• 沒有找到結果。

Increased risk of diabetes and polychlorinated biphenyls and dioxins A 24-year follow-up study of the yucheng cohort

N/A
N/A
Protected

Academic year: 2021

Share "Increased risk of diabetes and polychlorinated biphenyls and dioxins A 24-year follow-up study of the yucheng cohort"

Copied!
6
0
0

加載中.... (立即查看全文)

全文

(1)

Increased Risk of Diabetes and

Polychlorinated Biphenyls and Dioxins

A 24-year follow-up study of the Yucheng cohort

SHU-LIWANG,PHD1,2 PEI-CHIENTSAI,PHD3

CHIU-YUEHYANG,PHD3,4

YUELIANGLEONGUO,MD PHD5

OBJECTIVE — Polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans

(PC-DFs) are important and persistent organic pollutants (POPs) in humans. Recent cross-sectional studies have detected increased concentrations of serum POPs in diabetic patients. We aimed to examine the association between previous high exposures to PCBs and PCDFs and the cumu-lative incidence of type 2 diabetes and hypertension.

RESEARCH DESIGN AND METHODS — During the late 1970s, the consumption of

rice-bran oil laced with PCBs poisoned thousands of Taiwanese. Between 1993 and 2003, we examined 1,054 Yucheng (“oil disease”) victims against neighborhood reference subjects using a protocol blinded for POP exposure. Here, we report the results derived from 378 Yucheng subjects and 370 matched references.

RESULTS — The diabetes risk to members of the Yucheng cohort relative to their reference

subjects was significantly increased for women (odds ratio [OR] 2.1 [95% CI 1.1– 4.5]) but not for men after considering age, BMI, cigarette smoking, and alcohol intake. Yucheng women diagnosed with chloracne had adjusted ORs of 5.5 (95% CI 2.3–13.4) for diabetes and 3.5 (1.7–7.2) for hypertension compared with those who were chloracne free.

CONCLUSIONS — Yucheng women, who had endured previous exposure to PCBs and

PCDFs, suffered from increased incidences of diabetes, particularly those who had retained significant levels of pollutant as evident from chloracne. When planning treatments against diabetes, the body burden of PCBs and dioxins should be carefully considered, especially for women.

Diabetes Care 31:1574–1579, 2008

T

ype 2 diabetes is becoming more

prevalent throughout the world, and although a number of conven-tional risk factors have already been iden-tified, they can only partly explain such high levels of incidence. Polychlorinated biphenyls (PCBs) and dioxins are persis-tent organic pollutants (POPs) with long half-lives in the human body, and they may act as endocrine disruptors and ex-hibit endocrine system effects (1). The study of veterans of Operation Ranch

Hand reported a higher dioxin level in diabetic patients compared with nondia-betic subjects (2). Longnecker et al. (3) revealed a 30% higher level of total PCBs in diabetic (primarily type 1) pregnant women than in nondiabetic subjects re-cruited in 1959 –1966. Similar conclu-sions were drawn from the National Health and Nutrition Examination Survey (NHANES) (4) and other population studies in Belgium (5), Michigan (6), and Seveso, Italy (7). These data raised great

concerns for public health (8) and pro-moted etiological research into the bio-logical effects of POPs (9,10). Recently, the NHANES study in the U.S. showed striking dose-response relationships be-tween the prevalence of diabetes and se-rum levels of six POPs, including PCB 153, dioxins, and organochlorine pesti-cides (OCPs) (11). Interestingly, severe

