.11, 1.72)
Reference
Reference
1.13 (0.96, 1.34) 1.22 (1.02, 1.46)
Reference
Reference
3.46 (2.79, 4.29) 2.61 (2.04, 3.34)
5.95 (4.68, 7.57) 3.13 (2.15, 4.56)
Reference
Reference
3.25 (2.73, 3.87) 1.51 (1.15, 1.99)
The full model included PCDD/Fs, sex, age, and age at starting exposure.
AOR indicates adjusted odds ratio; CI, confidence interval; OR, odds ratio.
TABLE 5. Predictors of Metabolic Syndrome by Sex
PCDD/Fs (pg
WHO98-TEQDF/g lipid)
<20
≥20
Age, year
<40
40–64
≥65
Age at starting
exposure, year
≤12
>12
Men
AOR (95% CI)
Women
AOR (95% CI)
Reference
1.59 (1.22, 2.08)
Reference
1.16 (0.80, 1.68)
Reference
2.30 (1.70, 3.12)
2.05 (1.24, 3.40)
Reference
3.66 (2.37, 5.65)
5.86 (3.21, 10.71)
Reference
3.63 (2.81, 4.70)
Reference
2.59 (1.70, 3.93)
The model included PCDD/Fs, age, and age at starting exposure.
AOR indicates adjusted odds ratio; CI, confidence interval.
DISCUSSION
In this study, we found that a high dioxin level was a predictor of MetS in men, independent of age, sex, and age at starting exposure. Combining “metabolic syndrome” and “dioxin”
as keywords to search literature indexed in the PubMed, we
identified 30 articles, of which six were original articles on
epidemiology studies. Of the six articles, four had data on
dioxins and MetS, but some were on the same population
(Table 6).5,14–16 The Seveso Women’s Study found that MetS
was related to a 10-fold increase in TCDD in women ≤12 years
old at starting exposure (AOR = 2.03; 95% CI = 1.25, 3.30),
but not in those who started exposure after 12 years old.5 The
other three cross-sectional studies also observed associations
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
Dioxin and Metabolic Syndrome
between exposures to certain types of dioxins and MetS.14–16
In particular, a study in Japan found positive associations with
MetS for both polychlorinated dibenzo-p-dioxins (PCDDs)
and polychlorinated dibenzofurans (PCDFs),16 which is compatible with our findings. However, those studies did not evaluate the differences in effects by sex or age at starting exposure.
Most toxic effects of dioxins and dioxin-like PCB congeners are mainly mediated by the aryl hydrocarbon receptor (AhR),
and this is also a possible mechanism through which dioxins
cause MetS.17 Dioxin can activate the AhR and then suppress the
function of peroxisome proliferator-activated receptor (PPAR) γ,
which may lead to insulin resistance.18 PPARs are ligand-activated transcription factors that control lipid metabolism and
promote differentiation of adipocytes and translation of the glucose transporter protein 4 (GLUT4).19,20 Dioxins may progressively lower the translation of GLUT4 and then cause metabolic
effect like insulin resistance and hyperglycemia. In addition to the
association between PCDD/Fs and insulin resistance observed
in humans,4 an animal study found that low-dose human serum
AhR ligands can reduce the function of mitochondria in tissues
by significant increases in TCDD, leading to weight gain, glucose
intolerance, and other components of MetS.21
MetS is highly related to age. A study of MetS in the U.S.
adult found that the prevalence increased from 6.7% in the
20–29-year-old group to 43.5% in the 60–69-year-old group.22
Another study in the United States using National Health and
Nutrition Examination Survey (NHANES) 1999–2002 data
also found that the prevalence of MetS increased from 18.9%
in the 20–39-year-old group to 39% in the 40–59-year-old
group and 54.8% in the >60-year-old group.23 In a study in
Europe, the prevalence of MetS was found to increase with
age in both men (13.2% in the 30–39-year-old group to 44.5%
in the 70–74-year-old group, and 39.4% in the 75–89-yearold group) and women (10.3% in the 30–39-year-old group to
58.4% in the 75–89-year-old group).24 In a study in China, the
prevalence of MetS increased from 39% in the 20–39-year-old
group to 68.2% in the >60-year-old group.25 In the Nutrition
and Health Survey in Taiwan (NAHSIT), the prevalence of
MetS in the study cohort elevated from 13.6% in 1993–1996
to 25.5% in 2005–2008.26 In each individual survey period,
the prevalence increased from 4% in the 19–30-year-old group
to 48.7% in the ≥65-year-old group in the 1993–1996 NAHSIT and from 6.4% in the 19–30-year-old group to 62.5% in
the age ≥65-year-old group in the 2005–2008 NAHSIT. Our
study found that the prevalence increased from 13.2% in the
<40-year-old group to 34.6% in the 40–64-year-old group and
47.5% in the >65-year-old group, and the findings are compatible with those in the previous studies. In the multiple logistic regression analyses, we found that the risk of developing
MetS increased with age, which is compatible with the findings in previous studies.
In our study population, there were more women in the
high exposure group. Dioxin is highly lipophilic, and because
women generally have more adipose tissue than men, they are
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Epidemiology • Volume 28, Suppl 1, October 2017
Huang et al.
