Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

Table 5

Some epidemiological studies on diabetes.

Exposure	Study population	Relative risk or odds ratio (95% confidence interval)^a	Main strengths	Main limitations	Reference
Ecological studies
Dioxin TCDD	Mortality from diabetes in the cohort involved in the Seveso accident	OR for death from diabetes was increased in all contaminate area's.; OR in zone with substantial contamination: 1.9 (1.1–3.2)	Environmental exposure and time since exposure well documented	Only 13 cases	[191]
Cross-sectional studies
Seventeen 2,3,7,8-polychlorinated dibenzodioxins/dibenzofurans		OR for top decile of adjusted serum concentrations of dioxins: 5.1 (1.18–21.7)
Coplanar polychlorinated biphenyls 77, 81, 126 and 169	Population-based study in Belgium	OR for top decile of adjusted serum concentrations of dioxin-like PCBs 13.3 (3.31–53.2)	Precise measurement of personal internal exposure.; Adequate control of confounding	Only 9 cases	[192]
Marker polychlorinated biphenyls		OR for top decile of adjusted serum concentrations of marker PCBs: 7.6 (1.58–36.3)
Polychlorinated biphenyls	Cross-sectional study on 2,245 Pregnant women from the Boston (USA) area	Compared to <2.5 𝜇g/mL serum, OR for 2.5–<3.75 𝜇g/mL: 2.9 (1.1–7.3); for 3.75–<5.0 μg/mL: 4.4 (1.6–12.5); for >5.0 𝜇g/mL: 5.1 (1.9–13.8) (𝑃trend = 0.004)	Precise measurement of personal internal exposure.; Adequate control of confounding	Only 44 cases	[193]
2,3,7,8-Tetrachloro-; dibenzo-p-dioxin (TCDD)	Subjects in good health residing within 25 miles of Vertac/Hercules Superfund site in Jacksonville, Arkansas	OR for fasting insulin level >4.5 𝜇IU/mL for top decile TCDD serum concentration (>15 ppt) : 8.5 (1.49–49.4)	Precise measurement of personal internal exposure.; Adequate control of confounding	Limited number of subjects	[194]
2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153)	196 Swedish fishermen (median age 60 years) and their wives (median age 64 years, n = 184),	OR for an increase of 100 ng/g serum lipid: 1.16 (1.03, 1.32) P = 0.03	Precise measurement of personal internal exposure.; Adequate control of confounding	Only 22 cases of diabetes	[195]
1,1-dichloro-; 2,2-bis(p-chlorophenyl)-ethylene (p,p′-DDE)		OR for an increase of 100 ng/g lipid: 1.05 (1.01, 1.09), P = 0.006)
Polychlorinated biphenyl 153		OR for highest decile of serum concentration compared to not detectable: 6.8 (3.0–15.5) 𝑃trend<0.001
1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin		OR for highest decile of serum concentration compared to not detectable: 2.7 (1.3–5.5) 𝑃trend=0.007		No differentiation between type I and type II. Few cases in referent exposure category
1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin		OR for highest decile of serum concentration compared to not detectable: 2.1 (0.9–5.2) 𝑃trend=0.094
Oxychlordane		OR for highest decile of serum concentration compared to not detectable: 6.5 (2.0–21.4) 𝑃trend<0.001
DDE	2,016 adult participants in the National Health and Nutrition Examination Survey 1999–2002	OR for highest decile of serum concentration compared to lowest quartile: 4.3 (1.8–10.2) 𝑃trend=0.001	Precise measurement of personal internal exposure.; Adequate control of confounding	No differentiation between type I and type II	[196]
Trans-nonachlor		OR for highest decile of serum concentration compared to not detectable: 11.8 (4.4–31.3) 𝑃trend<0.001		No differentiation between type I and type II. Few cases in referent exposure category.
Cumulative measure^b of six organochlorines		OR for highest decile of serum concentration compared to lowest quartile: 37.7 (7.8–182) 𝑃trend<0.001		No differentiation between type I and type II
Cumulative measure^b of six organochlorines		OR for highest decile of serum concentration compared to second quartile: 2.7 (1.5–4.8) 𝑃trend<0.001
Cumulative measure^c of 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin,; 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, and; 1,2,3,4,6,7,8,9-octachloro-dibenzo-p-dioxin		OR for highest quartile of serum concentration compared to lowest quartile: 1.8 (1.0–3.3). 𝑃trend<0.001
Cumulative measure^c of 2,3,4,7,8-pentachlorodibenzofuran,; 1,2,3,4,7,8-hexachlorodibenzofuran and; 1,2,3,4,6,7,8-heptachloro dibenzofuran		OR for highest quartile of serum concentration compared to lowest quartile: 3.7 (2.0–7.1)
Cumulative measure^c of Dioxin-like PCBs (PCBs 74, 118, 126, 156)		OR for highest quartile of serum concentration compared to lowest quartile: 24.3 (7.0–84.5)
Cumulative measure^c of nondioxin like PCBs (PCBs 138, 153, 170, 180, 187)	1,721 participants in the National Health and Nutrition Examination Survey 1999–2002, aged ≥ 20 years 1	OR for highest quartile of serum concentration compared to lowest quartile: 6.2 (2.8–13.6)	Precise measurement of personal internal exposure.; Adequate control of confounding	Rather low number of cases in lowest quartile of exposure	[197]
Cumulative measure^c of organochlorine pesticides (p,p_-Dichlorodiphenyltrichloroethane, oxychlordane, trans-nonachlor, Beta-hexachlorocyclohexane)		OR for highest quartile of serum concentration compared to lowest quartile: 13.9 (5.0–38.7)