obesity (BMIⱖ30 kg/m2) did not relate to

an increased diabetes risk in those with undetectable levels of POPs. The cross-sectional study findings warrant a fol-low-up cohort study to assess the long-term effects of POPs on the risk of developing diabetes and hypertension. A mass poisoning occurred in central Tai-wan after a quantity of rice-bran oil in-gested in 1978 –1979 was later found to be contaminated with PCBs and their heat-degraded byproducts (12). By the end of February 1983, there were 2,061 recorded cases of PCB poisoning, based on the symptoms and pathology of the illness, such as abnormally high levels of blood PCBs. The Yucheng (“oil disease”) cohort was estimated to have consumed an average of 1 g (range 0.77–1.84) of PCBs and 3.8 mg polychlorinated diben-zofurans (PCDFs) during an average of nine months’ exposure to the contami-nated oil. Most (83%) of the blood levels ranged from 11 to 150 ppb. The current 24-year follow-up study of the Yucheng cohort provides a good opportunity to ex-amine the hypothesis that raised levels of PCBs and dibenzofurans (DFs) might be associated with an increased risk of dia-betes. Though obese people have been en-couraged to reduce body weight by calorie restriction, serum levels of total PCBs have been shown to increase in the 6 –9 months following the weight-loss program (13). Studying the effects of POPs on the degree of risk of type 2 dia-betes is clearly relevant to managing both diabetes and obesity in modern societies. RESEARCH DESIGN AND METHODS — Beginning in 1992 and using the addresses listed for the 2,061 victims in the Yucheng registry obtained from the Taiwan Provincial Department ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●

From the1

Division of Environmental Health and Occupational Medicine, National Health Research

Insti-tutes, Miaoli, Taiwan; the2Institute of Environmental Medicine, College of Public Health, China Medical

University Hospital, Taichung, Taiwan; the3

Department of Basic Medical Sciences, National Cheng-Kung

University Medical College, Tainan, Taiwan; the4Department of Health Business Administration,

Hung-Kuang University, Taichung, Taiwan; and the5

Department of Environmental and Occupational Medi-cine, National Taiwan University College of MediMedi-cine, and National Taiwan University Hospital, Taipei, Taiwan.

Corresponding author: Yueliang Leon Guo, leonguo@ntu.edu.tw. Received 26 December 2007 and accepted 13 May 2008.

Published ahead of print at http://care.diabetesjournals.org on 16 May 2008. DOI: 10.2337/dc07-2449. © 2008 by the American Diabetes Association. Readers may use this article as long as the work is properly

cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons. org/licenses/by-nc-nd/3.0/ for details.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

P a t h o p h y s i o l o g y / C o m p l i c a t i o n s

(2)

of Health, we attempted to locate each subject’s record. Of these records, the ad-dresses were wrong for 154 subjects, which prevented us from tracing those people, and a further 70 records had to be excluded because they belonged to the children of this Yucheng cohort (Fig. 1). A total of 83 subjects (8%) were deceased, 668 (66%) were aged less than 30, and 32 (3%) had a remote address. Individuals for the background-exposed groups were recruited in 1992 and matched against the Yucheng subjects for neighborhood (the same back in 1979), sex, age (no more than 3 years’ difference), and expo-sure to POPs, such that none of the

con-trol individuals were in the original registration cohort (14). Between 1993 and 2003, we conducted a morbidity fol-low-up of the exposed subjects and their reference group with trained interviewers blinded to exposure status. Medical infor-mation on individuals who had been di-agnosed or treated by certified medical doctors was acquired by telephone. The current study focused on individuals born before 1 January 1963 so as to ex-amine the association between the cumu-lative incidence of type 2 diabetes and postnatal exposure to PCBs and PCDFs. We excluded 38 Yucheng subjects and 46 from their reference groups who were

missing data on BMI or cigarette smoking, which are important risk factors for type 2 diabetes and hypertension, respectively. After all exclusions, 378 Yucheng and 370 matched reference subjects remained for analysis within the current study. We

fo-cused on those aged⬎30 years in the

cur-rent study because type 2 diabetes is a chronic disease prevalent in the middle-aged population and because doing so prevents inclusion of subjects who could have had prenatal exposure to PCBs or PCDFs. Among the 668 subjects aged ⬍30 years, there were 90 with a matched reference subject who could be success-fully followed for a separate analysis. However, within this younger group, there were no diabetic subjects and just one hypertensive patient. We therefore omitted them from our current analysis. Body burden of dioxins and PCBs Total PCB levels were quantitated from serum samples originally collected by the Taiwan Provincial Department of Health in 1979 –1983 (12). These serum samples ranged from 0.7 to 8.2 g (average 4.5 g)

and were kept frozen at ⫺20°C before

analysis. Except for initial analyses carried out in Tokyo, all PCB levels were analyzed by the Food and Drug Bureau of the De-partment of Health Executive, Yuan, Tai-wan. A Microtek 200 gas chromatography system was fitted with an electron capture

