Table 5: Some epidemiological studies on diabetes.

ExposureStudy populationRelative risk or odds ratio (95% confidence interval)aMain strengthsMain limitationsReference

Ecological studies

Dioxin TCDDMortality from diabetes in the cohort involved in the Seveso accidentOR 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 documentedOnly 13 cases[191]

Cross-sectional studies

Seventeen 2,3,7,8-polychlorinated dibenzodioxins/dibenzofuransOR for top decile of adjusted serum concentrations of dioxins: 5.1 (1.18–21.7)
Coplanar polychlorinated biphenyls 77, 81, 126 and 169Population-based study in BelgiumOR 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 biphenylsOR for top decile of adjusted serum concentrations of marker PCBs: 7.6 (1.58–36.3)

Polychlorinated biphenylsCross-sectional study on 2,245 Pregnant women from the Boston (USA) areaCompared to <2.5  𝜇 g/mL serum, OR for 2.5–<3.75  𝜇 g/mL: 2.9 (1.1–7.3);
for 3.75–<5.0 μg/mL: 4.4 (1.6–12.5)
for >5.0  𝜇 g/mL: 5.1 (1.9–13.8) ( 𝑃 t r e n d  = 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, ArkansasOR for fasting insulin level >4.5  𝜇 IU/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 = 0.03Precise 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 153OR for highest decile of serum concentration compared to not detectable: 6.8 (3.0–15.5) 𝑃 t r e n d < 0 . 0 0 1
1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxinOR for highest decile of serum concentration compared to not detectable: 2.7 (1.3–5.5) 𝑃 t r e n d = 0 . 0 0 7 No differentiation between type I and type II. Few cases in referent exposure category
1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxinOR for highest decile of serum concentration compared to not detectable: 2.1 (0.9–5.2) 𝑃 t r e n d = 0 . 0 9 4
OxychlordaneOR for highest decile of serum concentration compared to not detectable: 6.5 (2.0–21.4) 𝑃 t r e n d < 0 . 0 0 1
DDE2,016 adult participants in the National Health and Nutrition Examination Survey 1999–2002OR for highest decile of serum concentration compared to lowest quartile: 4.3 (1.8–10.2) 𝑃 t r e n d = 0 . 0 0 1 Precise measurement of personal internal exposure.
Adequate control of confounding
No differentiation between type I and type II[196]
Trans-nonachlorOR for highest decile of serum concentration compared to not detectable: 11.8 (4.4–31.3) 𝑃 t r e n d < 0 . 0 0 1 No differentiation between type I and type II. Few cases in referent exposure category.
Cumulative measureb of six organochlorinesOR for highest decile of serum concentration compared to lowest quartile: 37.7 (7.8–182) 𝑃 t r e n d < 0 . 0 0 1 No differentiation between type I and type II
Cumulative measureb of six organochlorinesOR for highest decile of serum concentration compared to second quartile: 2.7 (1.5–4.8) 𝑃 t r e n d < 0 . 0 0 1

Cumulative measurec 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). 𝑃 t r e n d < 0 . 0 0 1
Cumulative measurec 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 measurec 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 measurec 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 1OR 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 measurec 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-nonachlorOR for highest quartile of serum concentration compared to not detectable: 8.0 (2.6–24.8)Few cases in referent exposure category
Beta-hexachlorocyclohexaneOR for highest quartile of serum concentration compared to not detectable: 7.0 (2.7–18.1)

Cumulative measurec 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) 𝑃 t r e n d < 0 . 0 1 Only 12 subjects with high values for insuline resistance in lowest quartile of exposure
OxychlordaneOR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to “nondetectable”: 8.7 (2.3–33.3) 𝑃 t r e n d < 0 . 0 1 Only 8 subjects with high values for insuline resistance in referent exposure category
Trans-nonachlor749 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) 𝑃 t r e n d = 0 . 0 2 Precise measurement of personal internal exposure. Adequate control of confoundingOnly 4 subjects with high values for insuline resistance in referent exposure category[198]
p,p-dichlorodiphenyltrichloroethaneOR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to lowest quartile: 1.4 (0.5–3.7) 𝑃 t r e n d = 0 . 3 3 Only 15 subjects with high values for insuline resistance in lowest quartile of exposure
HexachlorocyclohexaneOR for HOMA-IR insuline resistance values >90th percentile for highest quartile of serum concentration compared to “nondetectable” 1.7 (0.6–5.1) 𝑃 t r e n d = 0 . 5 6 Only 15 subjects with high values for insuline resistance in referent exposure category

Polybromobiphenyl-1531,367 adults participating in the National Health and Nutrition Examination Survey 2003-2004OR for highest quartile of serum concentration compared to “nondetectable”: 1.9 (0.9–4.0). 𝑃 t r e n d = 0 . 0 1 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) metabolites221 Healthy Mexican women serving as controls in a case-control study for breast cancerOdds ratios for log transformed urinary phthalates metabolites concentration and self-reported diabetes: 1.64 (0.98–2.73). 𝑃 = 0 . 0 6 0 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) cohortOR 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, BMICorrelation weakened by Additional correction for blood lipids[202]
Trans-nonachlorOR for 2nd quartile of serum concentration compared to lowest quartile: 4.8 (1.7–13.7)Only 7 cases in lowest quartile (reference)

PCB153Nested 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, BMICorrelation weakened by additional correction for blood lipids[202]
PCB 180OR for 2nd quartile of serum concentration compared to lowest quartile: 3.4 (1.3–9.0)
PCB170OR 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-153OR for 3rd quartile of serum concentration compared to lowest quartileCorrelation 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.