Trans-nonachlor		OR for highest quartile of serum concentration compared to not detectable: 8.0 (2.6–24.8)		Few cases in referent exposure category
Beta-hexachlorocyclohexane		OR for highest quartile of serum concentration compared to not detectable: 7.0 (2.7–18.1)
Cumulative measure^c for Organochlorine pesticides (Oxychlordane, Trans-nonachlor, p,p-dichlorodiphenyltrichloroethane and -Hexachlorocyclohexane)		OR for HOMA-IR insulineresistance values >90th percentile for highest quartile of serum concentration compared to lowest quartile: 7.5 (2.3–23.9) 𝑃trend<0.01		Only 12 subjects with high values for insuline resistance in lowest quartile of exposure
Oxychlordane		OR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to “nondetectable”: 8.7 (2.3–33.3) 𝑃trend<0.01		Only 8 subjects with high values for insuline resistance in referent exposure category
Trans-nonachlor	749 nondiabetic participants in the National Health and Nutrition Examination Survey 1999–2002 aged ≥ 20 years.	OR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to “nondetectable”: 5.4 (1.3–23.1) 𝑃trend=0.02	Precise measurement of personal internal exposure. Adequate control of confounding	Only 4 subjects with high values for insuline resistance in referent exposure category	[198]
p,p-dichlorodiphenyltrichloroethane		OR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to lowest quartile: 1.4 (0.5–3.7) 𝑃trend=0.33		Only 15 subjects with high values for insuline resistance in lowest quartile of exposure
Hexachlorocyclohexane		OR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to “nondetectable” 1.7 (0.6–5.1) 𝑃trend=0.56		Only 15 subjects with high values for insuline resistance in referent exposure category
Polybromobiphenyl-153	1,367 adults participating in the National Health and Nutrition Examination Survey 2003-2004	OR for highest quartile of serum concentration compared to “nondetectable”: 1.9 (0.9–4.0). 𝑃trend=0.01	Precise measurement of personal internal exposure.; Adequate control of confounding	Only 11 subjects with diabetes in referent exposure category	[199]
Sum of di(2-ethylhexyl) phthalate (DEHP) metabolites	221 Healthy Mexican women serving as controls in a case-control study for breast cancer	Odds ratios for log transformed urinary phthalates metabolites concentration and self-reported diabetes: 1.64 (0.98–2.73). 𝑃=0.060	Precise measurement of personal internal exposure.; Adequate control of confounding	Only 39 diabetes cases	[200]
CDDs + PCDFs (pg TEQ/g lipid)	1374 subjects, not occupationally exposed to dioxins, aged 15–73 years, living throughout Japan (2002–2006)	OR for highest quartile of serum concentration compared to 1st plus 2nd quartile: 2.21 (1.02–5.04)	Precise measurement of personal internal exposure.; Adequate control of confounding	No distinction between types of diabetes. Reference category includes 1st and 2nd quartiles	[201]
Dioxin-like PCBs (pg TEQ/g lipid)		OR for highest quartile of serum concentration compared to 1st plus 2nd quartile: 6.82 (2.59–20.1)
Prospective studies
Oxyclordane	Nested case-control study within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort	OR for highest quartile of serum concentration compared to lowest quartile: 2.6 (1.0–7.0)	Precise measurement of personal internal exposure. Adjusted for age, sex, race, BMI	Correlation weakened by Additional correction for blood lipids	[202]
Trans-nonachlor		OR for 2nd quartile of serum concentration compared to lowest quartile: 4.8 (1.7–13.7)		Only 7 cases in lowest quartile (reference)
PCB153	Nested case-control study within the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.	OR for 2nd quartile of serum concentration compared to lowest quartile: 2.4 (1.0–6.1)	Precise measurement of personal internal exposure. Adjusted for age, sex, race, BMI	Correlation weakened by additional correction for blood lipids	[202]
PCB 180		OR for 2nd quartile of serum concentration compared to lowest quartile: 3.4 (1.3–9.0)
PCB170		OR for 2nd quartile of serum concentration compared to lowest quartile: 2.7 (1.0–7.1)		Correlation weakened by additional correction for blood lipids
PBB-153		OR for 3rd quartile of serum concentration compared to lowest quartile		Correlation weakened by additional correction for blood lipids

^aOdds ratio's are for diabetes, except when insulin resistance is mentioned.
^bTo calculate the cumulative measure, the category number of each POP (0 assigned to the nondetectable category, and 1 through 5 assigned to successively increasing categories) was added to make the sum of POP levels (SUMPOPs), producing a value of 0–30, which was itself categorized at its 25th, 50th, 75th, and 90th percentiles, making five groups.
^cTo calculate the cumulative measure of three PCDDs, the ranks of the three PCDDs were summed, then divided into quartiles. Cumulative measures were calculated in the same way subclasses similarly for the three PCDFs, the four dioxin-like PCBs, the five nondioxin-like PCBs, and the four organochlorine pesticides.