detector (Ni63-ECD) and a glass column

(3 mm ⫻ 2 mm) packed with

Chro-mosorb WHP (80/100 mesh) coated with 3% OV-1. The temperatures of the inlet, column, and detector were maintained at 230, 200, and 280°C, respectively. The Webb-McCall method was adopted to quantify PCBs, with Kanechlor 500 used as a reference standard (15). For the back-ground-exposed reference group, serum pooled from 50 subjects was analyzed us-ing a high-resolution gas chromatogra-phy/high-resolution mass spectrometry method. Although we studied congener-specific profiles of PCBs and PCDFs in 1994 (16), we utilized information on to-tal PCB levels measured at the time of the episode for the respective dosages that re-lated to the cumulative incidence of disease.

Statistical methods

Student’s t, Mann-Whitney U (if not

nor-mally distributed), and␹2tests were used

to compare continuous and categorical variables between the exposed and refer-ence groups. A univariate logistic regres-sion model was used to calculate odds

(3)

ratios (ORs) for diabetes prevalence among the exposed, relative to reference subjects, and multivariable logistic re-gression was used to evaluate the ORs with adjustments for potential confound-ing factors. For women, we did not carry out further adjustments for cigarette smoking (with only three smokers) and alcohol intake (with only five drinkers) in deriving a reliable model. We used JMP 5.0.1 software for all the analyses (SAS Institute, Cary, NC).

RESULTS — Table 1 shows very simi-lar distributions in age, sex, BMI, educa-tion, lifestyle, and occupation between the Yucheng cohort and the background-exposed reference group. Mean PCBs in the Yucheng subjects were about 40- to 50-fold those of the reference group. Men appeared to be older than women by around 7 years. We suspected that men younger than 35 years old were too busy working to get registered for special care in 1979 –1980.

The Yucheng subjects had a very high risk of developing chloracne compared with the reference group (Table 2). The AOR (OR adjusted for age and BMI in women and age, BMI, cigarette smoking, and alcohol drinking in men) of diabetes for the Yucheng cohort relative to the ref-erence group remained significant in

women (OR 2.1; P⬍ 0.05) after adjusting

for age and BMI. We found an

age-adjusted OR of 6.4 (P⬍ 0.05) in women

aged ⬎65 years who received diabetes

therapy, which rose to 6.6 (P⬍ 0.05)

af-ter further adjustment for BMI. For both sexes, there was a slight but nonsignifi-cant increase in the risk of developing hy-pertension and cardiovascular disease. We compared the rate at which diabetes developed in subjects that exhibited chloracne with the rate in which it devel-oped in those free of chloracne and found a highly significant age-adjusted OR of 4.6 (95% CI 1.9 –11.4) and AOR of 5.5 (2.3–13.4) in women but not in men (Ta-ble 3). The same pattern was found for hypertension (AOR 3.5 [95% CI 1.7– 7.2]) and cardiovascular disease (3.0 [1.5– 8.6]).

CONCLUSIONS — We found that diabetes was twice as prevalent in Yucheng women who had been exposed to PCBs and PCDFs during the 1978 – 1979 poisoning as it was in the reference population in the long-term cohort study. The AOR significantly increased to 2.5 for those requiring therapy for diabetes and to 5.5 for those with chloracne, a condi-tion symptomatic of POP poisoning. This correlation between POPs and diabetes is consistent with the findings from cross-sectional studies in Belgium (5) and the U.S. (2,4,11,17,25). In the current study, most excess body burdens of PCBs and PCDFs were present in women with an average age of 25 years, when type 2 dia-betes most likely had not yet occurred. The cumulative incidence associated with PCB and DF exposure provides evidence

that the exposure happened before onset of diabetes. However, caution should be exercised in interpreting the data because members of the Yucheng cohort group were accidentally exposed to PCBs and PCDFs for nearly a year via a diet of con-taminated oil. These results might not ap-ply to the background population, and further investigations are needed to con-trol for the effects of different PCBs de-rived from sources other than those of the 1978 –1979 poisoning. A recent report using the NHANES data showed signifi-cant association between non– dioxin-like PCBs and increased risk of insulin resistance in nondiabetic subjects, partic-ularly those with a larger waist circumfer-ence (18). For those in the upper quartile of PCB 170 exposure, compared with the nondetectable reference group, the OR

increased to 4.1 (P ⬍ 0.01). In the

Yucheng cohort, a total of 33 PCB conge-ner profiles showed that PCB 170 consti-tuted 13% of all PCB concentrations (16). In addition to PCB 170, PCB 180 (which represented 14% of 33 PCBs), PCB 153 (13%), and PCB 156 (13%) each repre-sented over 12% of the total PCBs. This implies that certain PCB congeners might be associated with an increased risk of di-abetes occurrence.