TABLE 6. Summary of Epidemiology Studies on Dioxin and Metabolic Syndrome
Study (Country)
Chemicals (Unit)
Warner et al5 (Italy)
Lee et al14 (United States)
Uemura et al16 (Japan)
Chang et al15 (Taiwan)
TCDD (ppt; a 10-fold
increase)
HPcDD, OCDD
(by quartiles)
PCDDs, PCDFs (pg
WHO-TEQ/g lipid)
PCDD/Fs (pg WHOTEQ/g lipid)
Population, Study Design
Seveso Women’s Study,
Cohort
NHANES 1999–2002,
Cross-sectional
General inhabitants,
Cross-sectional
Residents in contaminated,
Cross-sectional
Adjusted Odds Ratio (95% CI)
By age at starting exposure: ≤12 years: 2.03 (1.25, 3.30);
>12 years: 0.96 (0.68, 1.10)
D03
Q1: 0.8 (0.5, 1.5); Q2: 1.0 (0.6, 1.7); Q3: 1.4 (0.8, 2.3);
Q4: 0.6 (0.3, 1.1)
D05
Q1: 1.5 (0.7, 3.0); Q2: 2.0 (1.0, 4.0); Q3: 1.5 (0.7, 3.1);
Q4: 2.0 (0.9, 4.1)
D07
Q1: 1.3 (0.7, 2.3); Q2: 1.6 (0.9, 2.9); Q3: 1.1 (0.6, 2.1);
Q4: 1.3 (0.7, 2.5)
F03
Q1: 1.7 (1.0, 3.0); Q2: 1.4 (0.8, 2.4); Q3: 1.4 (0.8, 2.6);
Q4: 1.0 (0.5, 1.8)
F04
Q1: 1.6 (0.9, 2.8); Q2: 1.9 (1.1, 3.4); Q3: 2.1 (1.2, 3.8);
Q4: 2.0 (1.1, 3.6)
F08
Q1: 1.2 (0.7, 2.1); Q2: 0.9 (0.5, 1.6); Q3: 1.1 (0.6, 2.0);
Q4: 1.0 (0.6, 1.7)
PCDDs
4.60–7.39: 2.2 (1.2, 4.4); 7.39–11.20: 2.1 (1.1, 4.3);
≥11.20: 3.2 (1.6, 6.7)
PCDFs
2.90–4.50: 4.0 (1.9, 9.3); 4.50–6.80: 4.1 (1.9, 9.7); ≥6.80:
4.4 (2.0, 1.1)
Quintile 1 as the reference; quintile 2: 1.3 (0.8, 2.2);
quintile 3: 1.2 (0.7, 2.0); quintile 4: 2.2 (1.3, 3.7); quintile
5: 2.3 (1.3, 3.9)
CI indicates confidence interval; HPcDD, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin; OCDD, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin.
more likely to accumulate dioxin in their bodies. In a study
in Seveso, the association between the serum dioxin level
and DM was observed in women, but not in men.3 But, we
found an association between dioxin with MetS in men, not
in women. In addition to the fact that DM is only one of the
five components of MetS and that there are factors that may
affect mortality other than incidence of DM, in the Seveso
study, no case was observed in the high exposure group, with
an expected value of only 0.6. Therefore, the lack of study
power might also contribute the difference in the findings.
We found that men had a higher risk of MetS than
women, after adjusting for age and dioxin exposure. This
finding is compatible with those in previous studies in Taiwan. A population-based survey found a prevalence rate of
20.4% in men, while it was only 15.3% in women, and the
prevalent age of MetS appeared to be earlier in men (51.3 vs.
56.2 years old).27 Another study of MetS with abdominal obesity in a Chinese population found that the age-standardized
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prevalence of men was higher (73.7% vs. 36.9%).24 But, in
a study of adults in the United States, no differences in agestandardized prevalence were found between men and women
(24.0% vs. 23.4%).22 Further studies need to explore the differences in findings observed across countries.
In the Seveso Women’s Study, an association between
the TCDD exposure level and MetS was observed, but only
in those who were <12 years old at exposure.5 However, we
did not observe an association between the PCDD/Fs exposure level and MetS in either age group in women. In addition to the fact that PCDD/Fs and TCDD might have different
effects on MetS, in the Seveso Women’s’ Study, there were
only 16 cases with an age of 12 years old or younger at starting exposure, but there were 130 in the current study. A small
number of cases is more likely to generate unreliable risk estimates, which can lead to not only underestimation, but also
overestimation as well. In fact, when the components of MetS
were examined individually in the Seveso Women’s Study, the
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Epidemiology • Volume 28, Suppl 1, October 2017
AORs ranged from 0.63 to 1.45, but the AOR associated with
MetS was as high as 2.03. Nonetheless, further studies are
needed to evaluate the difference in the effects between men
and women.
Our study had some limitations. In particular, we used a
one-time measurement of dioxin level in the blood as the exposure indicator and did not have exact data on the cumulative
exposure dose. However, because PCDD/Fs have a long halflife in the serum, 7 years28,29 or longer,30,31 and the environmental sources of the contamination remained similar during the
study period, we believe the level should have remained similar
in the participants over the years. In fact, from our review of
literature, we found that most of the previous studies on the
health effects of dioxin also had only one measurement over
the study period. On the other hand, our study has some unique
features in comparison with previous studies. With a large
population and a large number of MetS patients, we could
obtain more reliable estimates of the risks and conduct stratified analyses. Specifically, stratifications by sex and the age at
starting exposure were performed, which can help evaluate the
possible effect modifications of these factors. In addition, with
the actual measurement of the dioxin level on each participant
in such a large population, we could obtain more accurate estimates of the risks than the previous studies.
CONCLUSIONS
A high serum dioxin level is a predictor of MetS in men,
independent of age and age at starting exposure, but not in
women. Age at starting exposure and sex are also predictors
of MetS in both men and women. Therefore, screening and
intervention programs should be considered in endemic areas
of exposure to dioxin.
ACKNOWLEDGMENTS
We would like to thank the colleagues in the Department
of Environmental and Occupational Health and the Research
Center for Environmental Trace Toxic Substances of the
National Cheng Kung University as well as the Tainan City
Government for helping us completing this study.
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