We further report that Yucheng women diagnosed with chloracne have a significantly increased risk of developing hypertension and cardiovascular disease. This increased risk of hypertension may partly result from diabetes complications Table 1—General characteristics of the Yucheng cohort and their matched reference group aged >30 years in 1993

Men Women

Yucheng Reference group P Yucheng Reference group P

n 155 152 — 223 218 — Age in 1993 (years) 59.6⫾ 11.5 58.9⫾ 11.5 ns 52.2⫾ 10.6 51.6⫾ 10.5 ns ⬍55 62 (40.0) 63 (41.5) — 155 (69.5) 158 (72.5) — 55–64 37 (23.9) 40 (26.3) — 29 (13.0) 26 (11.9) — ⱖ65 56 (36.1) 49 (32.2) — 39 (17.5) 34 (15.6) — BMI (kg/m2) 24.1⫾ 3.1 24.0⫾ 3.1 ns 24.3⫾ 8.5 23.5⫾ 3.4 ns Education (years) 7.2⫾ 4.1 7.2⫾ 3.7 ns 6.6⫾ 4.1 7.3⫾ 4.2 ns Current smoker 85 (55.2) 93 (62.0) ns 2 (0.9) 1 (0.5) ns Alcohol drinking 41 (26.8) 34 (22.8) ns 4 (1.8) 1 (0.5) ns Occupation None 70 (45.2) 59 (38.8) ns 111 (49.8) 92 (42.2) ns Government 6 (3.9) 4 (2.6) ns 7 (3.1) 8 (3.7) ns Agriculture 12 (7.7) 23 (15.1) ns 5 (2.2) 6 (2.8) ns Manufacturing 54 (34.8) 53 (34.9) ns 69 (30.9) 75 (34.4) ns Commercial 13 (8.4) 13 (8.6) ns 31 (13.9) 37 (17.0) ns Serum PCBs (ppb) 73.3⫾ 86.3 1.67* — 87.4⫾ 151.0 1.67* —

Data are means⫾ SD or n (%). *General population had mean serum PCB levels of 1.67 ppb wet weight as previously reported using a pooled sample from 50

(4)

involving cardiovascular disease. Preva-lence of increased blood pressure was most strongly correlated with PCDFs, particularly 1,2,3,4,7,8-HxCDF in nondi-abetic subjects in the NHANES study (22). This corresponded to data in the Yucheng cohort, in which 1,2,3,4,7,8-HxCDF (toxic equivalency factor 0.1) and 2,3,4,7,8-PeCDF (toxic equivalency fac-tor 0.5) were important congeners,

con-tributing ⬃20 and 50% of the total

dioxins’ toxic equivalent quotients (TEQs), respectively (16). This suggests that congeners containing PCDF or poly-chlorinated dibenzo-dioxins might be as-sociated with an increased risk of hypertension.

The current study showed a nonsig-nificant association between PCB and DF exposure and type 2 diabetes occurrence in men, which is not consistent with find-ings of previous cross-sectional studies (11,17). In the Michigan follow-up study of the effects of exposing farmers and other households to animal feed contam-inated with PCBs, women experienced twice the incidence of self-reported type 2 diabetes when total PCBs exceeded 5 ppb, but there was no increased diabetic risk for men (6). The 20-year follow-up study of the Seveso cohort, highly exposed to tetra-chlorinated dibenzo-p-dioxin after a factory incident in 1976 (7), showed that the mortality rate from diabetes had sig-nificantly doubled for women residing in the exposure area compared with women residing in the reference area but that the relationship was not present in men. It is notable that cigarette smoking was much more prevalent in the men involved in both our study and the Michigan study compared with the women who were in-vestigated. Cigarette smoking has been found to activate the aryl-hydrocarbon re-ceptor (19), which might be associated with the accelerated excretion of PCBs. Our study also showed slightly lower mean PCB and PCDF levels in men than in women. Further, women tend to have a greater fat percentage than men, which might result in a longer half-life of these lipophilic compounds. Obesity as a risk factor for diabetes might be attributable partly to the lipophilic compounds’ stor-age in white adipose tissue (1). Fat tissue has been suggested to be a vehicle for in-creased diabetes risk (8). Women could also be more vulnerable to PCB and PCDF exposure as a result of higher estrogen levels than men. PCDFs, and some PCBs, can induce CYP1A1 and CYP1B1 gene ex-pression by serving as aryl-hydrocarbon

Table 2— Prevalence or ORs of reported diseases ever diagnosed by a physician in Yucheng, stratified by sex, in Taiwan from 1979 –2003 Men Women Yucheng Reference group OR* (95% CI) AOR Yucheng Reference group OR* (95% CI) AOR n 155 152 — — 223 218 — Chloracne 66 (42.9) 1 (0.7) 117.0 (25.1–2,087)‡ 111.5 (23.9–1,985)‡ 51 (23.0) 0 (0.0) — — Type 2 diabetes without therapy 22 (14.4) 22 (14.7) 1.0 (0.5–1.8) 1.0 (0.5–1.9) 25 (11.3) 12 (5.6) 2.2 (1.1–4.7)† 2.1 (1.1–4.5)† Aged ⬍ 55 3 (4.8) 7 (11.3) 0.4 (0.1–1.5) 0.5 (0.1–1.9) 7 (4.6) 7 (4.5) 1.0 (0.3–3.1) 1.0 (0.3–3.1) Aged 55–64 9 (25.0) 5 (12.5) 2.3 (0.7–8.3) 3.7 (0.9–17.6) 6 (20.7) 0 (0.0) — — Aged ⱖ 65 10 (18.2) 10 (20.8) 0.8 (0.3–2.2) 0.8 (0.3–2.3) 12 (30.8) 5 (14.7) 2.6 (0.8–9.1) 2.6 (0.9–9.3) Type 2 diabetes with therapy 22 (14.3) 17 (11.3) 1.3 (0.6–2.6) 1.3 (0.7–2.7) 17 (7.7) 7 (3.2) 2.5 (1.0–6.7) 2.5 (1.0–6.5)† Aged ⬍ 55 3 (4.8) 3 (4.8) 1.0 (0.2–5.7) 1.3 (0.2–7.5) 3 (2.0) 5 (3.2) 0.6 (0.1–2.5) 0.6 (0.1–2.5) Aged 55–64 9 (25.0) 5 (12.5) 2.3 (0.7–8.3) 3.7 (0.9–17.7) 3 (10.3) 0 (0.0) — — Aged ⱖ 65 10 (17.9) 9 (18.8) 0.9 (0.3–2.5) 0.9 (0.3–2.6) 11 (28.2) 2 (5.9) 6.4 (1.5–43.9)† 6.6 (1.6–45.4)† Hypertension with therapy 46 (30.0) 39 (26.0) 1.2 (0.7–2.0) 1.2 (0.7–2.0) 41 (18.5) 31 (14.4) 1.3 (0.8–2.3) 1.3 (0.8–2.2) Hypertension without therapy 40 (26.0) 31 (20.7) 1.3 (0.7–2.4) 1.3 (0.8–2.4) 29 (13.1) 21 (9.7) 1.4 (0.7–2.7) 1.4 (0.8–2.5) Cardiovascular disease 22 (14.2) 17 (11.2) 1.3 (0.6–2.6) 1.3 (0.7–2.6) 30 (11.6) 21 (9.6) 1.4 (0.8–2.6) 1.5 (0.8–2.7) Data are n (%) unless otherwise indicated. *Age adjusted. † P ⬍ 0.05; ‡ P ⬍ 0.001.

(5)

receptor agonists (19). CYP1A1 and CYP1B1 catalyze hydroxylation of the

A-ring of estradiol (E2) to form the catechol

estrogen 2- or 4-hydroxyl estradiol

(2-OH-E2or 4-OH-E2, respectively), which

may be altered by exposure to dioxins

(20). The metabolism of 4-OH-E2via

re-dox-active compounds generates free rad-icals, such as reactive semiquinone intermediates. Free radicals are known to cause increased oxidative stress, which has been associated with a range of vascu-lar pathologies, including hypertension and diabetes (21). Further investigations aimed at identifying and dissecting the various POP detoxification pathways are clearly warranted.

Dioxin-like chemicals relating to dia-betes may involve an estrogen-dependent peroxisome proliferator–activated recep-tor (PPAR) pathway (23). Tetra-chlorinated dibenzo-p-dioxin cotreating estrogens were found to upregulate insu-lin-like growth factor binding protein-1 (IGFBP-1) in MCF-7 cells via the PPAR pathway (24). These compounds may counter the effects of insulin, which downregulates IGFBP-1. Dioxins or diox-in-like chemicals may therefore disrupt glucose homeostasis.

A hypertriglycemia state, often coex-isting with hypertriglycerides, might be related to delayed degradation and/or ex-cretion of the lipophilic compounds in di-abetic patients. In addition, metabolism of PCB- and DF-related genes, such as CYP1A, CYP1B, and CYP11B (19,20), may relate to the development of chloracne and later chronic conditions of hypergly-cemia and hypertension. Further study of these genetic polymorphisms related to the effect of susceptibility is suggested.

There might be confounding factors, such as OCPs (18), which are often correlated with PCBs/DFs because of a similar exposure route in humans. None-theless, levels of 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (DDE) were slightly lower in Yucheng women

(means ⫾ SD 6,380 ⫾ 620 ppb)

com-pared with their neighborhood reference subject (8,700 in pooled serum samples [Prof. Yueliang Leon Guo, personal com-munication]). Potential confounding ef-fects from OCPs are therefore unlikely.

The effects of aging could have influ-enced this 24-year follow-up study, since members of the exposure group would be expected to die sooner from diabetes and/or cardiovascular disease. This influ-ence might be slight, as we found that only one man and six women died from

diabetes among all registered Yucheng subjects (25). Additionally, the women appeared to be younger than the men by ⬃7 years. One possibility for future study would be to select a group of younger women; this might reduce the statistical power in women because diabetes and hypertension are generally less prevalent in the younger age-group. Nonetheless, we have established the increased risk for women compared with men; thus, our study is unlikely to have a biased conclusion.

The present study did not include other disease-related lifestyle features, such as exercise and total calorie intake, which might relate to differences in per-sonal socioeconomic status and an altered risk of diabetes. We used neighborhood reference subjects as a background expo-sure group. Furthermore, BMI, educa-tion, and occupational distribution were similar between the exposed and refer-ence groups. A previous study showed that lipid contents were similar between the two groups (16). We would expect the same conclusion after adjustments for dif-ferences in lipids, exercise, and total cal-orie intake.

In conclusion, an increased cumula-tive incidence of type 2 diabetes was seen among Yucheng women who had been exposed to PCBs and PCDFs, particularly among those diagnosed with chloracne. In modern societies, the body burden of PCBs and dioxins clearly needs to be considered within the framework of di-abetes prevention. The effects of female sex and genetic factors warrant further investigation.

Acknowledgments — This study was

sup-ported by a National Taiwan University Hos-pital research grant and National Science Council Grant #96-2314-B-002-100-MY2, and the National Health Research Institutes, Taiwan, EO-096-PP-13.

References

1. Mullerova D, Kopecky J: White adipose tissue: storage and effector site for envi-ronmental pollutants. Physiol Res 56:375– 381, 2007

2. Henriksen GL, Ketchum NS, Michalek JE, Swaby JA: Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand. Epidemiology 8:252–258, 1997 3. Longnecker MP, Klebanoff MA, Brock

JW, Zhou H: Polychlorinated biphenyl se-rum levels in pregnant subjects with dia-betes. Diabetes Care 24:1099 –1101, 2001 4. Everett CJ, Frithsen IL, Diaz VA,

Koop-Table 3— Lifetime prevalence of medical conditions in Yucheng individuals without (negative) or with (positive) reported chloracne aged > 30 years, stratified by sex, in 2003 Men Women Negative Positive P OR* AOR Negative Positive P OR AOR n 95 72 — — — 186 58 — — — Age (years) 61.6 ⫾ 11.6 58.7 ⫾ 11.5 0.2 — — 52.3 ⫾ 11.4 56.9 ⫾ 9.7 0.006 — — BMI (kg/m 2 ) 24.2 ⫾ 3.0 24.2 ⫾ 3.2 1.0 — — 24.2 ⫾ 9.5 24.6 ⫾ 3.3 0.7 — — Diabetes 11 (11.6) 12 (16.9) 0.2 1.7 (0.7–4.3) 1.7 (0.7–4.6) 11 (5.9) 14 (24.1) 0.0006 4.6 (1.9–11.4)‡ 5.5 (2.3–13.4)‡ Hypertension 34 (35.8) 19 (26.4) 0.1 0.7 (0.4–1.5) 0.6 (0.3–1.1) 27 (14.4) 22 (37.9) 0.0009 3.3 (1.6–6.8)‡ 3.5 (1.7–7.2)‡ Cardiovascular disease 14 (14.7) 12 (16.7) 0.8 1.3 (0.6–3.2) 0.9 (0.4–2.2) 22 (11.8) 15 (25.9) 0.0035 2.3 (1.1–4.8)‡ 3.0 (1.5–8.6)‡ PCBs (ppb) 53.9 ⫾ 53.2 94.4 ⫾ 106.9 0.004 — — 72.6 ⫾ 114.7 121.4 ⫾ 202.8 0.04 — — Data are n (%), means ⫾ SD, or OR (95% CI). *Age adjusted. ‡ P ⬍ 0.001.

(6)

man RJ, Simpson WM Jr, Mainous AG 3rd: Association of a polychlorinated dibenzo-p-dioxin, a polychlorinated bi-phenyl, and DDT with diabetes in the 1999 –2002 National Health and Nutri-tion ExaminaNutri-tion Survey. Environ Res 103:413– 418, 2007

5. Fierens S, Mairesse H, Heilier JF, De Bur-bure C, Focant JF, Eppe G, De Pauw E, Bernard A: Dioxin/polychlorinated bi-phenyl body burden, diabetes and endo-metriosis: findings in a population-based study in Belgium. Biomarkers 8:529 –534, 2003

6. Vasiliu O, Cameron L, Gardiner J, Deguire P, Karmaus W: Polybrominated biphenyls, polychlorinated biphenyls, body weight, and incidence of adult-onset diabetes mellitus. Epidemiology 17:352– 359, 2006

7. Bertazzi PA, Consonni D, Bachetti S, Rubagotti M, Baccarelli A, Zocchetti C, Pesatori AC: Health effects of dioxin ex-posure: a 20-year mortality study. Am J Epidemiol 153:1031–1044, 2001 8. Porta M: Persistent organic pollutants and

the burden of diabetes. Lancet 368:558 – 559, 2006

9. Remillard RB, Bunce NJ: Linking dioxins to diabetes: epidemiology and biologic plausibility. Environ Health Perspect 110: 853– 858, 2002

10. Cranmer M, Louie S, Kennedy RH, Kern PA, Fonseca VA: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and in-sulin resistance. Toxicol Sci 56:431–436, 2000

11. Lee DH, Lee IK, Song K, Steffes M, To-scano W, Baker BA, Jacobs DR Jr: A strong dose-response relation between serum concentrations of persistent organic pol-lutants and diabetes: results from the Na-tional Health and Examination Survey

1999 –2002. Diabetes Care 29:1638 – 1644, 2006

12. Hsu ST, Ma CI, Hsu SK, Wu SS, Hsu NH, Yeh CC, Wu SB: Discovery and epidemi-ology of PCB poisoning in Taiwan: a four-year follow-up. Environ Health Perspect 59:5–10, 1985

13. Walford RL, Mock D, MacCallum T, La-seter JL: Physiologic changes in humans subjected to severe, selective calorie re-striction for two years in biosphere 2: health, aging, and toxicological perspec-tives. Toxicol Sci 52:61– 65, 1999 14. Guo YL, Yu ML, Hsu CC, Rogan WJ:

Chloracne, goiter, arthritis, and anemia after polychlorinated biphenyl poisoning: 14-year follow-up of the Taiwan Yucheng cohort. Environ Health Perspect 107:715– 719, 1999

15. Webb RG, McCall AC: Quantitative PCB standards for electron capture gas chro-matography. J Chromatogr Sci 11:366 – 373, 1973

16. Hsu JF, Guo YL, Yang SY, Liao PC: Con-gener profiles of PCBs and PCDD/Fs in Yucheng victims fifteen years after expo-sure to toxic rice-bran oils and their im-plications for epidemiologic studies. Chemosphere 61:1231–1243, 2005 17. Lee DH, Lee IK, Steffes M, Jacobs DR Jr:

Extended analyses of the association be-tween serum concentrations of persistent organic pollutants and diabetes. Diabetes Care 30:1596 –1598, 2007

18. Lee DH, Lee IK, Jin SH, Steffes M, Jacobs DR Jr: Association between serum con-centrations of persistent organic

pollut-ants and insulin resistance among

nondiabetic adults: results from the Na-tional Health and Nutrition Examination Survey 1999 –2002. Diabetes Care 30: 622– 628, 2007

19. Safe SH: Development validation and problems with the toxic equivalency

fac-tor approach for risk assessment of diox-ins and related compounds. J Anim Sci 76: 134 –141, 1998

20. Wang SL, Chang YC, Chao HR, Li CM, Li LA, Lin LY, Papke O: Body burdens of polychlorinated dibenzo-p-dioxins, di-benzofurans, and biphenyls and their re-lations to estrogen metabolism in preg-nant women. Environ Health Perspect 114: 740 –745, 2006

21. Ceriello A: Possible role of oxidative stress in the pathogenesis of hypertension. Dia-betes Care 31:S181–S184, 2008

22. Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr: Relationship between serum con-centrations of persistent organic pollut-ants and the prevalence of metabolic syndrome among non-diabetic adults: re-sults from the National Health and Nutri-tion ExaminaNutri-tion Survey 1999 –2002. Diabetologia 50:1841–1851, 2007 23. Hokanson R, Miller S, Hennessey M,

Flesher M, Hanneman W, Busbee D: Dis-ruption of estrogen-regulated gene ex-pression by dioxin: downregulation of a gene associated with the onset of non-in-sulin-dependent diabetes mellitus (type 2 diabetes). Hum Exp Toxicol 23:555–564, 2004

24. Marchand A, Tomkiewicz C, Marchan-deau JP, Boitier E, Barouki R, Garlatti M: 2,3,7,8-Tetrachlorodibenzo-p-dioxin in-duces insulin-like growth factor binding protein-1 gene expression and counter-acts the negative effect of insulin. Mol Pharmacol 67:444 – 452, 2005

25. Tsai PC, Ko YC, Huang W, Liu HS, Guo YL: Increased liver and lupus mortalities in 24-year follow-up of the Taiwanese people highly exposed to polychlorinated biphenyls and dibenzofurans. Sci Total Environ 374:216 –222, 2007

參考文獻

相關文件

Consistent with the negative price of systematic volatility risk found by the option pricing studies, we see lower average raw returns, CAPM alphas, and FF-3 alphas with higher

You are given the wavelength and total energy of a light pulse and asked to find the number of photons it

substance) is matter that has distinct properties and a composition that does not vary from sample

Reading Task 6: Genre Structure and Language Features. • Now let’s look at how language features (e.g. sentence patterns) are connected to the structure

- Informants: Principal, Vice-principals, curriculum leaders, English teachers, content subject teachers, students, parents.. - 12 cases could be categorised into 3 types, based

Wang, Solving pseudomonotone variational inequalities and pseudocon- vex optimization problems using the projection neural network, IEEE Transactions on Neural Networks 17

volume suppressed mass: (TeV) 2 /M P ∼ 10 −4 eV → mm range can be experimentally tested for any number of extra dimensions - Light U(1) gauge bosons: no derivative couplings. =>

Define instead the imaginary.. potential, magnetic field, lattice…) Dirac-BdG Hamiltonian:. with small, and matrix